Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Have any approved or investigational anti-cancer therapy, including chemotherapy or hormonal therapy, with exceptions: Hormone-replacement therapy or oral contraceptives

Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), having received at least 1 prior line of systemic therapy, and received no more than 2 prior lines of therapy in the metastatic setting (disease recurrence < 6 months from the last dose of adjuvant therapy in resected patients will be considered the first line of therapy)\r\n* Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of vater cancers

Patients with prior anthracycline therapy will be excluded

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment

Previous therapy with at least radiotherapy and temozolomide

Patients may have received prior therapy for the treatment of MDS, including but not limited to: growth factor, transfusion support, immunomodulatory (IMID) therapy, DNA hypomethylating therapy, or cytotoxic chemotherapy prior to enrollment.

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Other anticancer or experimental therapy; no other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-vascular endothelial growth factor [VEGF]/fetal liver kinase 1 [Flk-1] monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery

Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

INCLUSION CRITERIA\n\n          -  Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx,\n             hypopharynx, or larynx\n\n          -  HPV negative disease, Stage III, IVa, IVb; non-oropharyngeal HPV positive disease\n             Stage III, IVa, IVb, HPV positive oropharyngeal disease T4 or N2c or N3\n\n          -  No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative\n             intent.\n\n          -  Available tumor samples for submission or willing to undergo further tumor biopsies:\n\n          -  Age ?18 years (?19 in Korea;20 years in Japan and Taiwan).\n\n          -  ECOG Performance Status 0 or 1\n\n          -  Adequate bone marrow function\n\n          -  Adequate renal function\n\n          -  Adequate liver function\n\n          -  Pregnancy test (for patients of childbearing potential) negative at screening\n\n        EXCLUSION CRITERIA\n\n          -  Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti\n             CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically\n             targeting T cell co stimulation or immune checkpoint pathways.\n\n          -  Major surgery 4 weeks prior to randomization.\n\n          -  Prior malignancy requiring tumor-directed therapy within the last 2 years prior to\n             enrollment, or concurrent malignancy associated with clinical instability. Exceptions\n             for disease within the 2 years are superficial esophageal cancer (TIS or T1a) fully\n             resected by endoscopy, prostate cancer (Gleason score 6) either curatively treated or\n             deemed to not require treatment, ductal IS carcinoma of the breast that has completed\n             curative treatment, adequately treated basal cell or squamous cell skin cancer.\n\n          -  Active autoimmune disease\n\n          -  Any of the following in the 6 months prior to randomization: myocardial infarction,\n             severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic\n             congestive heart failure, cerebrovascular accident, transient ischemic attack, or\n             symptomatic pulmonary embolism.\n\n          -  Active infection requiring systemic therapy.\n\n          -  Use of immunosuppressive medication at time of randomization\n\n          -  Prior organ transplantation including allogenic stem-cell transplantation.\n\n          -  Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or\n             acquired immunodeficiency syndrome (AIDS) related illness.\n\n          -  Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection\n\n          -  Vaccination within 4 weeks prior to randomization.\n\n          -  Current use of or anticipated need for treatment with other anti-cancer drugs.\n\n          -  Pregnant female patients, breastfeeding female patients, and male patients able to\n             father children and female patients of childbearing potential who are unwilling or\n             unable to use 2 highly effective methods of contraception as outlined in the protocol\n             for the duration of the study and for at least 6 months after the last dose of\n             cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).

Documented disease progression after at least 1 line of prior systemic therapy.

Subjects with certain mutations that have not been treated with a targeted therapy prior to enrollment

Patients with hormone receptor positive breast cancer as defined above must plan to receive at least 5 years of adjuvant hormonal therapy in the form of tamoxifen or an aromatase inhibitor, alone or in combination with ovarian suppression; (NOTE: for patients with ER and PR staining in less than 5% of cells, hormonal therapy for at least 5 years is strongly recommended but not required); hormonal therapy can be initiated prior to or during protocol therapy

Prior adjuvant treatment with chemotherapy and/or endocrine therapy, as determined by the treating physician, is allowed; the last dose of chemotherapy or radiation therapy must be at least 30 days prior to study registration; concurrent hormonal therapy will be allowed

Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization

Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, or trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen); therapy must be Food and Drug Administration (FDA)-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an Institutional Review Board (IRB)-approved clinical trial

Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation, excluding RANKL inhibitors and bisphosphonates); in event patient recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; any planned radiation therapy must be completed before enrollment onto S1609

Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry

Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization

Patients must not be planning to require any additional form of systemic anti-tumor therapy while on protocol treatment

Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration

Prior malignancy is allowed providing it does not require concurrent therapy\r\n* Exception: active hormonal therapy is allowed

No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current colon cancer except for one cycle of mFOLFOX6

Patients must have had no prior systemic therapy

Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol; however, patients receiving extended adjuvant endocrine therapy for an earlier ER positive breast cancer treated with curative intent and without recurrence for at least 5 years may continue with their endocrine therapy

Patients who have had systemic anticancer therapy (e.g., chemotherapy, targeted therapy) within 3 weeks prior to entering the study

Patients taking bisphosphonate therapy for symptomatic hypercalcemia within the past 28 days; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have resolved any serious infectious complications related to therapy

CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Any significant medical complications related to therapy must have resolved

No treatment with chemotherapy, radiation therapy, immunotherapy, biological therapy, hormonal therapy, or other thiazolidinediones (TZDs) =< 21 days before study registration

Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status

Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed; however, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended

Children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol, with the exception of cytarabine for the treatment of TMD

1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)

Prior bevacizumab therapy is excluded.

Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this protocol

Patients must be registered within 365 days of the initial metastatic breast cancer diagnosis; first-line standard systemic therapy (chemotherapy, anti-endocrine therapy, anti-HER2, or other standard targeted therapy) for metastatic breast cancer must be given or planned to be given; if given before study entry, it cannot have exceeded a duration of 12 months at the time of registration (Note: sequencing of ablative therapy [surgery or SBRT] relative to systemic therapy, for patients randomized to Arm 2, is at the discretion of the treating physician)

Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, intravesical chemotherapy, surgery, or other therapy while on this protocol

Patients must not be planning to receive concomitant biologic therapy, hormonal therapy, chemotherapy, surgery, or other cancer therapy while on study

Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; systemic chemotherapy must begin within 72 hours of this intrathecal therapy

Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).

Patients taking bisphosphonate therapy for symptomatic hypercalcemia are NOT allowed; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible

Prior anticancer systemic therapy

Persistence of clinically relevant therapy related toxicity from previous anti-cancer therapy

Patients on long term (> 6 months) anti-androgen therapy (e.g., flutamide, bicalutamide, nilutamide) will need to be off anti-androgen for 4 weeks (wash out period) and show evidence of disease progression off the anti-androgen; patients that have been on an anti-androgen 6 months or less will need to discontinue anti-androgen therapy prior to treatment start (no wash out period required)

Prior exposure to enzalutamide or other investigational AR directed therapy

Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration

INCLUSION CRITERIA:\n\n          1. ECOG performance status ? 2.\n\n          2. Histopathologically or cytologically confirmed NSCLC.\n\n          3. Disease progression during or after treatment with one or two treatment regimen(s)\n             Treatment regimens can be chemotherapy, targeted therapy, biological therapy, or\n             immunotherapy for advanced (Stage IIIB) or metastatic disease (Stage IV). Modification\n             of a regimen to manage toxicity with a different drug does not constitute a new\n             regimen. Maintenance therapy following platinum-based chemotherapy is not considered\n             as a separate regimen. Adjuvant or neoadjuvant chemotherapy and/or chemo-radiation for\n             early stage disease do not count as prior systemic therapy. Prior radiation therapy is\n             not exclusionary. Prior immunotherapy with a PD-1/PD-L1 inhibitor is not exclusionary.\n             Prior treatment for advanced or metastatic disease must have included a platinum-based\n             regimen. (Treatment of early stage disease [Stage IIIA or earlier] with a\n             platinum-containing therapy does not count).\n\n          4. At least 1 lesion ?10 mm in longest diameter in lung parenchyma.\n\n          5. patients with nonsquamous NSCLC must have been tested for EGFR exon 19 deletion and\n             Exon 21 L858R substitution mutation. Only patients without EGFR sensitizing mutations\n             are eligible, and they must have progressed on platinum-based chemotherapy. Patients\n             with known ALK-rearrangements should be treated with an appropriate tyrosine kinase\n             inhibitor (TKI) before entering the study. The TKI regimen would count as a line of\n             treatment\n\n          6. Patients with active brain metastasis or leptomeningeal involvement with brain\n             metastases who are asymptomatic, and whose lesions by imaging are at least stable and\n             without interim development of new lesions for at least 4 weeks may be enrolled.\n\n          7. All AE's of prior systemic therapy, surgery, or radiotherapy, must have resolved to\n             CTCAE v 4.03 Grade ?2, except for neurological AE's that must have resolved to Grade\n             ?1.\n\n          8. The following laboratory results ?14 days prior to study drug admin:\n\n             Hgb ?9 g/dL independent of transfusion or growth factor support; absolute neutrophil\n             count 1.5x10^9/L independent of growth factor support; platelet count ?100x10^9/L\n             independent of transfusion or growth factor support; Serum total bilirubin ? ULN,\n             unless the patient has a diagnosis of Gilbert's disease then serum bilirubin 3.0 times\n             ULN;\n\n          9. AST & ALT ?2.5 x ULN(?1.5 x ULN if alkaline phosphatase is > 2.5 x ULN), and serum\n             creatinine ?1.5 x ULN.\n\n         10. Life expectancy >12 weeks.\n\n         11. Female patients of childbearing potential have a negative pregnancy test at baseline.\n\n         12. Signed informed consent.\n\n        EXCLUSION CRITERIA: Patients with any of the following:\n\n          1. Administration of chemo, biological, immunotherapy, radiotherapy or investigational\n             agent (therapeutic or diagnostic) ?3 weeks prior to receipt of study medication. Major\n             surgery, other than diagnostic surgery, ?4 weeks before first study drug admin.\n\n          2. Significant cardiac history:\n\n             History of myocardial infarction or ischemic heart disease ?1 year before 1st study\n             drug administration; uncontrolled arrhythmia; history of congenital QT prolongation;\n             ECG findings consistent with acute ischemic heart disease; NYHA Class III-IV cardiac\n             disease; & uncontrolled hypertension: BP consistently >150 mm Hg systolic & 100 mm Hg\n             diastolic in spite of antihypertensive medication\n\n          3. Patients who have received prior treatment with docetaxel.\n\n          4. Prior transient ischemic attack or cerebrovascular accident with in the past year.\n             Neurologic toxicities ?Grade 2 within 3 weeks of randomization.\n\n          5. History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled\n             peptic ulcer disease. (Concomitant therapy with ranitidine or its equivalent and/or\n             omeprazole or its equivalent is acceptable.) History of ileus or other significant\n             gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.\n\n          6. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.\n\n          7. Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or\n             C.\n\n          8. Known prior hypersensitivity reaction to any product containing polysorbate 80,\n             Polyoxyethylene 15 hydroxystearate/Macrogol 15 Hydroxystearate (Solutol HS 15).\n\n          9. Female subject who is pregnant or lactating\n\n         10. Second malignancy unless in remission for >5 years. (Non-melanoma skin cancer or\n             carcinoma in situ of the cervix treated with curative intent is not exclusionary.)\n\n         11. Medical conditions that would impose excessive patient risk. Examples: uncontrolled\n             diabetes, infection requiring parenteral anti infective treatment, liver failure,\n             altered mental status or psychiatric condition that would interfere with the\n             understanding of the informed consent.\n\n         12. Unwilling or unable to comply with protocol.

Prior therapy with an anti-CSF1R antibody

GCTs: no limit of prior therapy

For Phase 2 only, have had disease progression or be refractory or intolerant to 1 prior line of therapy (first line therapy) for recurrent or refractory for NSCLC or HCC and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease. This may include multiple chemotherapeutic, targeted or immunotherapeutic agents with or without radiation therapy and/or surgery. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within the same drug class (eg, cisplatinum to carboplatinum) within a regimen in order to manage toxicity does not define the start of a new line of therapy.

Prior therapy - prior trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1) are allowed; patients who have received prior therapy with taselisib (GDC-0032) or BYL-719 are excluded; there is no limit on the number of prior lines of therapy

Subjects has failed or intolerant to temozolomide therapy.

Part B: More than 6 cycles of prior therapy with carboplatin

The last dose of prior systemic therapy (e.g. chemotherapy, targeted therapy etc) or radiation therapy (with the exception of palliative radiotherapy) was received less than 14 days prior to the first day of treatment

At least 1 prior line of therapy

No prior chemotherapy, radiation therapy, or surgery for this malignancy will be allowed; prior endoscopic procedures for superficial disease (endoscopic mucosal resection, cryotherapy, photodynamic therapy, etc.) will not exclude a patient; prior dilatation is also allowed

Any prior therapy for castrate disease is acceptable except prior specific cytochrome P450 family 17 (CYP17) antagonists (e.g. abiraterone acetate, orteronel) or prior second generation AR antagonists (e.g. enzalutamide or ARN509) which are excluded; a minimum washout of 28 days for any other anticancer therapy (with the exception of sipuleucel-T, which does not need a wash out) prior to first dose of study drug is required

hormonal therapy

Participants who have had prior anti-EGF or anti-HER2 therapy or cancer-directed chemotherapy

Treatment with any of the following therapies: \r\n* Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib hydrochloride OR\r\n* Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib\r\n* Patients who require chronic use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers including but not limited to grapefruit juice

Corticosteroid therapy and endocrine replacement therapy (L-thyroxine, testosterone, estrogen, desmopressin acetate [DDAVP]) are permissible; any patient already receiving human growth replacement therapy should discontinue this prior to commencing chemotherapy, and should not restart until 3 years from diagnosis

Biologic therapy

3. Receipt of any investigational anti-cancer therapy within 4 weeks prior to first dose of TAB001;

Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of DHES0815A

No intervening anti-cancer therapy between the last course of nivolumab or pembrolizumab and the first dose of study treatment is allowed except for local measures (e.g., surgical excision or biopsy, focal radiation therapy).

Asymptomatic untreated brain metastases are allowed; symptomatic metastases that have undergone local therapy with radiation therapy (RT) or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed; disease that has undergone local therapy is not considered measurable (for treatment phase)

Receipt of any other systemic anticancer therapy with the exception of hormonal therapy for a hormonally sensitive (e.g. breast or prostate) cancer (for treatment phase)

No prior systemic therapy for clear cell renal cancer

Treatment with any of the following anti-cancer therapies =< 14 days prior to registration:\r\n* Radiation therapy\r\n* Surgery or tumor embolization\r\n* Chemotherapy, immunotherapy\r\n* Biologic therapy\r\n* Investigational therapy\r\n* Hormonal therapy

Progression on at least one prior systemic therapy or progression during an observation phase of no anti-cancer therapy within the prior 3 months; prior taxanes are allowed

Have progressed on prior systemic therapy

Is expected to require any other form of anti-cancer therapy while in the trial. Zoledronic acid or denosumab as supportive care for bone metastases will be allowed if started prior to study enrollment

Use of protocol-defined prior/concomitant therapy.

Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy

Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior hormonal therapy: \r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy (including prior fulvestrant) in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment

Cohort A Dose Expansion (Ribociclib + PDR001): Prior hormonal therapy: \r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment

Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.

Prior medical therapy is allowed but not required

Escalation Phase: Subjects may be enrolled with ? 2 lines of prior systemic anti-cancer therapy (but no immunotherapy). Subjects who have had no prior systemic anti-cancer therapy (i.e. first-line therapy) or declined first-line treatment are permitted in the Escalation Phase.

Expansion Phase: Initially, only immunotherapy naïve subjects who have progressed on first-line cytotoxic chemotherapy or who have declined first-line treatment with cytotoxic chemotherapy will be enrolled. Subjects with no prior systemic anti cancer therapy (i.e. first line therapy) may be enrolled in a second cohort if approved by the SMC. Subjects previously treated with systemic adjuvant therapy, other than immunotherapy for recurrent advanced NSCLC, are also eligible.

Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy]; immune therapy, or cytokine therapy, except for erythropoietin.

Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy, with the following exception:\r\n* Any prior investigational anti-cancer therapy and/or monoclonal antibody is not permitted within 4 weeks of C1D1

Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 4 weeks prior to the initiation of study drug.

Inclusion criteria:\n\n        Dose escalation (Part 1A and Part 1B)\n\n          -  Patients with histologically confirmed, advanced unresectable or metastatic solid\n             tumor whom in the opinion of the Investigator does not have a suitable alternative\n             therapy.\n\n        Dose expansion (Part 2A)\n\n          -  Patients with histologically confirmed, advanced unresectable or metastatic melanoma\n             whom in the opinion of the Investigator does not have a suitable alternative therapy.\n\n          -  Patients must have failed a prior therapy based on anti-PD-1 or anti-PD-L1 as defined\n             by disease progression confirmed radiologically within 12 weeks of commencing\n             treatment without any evidence of a response.\n\n          -  Patients must have a site of disease amenable to biopsy and be a candidate for tumor\n             biopsy. Patients must be able to provide mandatory tumor biopsies prior to and during\n             study treatment.\n\n        Dose expansion (Part 2B)\n\n          -  Patients with histologically confirmed advanced unresectable or metastatic melanoma\n             who have failed a prior therapy based on anti-PD-1 or anti-PD-L1 or patients with a\n             specific type of colorectal adenocarcinoma who have progressed after last line of\n             therapy and have no other alternative approved standard therapy or refuse approved\n             standard therapy.\n\n        All cohorts\n\n          -  At least 1 measurable lesion by RECIST v1.1.\n\n          -  Patient understands and has signed Informed Consent form and is willing and able to\n             comply with the requirements of the trial.\n\n        Exclusion criteria:\n\n          -  Age <18 years.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status >1.\n\n          -  Concurrent treatment with any other anticancer therapy (including radiotherapy or\n             investigational agents) or participation in another clinical study.\n\n          -  Washout period of less than 3 weeks to prior anticancer therapy.\n\n          -  Women of reproductive potential and male subjects with female partners of childbearing\n             potential who are not willing to avoid pregnancy by using effective contraceptive.\n\n          -  Pregnant or breast-feeding women.\n\n          -  Unwillingness and inability to comply with scheduled visits, drug administration plan,\n             laboratory tests, other study procedures, and study restrictions.\n\n          -  Significant and uncontrolled concomitant illness, including any psychiatric condition.\n\n          -  Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic\n             therapy within 1 week prior to enrollment.\n\n          -  Any prior organ transplant including allogeneic bone marrow transplant.\n\n          -  History within the last 5 years of an invasive malignancy other than the one treated\n             in this study.\n\n          -  History of known human immunodeficiency virus (HIV), unresolved viral hepatitis.\n\n          -  Any major surgery within the last 28 days.\n\n          -  Patients with primary central nervous system (CNS) tumors and/or metastases.\n\n          -  History of severe, acute or chronic heart diseases.\n\n          -  History of severe, acute or chronic renal diseases or inadequate renal function.\n\n          -  Any of the following within 6 months prior to study enrollment: pulmonary embolism,\n             infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or\n             perforation and gastrointestinal hemorrhage.\n\n          -  Inadequate hematological or liver function.\n\n          -  Non-resolution of any prior treatment related toxicity to Grade <2.\n\n          -  Prior treatment with any anti-transforming growth factor ? (anti-TGF?) inhibitors.\n\n          -  Known allergies to any component of SAR439459 and/or REGN2810.\n\n          -  Patients who received prior immunotherapy who developed toxicity leading to a\n             permanent discontinuation of immunotherapy.\n\n          -  Ongoing or recent (within 2 years) evidence of significant autoimmune disease that\n             required treatment with systemic immunosuppressive treatments.\n\n          -  Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within\n             4 weeks prior to the first dose of SAR439459 and/or REGN2810 (occasional use of\n             inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).\n\n          -  History of pneumonitis or bowel perforation.\n\n          -  Patients with underlying cancer predisposition syndromes.\n\n        The above information is not intended to contain all considerations relevant to a patient's\n        potential participation in a clinical trial.

Treatment with any anti-cancer agent 14 days prior to Cycle, Day 1 other than aPD-1 based therapy

For Cohort C only: any prior anti-cancer therapy for advanced melanoma

relapsed and refractory multiple myeloma (RRMM): subjects who have received at least 2 prior regimen, were responsive to at least 1 prior regimen (as defined by IMWG criteria) and then are refractory to their most recent therapy (? 25% response or progression during therapy or within 60 days after completion of therapy). Prior therapies for subjects with PRMM or RRMM must include an immunomodulatory drug (IMiD) and a proteasome inhibitor as separate lines or a combined line of therapy. If prior therapy includes autologous stem cell transplantation (ASCT), then induction/ASCT/maintenance therapies will be considered as one line of therapy altogether. Subjects who have relapsed after ASCT or are unable to receive ASCT are eligible. The interval from ASCT to entry in the study must be ?12 weeks.

Immune therapy (including monoclonal antibody therapy) -6 weeks

Known intolerance to steroid therapy

For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.

Patient’s current disease state must be one for which there is not known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Prior neoadjuvant chemotherapy, endocrine therapy, or biologic therapy for current breast cancer [Period 2]

Prior immunotherapy is allowed.

Received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (or have not yet recovered from any actual toxicities of the most recent therapy) prior to the first scheduled dose of MM-310

Prior biologic therapy:\r\n* Patients must have discontinued all biologic or investigational therapy at least 21 days before registration

Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy. Prior therapy with weekly paclitaxel for recurrent disease, unless administered more than 2 years prior to enrollment, unless part of an upfront treatment strategy.

All hematologic, gastrointestinal, and genitourinary chemotherapy toxicities must be less than Grade 2 at the time study therapy is to begin. (Note: Transfusions may be used to correct hemoglobin for patients experiencing anemia from therapy who otherwise would be eligible for the study.

Use of any investigational agent. Use and/or receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal anti-bodies) within 14 days prior to the first dose of study therapy.

INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Actively on first line therapy for metastatic pancreatic cancer

INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients may be actively on “maintenance” therapy, such as maintenance capecitabine up to starting first line therapy for metastatic disease

Phase 1b only: Advanced solid malignancy with an emphasis on colorectal, head and neck, breast, pancreatic and ovarian cancers who have been treated with at least one regimen of prior systemic therapy, or who refuse systemic therapy, and for which there is no curative therapy available.

Major surgery, radiation therapy, or systemic anti-cancer therapy within 28 days of starting study treatment.

Participants who have received prior systemic therapy (chemotherapy or targeted therapy) within 7 days of Study Day 1 or those who have not recovered from clinically significant adverse events due to agents administered more than 7 days earlier. (continuation of the same regimen of HER-2 antibody targeted therapy agents, hormonal therapy and treatment with bisphosphonates or denosumab are permitted)

Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks

Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy)

Recent systemic anti-cancer therapy

COHORT A: Patients with newly diagnosed, previously untreated primary tumors that present with brain metastases should not forego available therapy that has demonstrated a definitive overall survival benefit as first line therapy for metastatic disease; therefore, in cases of previously untreated systemic solid tumors only those patients for whom there is no available therapy with definitive overall survival benefit, those that have failed at least one line of prior therapy for their primary tumor, or those refusing standard therapy will be eligible for this study; specifically, for patients with previously untreated primary tumors, the following diagnoses will be excluded: HER2-positive breast cancer; small cell lung cancer; non-small cell lung carcinoma (NSCLC) with targetable genomic tumor aberrations (e.g. EGFR, ALK)

No prior other anti-cancer therapy, including ACT, for 28 days prior to study administration of atezolizumab

Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Prior exposure to enzalutamide, ARN-509, or other investigational androgen receptor (AR)-directed therapy

Completion of other cancer therapy (targeted therapy, chemotherapy, investigational therapy, immunotherapy, radiotherapy, surgery) 14 days prior to first dose of protocol therapy\r\n* For patients with breast cancer only:\r\n** May continue ongoing antiestrogen therapy (for example, aromatase inhibitor)\r\n** May continue ongoing human epidermal growth factor receptor (Her)2 directed therapy (for example, trastuzumab)

Biopsy-proven advanced stage follicular lymphoma, that have failed at least two lines of therapy multi-agent chemotherapy, but responds to salvage therapy (i.e., chemosensitive disease) (timeline 8 months prior to enrollment)

Participants with hepatitis B should be on appropriate anti-viral therapy at the time of the transplant, and their viral load should be negative; timeline: within 3 weeks prior to enrollment

Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment

Prior cytoreductive therapy.

Inclusion Criteria:\n\n        To be eligible for participation in the study, patients must meet all of the following\n        inclusion criteria:\n\n          1. Patients enrolled in the Phase 1a study must:\n\n               1. Have a histologically confirmed diagnosis of advanced metastatic or progressive\n                  solid tumor\n\n               2. Be refractory to, or intolerant of, established therapy known to provide clinical\n                  benefit for their condition\n\n          2. Patients enrolled in the Phase 1b study must meet criteria for one of the following\n             tumor types:\n\n               1. Have tumors that have progressed despite immunotherapy and are felt to be\n                  appropriate for this type of treatment*\n\n               2. Have EGFR+ NSCLC and have progressed on ?2 lines of oral TKIs and are felt to be\n                  appropriate for this type of treatment*\n\n                  *Patients with immunotherapy-resistant tumors or EGFR+ NSCLC who are enrolled in\n                  these expansion cohorts will continue treatment with their previous immunotherapy\n                  or TKI regimens, respectively, and add TP-0903. The rationale is based on\n                  preclinical data that has shown that the combination is superior in patients who\n                  have progressed on prior immunotherapy or a TKI.\n\n               3. Have BRAF-, KRAS-, or NRAS-mutated CRC for whom there is no standard therapy\n                  remaining\n\n               4. Have persistent/recurrent ovarian cancer who would be platinum refractory/\n                  resistant and have had any number of lines of prior therapy\n\n               5. Have BRAF-mutated melanoma that has not responded to immunotherapy or a\n                  combination BRAF/MEK inhibitor\n\n          3. Have one or more tumors measurable or evaluable as outlined by modified RECIST v1.1\n\n          4. Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO])\n             performance of ?1\n\n          5. Have a life expectancy ?3 months\n\n          6. Be ?18 years of age\n\n          7. Have a negative pregnancy test (if female of childbearing potential)\n\n          8. Have acceptable liver function:\n\n               1. Bilirubin ?1.5x upper limit of normal (ULN)\n\n                  *Patients receiving immunotherapy should have a bilirubin level <3.0x ULN.\n\n               2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and\n                  alkaline phosphatase ?2.5x upper limit of normal (ULN)\n\n                    -  If liver metastases are present, then ?5x ULN is allowed.\n\n                    -  Patients receiving immunotherapy should have AST and ALT levels <5.0x ULN.\n\n          9. Have acceptable renal function:\n\n             a. Calculated creatinine clearance ?30 mL/min\n\n         10. Have acceptable hematologic status:\n\n               1. Granulocyte ?1500 cells/mm3\n\n               2. Platelet count ?100,000 (plt/mm3)\n\n               3. Hemoglobin ?9 g/dL\n\n         11. Have no clinically significant abnormalities on urinalysis\n\n         12. Have acceptable coagulation status:\n\n               1. Prothrombin time (PT) within 1.5x normal limits\n\n               2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits\n\n         13. Be nonfertile or agree to use an adequate method of contraception. Sexually active\n             patients and their partners must use an effective method of contraception (hormonal or\n             barrier method of birth control; or abstinence) prior to study entry and for the\n             duration of study participation and for at least 30 days after the last study drug\n             dose (see Section 4.6.3). Should a woman become pregnant or suspect she is pregnant\n             while participating in this study, she should inform her treating physician\n             immediately.\n\n         14. Have read and signed the IRB-approved informed consent form prior to any study related\n             procedure. (In the event that the patient is re-screened for study participation or a\n             protocol amendment alters the care of an ongoing patient, a new informed consent form\n             must be signed.)\n\n         15. Patients enrolled in each of the five Expansion Cohorts must be willing to consider\n             pre-study and on-study biopsies, if safe and medically feasible, as determined by\n             local interventional radiology (3 to 5 core samples requested at each biopsy\n             timepoint)\n\n        Patients meeting any one of these exclusion criteria will be prohibited from participating\n        in this study:\n\n          1. Have New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial\n             infarction within the past 6 months prior to Day 1, unstable arrhythmia, or evidence\n             of ischemia on electrocardiogram (ECG) or during Cardiac Stress Testing within 14 days\n             prior to Day 1 (Appendix C)\n\n          2. Have a corrected QT interval (QTcF, Fridericia's method) of >450 msec in men and 470\n             msec in women\n\n          3. Have a seizure disorders requiring anticonvulsant therapy\n\n          4. Presence of symptomatic central nervous system metastatic disease or disease that\n             requires local therapy such as radiotherapy, surgery, or increasing dose of steroids\n             within the prior 2 weeks\n\n          5. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting\n             O2 saturation of ?88% breathing room air)\n\n          6. Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior to\n             Day 1\n\n          7. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic\n             therapy\n\n          8. Are pregnant or nursing\n\n          9. Received treatment with radiation therapy, surgery, chemotherapy, or investigational\n             therapy within 28 days or 5 half lives, whichever occurs first, prior to study entry\n             (6 weeks for nitrosoureas or Mitomycin C)\n\n             a. This exclusion criterion is not applicable for patients with EGFR+ NSCLC or\n             immunotherapy-resistant tumors who are enrolled in expansion cohorts at the MTD.\n\n         10. Are unwilling or unable to comply with procedures required in this protocol\n\n         11. Have known infection with human immunodeficiency virus (HIV), hepatitis B, or\n             hepatitis C. Patients with history of chronic hepatitis that is currently not active\n             are eligible\n\n         12. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other\n             conditions) that could compromise protocol objectives in the opinion of the\n             investigator and/or the sponsor\n\n         13. Are currently receiving any other investigational agent\n\n         14. Have exhibited allergic reactions to a similar structural compound, biological agent,\n             or formulation\n\n         15. Have undergone significant surgery to the gastrointestinal tract that could impair\n             absorption or that could result in short bowel syndrome with diarrhea due to\n             malabsorption\n\n         16. Have a history of severe adverse reaction (eg, hypersensitivity reaction, anaphylaxis)\n             to sulfonamides

Is expected to require any other form of antineoplastic therapy while on study.

Previous treatment with any anti-CD30 directed therapy

Receipt of anti-cancer therapy 14 days prior to Cycle 1 Day 1

Patients who progressed after initial therapy\r\n* Subjects whose therapy changed due to suboptimal response, intolerance, etc., remain eligible, provided they do not meet criteria for progression\r\n* No more than two regimens will be allowed excluding dexamethasone alone

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib, other agents being investigated in combination with regorafenib)

Prior therapy with abemaciclib

CRC - No more than four different prior lines of systemic therapy for advanced disease

Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable)

Inclusion Criteria (Part 2 Only):\n\n          -  Histological or cytological diagnosis of locally advanced or metastatic NSCLC or\n             urothelial carcinoma who have progressed on or were intolerant to standard of care\n             systemic therapy, or for whom standard of care systemic therapy was refused (refusal\n             must be documented) or unavailable.\n\n          -  No prior treatment with anti-PD-1 or anti-PD-L1 therapy.\n\n          -  NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have\n             progressed on or after no more than 1 prior line of platinum-containing systemic\n             therapy or were intolerant or refused standard of care systemic therapy.\n\n          -  NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received\n             prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting\n             drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must\n             have progressed on or after both types of therapies.\n\n          -  Urothelial carcinoma patients must have received up to 2 lines of prior systemic\n             therapy and progressed on or after, experienced disease recurrence within 12 months of\n             neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused\n             platinum-containing systemic therapy.\n\n          -  Provide archived tumor tissue sample taken within the past 2 years or provide a fresh\n             tumor biopsy sample.\n\n          -  At least one measurable lesion as defined by RECIST version 1.1.\n\n          -  Adequate renal, liver, thyroid and bone marrow function.\n\n          -  Performance status 0 or 1.\n\n          -  Patient is capable of receiving study treatment for at least 8 weeks.\n\n        Exclusion Criteria (Part 2 Only)\n\n          -  Active brain or leptomeningeal metastases.\n\n          -  Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes\n             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone\n             replacement, psoriasis not requiring systemic treatment, or conditions not expected to\n             recur in the absence of an external trigger are permitted to enroll. Diagnosis of\n             prior immunodeficiency or organ transplant requiring immunosuppressive therapy or\n             prior allogeneic bone marrow or hematopoietic stem cell transplant.\n\n          -  Patients with a condition requiring systemic treatment with either corticosteroids\n             (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14\n             days of study drug administration. Inhaled or topical steroids, and adrenal\n             replacement doses >10 mg daily prednisone equivalents are permitted in the absence of\n             active autoimmune disease.\n\n          -  Patients with a history of interstitial lung disease, non-infectious pneumonitis, or\n             active pulmonary tuberculosis. Those with active lung infections requiring treatment\n             are also excluded.\n\n          -  History of Grade ?3 immune mediated AE (including AST/ALT elevations that where\n             considered drug related and cytokine release syndrome) that was considered related to\n             prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory\n             agents, etc.) and required immunosuppressive therapy.\n\n          -  Active hepatitis B or C, HIV/AIDS.\n\n          -  Other potentially metastatic malignancy within past 5 years.

Inclusion Criteria:\n\n          1. Male and female subjects at least 18 years at the time of screening\n\n          2. Adequate organ function within 14 days of enrollment confirmed by laboratory results\n\n          3. Off immunosuppressive medications including, but not limited to, systemic\n             corticosteroids at doses exceeding 10 mg/day prednisone or equivalent\n\n        Additional Inclusion Criteria for Part 1:\n\n          1. Metastatic/locally advanced solid tumor malignancy that has progressed on, is\n             refractory to, or for which there is no standard of care therapy\n\n          2. At least one lesion that is easily accessible for injection (subjects enrolled prior\n             to Amendment 3 only)\n\n          3. At least one deep-seated lesion suitable for intervention (subjects enrolled in the\n             deep-seated lesion expansion portion only)\n\n          4. At least 2 lesions (for subjects enrolled to evaluate addition of concurrent\n             palliative radiation to MEDI9197 therapy)\n\n        Additional Inclusion Criteria for Subjects in Part 2\n\n          1. Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological\n             findings consistent with CTCL\n\n          2. Stage IB, IIA or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with\n             measurable lesions\n\n          3. Previous treatment with at least one standard therapy used to treat the stage of\n             disease at study entry\n\n          4. At least 2 lesions amenable to response assessment\n\n        Additional Inclusion Criteria for Subjects in Part 3A and 3B\n\n        1. Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory\n        to, or for which there is no standard of care therapy\n\n        Exclusion Criteria:\n\n        Any of the following would exclude the subject from participation in the study:\n\n          1. Subjects who have received prior immunotherapy are NOT permitted to enroll unless all\n             of the following apply:\n\n               1. Prior anti-CTLA 4 inhibitor last dose administered at least 100 days ago. Other\n                  prior immunotherapies, the last dose administered at least 28 days prior to\n                  planned first dose of MEDI9197\n\n               2. Must not have experienced a toxicity that led to permanent discontinuation of\n                  prior immunotherapy\n\n               3. All AEs while receiving prior immunotherapy must have resolved to ? Grade 1 or\n                  baseline prior to screening for this study. Must not have experienced a ? Grade 3\n                  AE or neurologic, pneumonitis or ocular AE of any grade while receiving prior\n                  immunotherapy\n\n               4. Must not have required the use of additional immunosuppression other than\n                  corticosteroids for the management of an AE, not have experienced recurrence of\n                  an AE if re-challenged, and not currently require maintenance doses of > 10 mg\n                  prednisone or equivalent per day\n\n          2. Pregnant or lactating\n\n          3. Active bacterial, fungal, or viral infections\n\n          4. Active autoimmune disease, chronic inflammatory condition, conditions requiring\n             concurrent use of any systemic immunosuppressants or steroids\n\n          5. Immune-deficiency states - myelodysplastic disorders, marrow failures, human\n             immunodeficiency virus (HIV) infection, history of solid organ transplant or bone\n             marrow allograft, or recent pregnancy\n\n          6. Requires continuous anticoagulation or antiplatelet therapy.\n\n          7. History of coagulopathy resulting in uncontrolled bleeding.\n\n          8. Rapidly progressing disease\n\n          9. Untreated or uncontrolled central nervous system (CNS) involvement.\n\n         10. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer\n             treatment\n\n         11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to\n             NCI CTCAE v4.03 Grade 0 or 1, with exception of alopecia, vitiligo and laboratory\n             values listed per inclusion criteria\n\n         12. Chronic active hepatitis B or C\n\n         13. Known allergy to sesame oil and/or nuts\n\n         14. Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure,\n             uncontrolled hypertension, unstable angina pectoris, clinical important cardiac\n             arrhythmia, mean QTC interval corrected for heart rate >500ms\n\n         15. Major surgery within 4 weeks prior to study entry or still recovering from prior\n             surgery\n\n         16. Receipt of live, attenuated vaccine within 28 days prior to study entry.\n\n         17. Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks\n             or 5 half-lives\n\n         18. Subjects with CTCL, must not have had prior therapy with Imiquimod, total body\n             electron beam radiation, investigational drugs or treatments within 8 weeks. They must\n             not have had prior therapy with local radiation, UBV therapy, PUVA, any topical\n             chemotherapy, photopheresis, systemic retinoids, corticosteroids, immune response\n             modifiers, IFN inducers, chemotherapeutic agents or biological agents or any topical\n             treatment within 4 weeks. They must not have a known history or positive test for\n             infection with HTLV-1.\n\n         19. Cognitive disorder such that informed consent cannot be obtained directly from the\n             subject\n\n         20. Subjects who have previously participated in this study and received MEDI9197.\n\n         21. Subjects who have received prior TLR agonists, both systemic and topical.\n\n         22. Patients who have received prior therapeutic radiation within 28 days of dosing. All\n             toxicities from prior radiotherapy must have resolved to ? Grade 1 or baseline prior\n             to dosing.

Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, radiotherapy, or ablation; provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy

Patients treated with first generation anti-androgen as most recent systemic therapy (bicalutamide, nilutamide) must have at least 4 weeks elapsed from treatment discontinuation to start of protocol therapy with evidence of disease progression by Prostate Cancer Working Group 2 (PCWG2) criteria following discontinuation of prior anti-androgen

Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects must have received conventional therapy as a prior therapy.

Has received the prohibited therapy (e.g., concurrent anti-cancer therapy including but not limited to: chemotherapy, radiation, hormonal, or immunotherapy) ?14 days prior to first planned dose of AC0010MA.

Concurrent or planned systemic chemotherapy, radiotherapy, new hormonal or anti- HER2 directed therapy directed at management of breast cancer (existing anti-HER2 therapy can be continued as recently recommended in the National Consensus Guidelines)

Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.

ARM 2: Must have had at least 1 but no more than 3 prior lines of anti-myeloma therapy; may be refractory to lenalidomide but sensitive to carfilzomib; prior exposure to carfilzomib is allowed but may not be refractory to carfilzomib; subjects must be >= 8 weeks from last carfilzomib therapy

A line of therapy is defined as a course of therapy that is not interrupted by progressive disease; for example, induction therapy, autologous stem cell transplantation, and maintenance therapy without intervening progressive disease is one line of therapy

Prior radioisotope therapy

Anti-platelet therapy, except low-dose aspirin for cardioprotection

Radiation therapy, chemotherapy, immunotherapy, investigational therapy or corticosteroid use within 2 weeks of or after eligibility-defining bone marrow biopsy. Bisphosphonates and denosumab are permitted if subject has been receiving for at least 90 days

Prior systemic therapy for incurable disease

Any prior therapy targeted against PSMA

Prior therapy: Patients must have discontinued all chemotherapy, investigational therapy or biologic therapy at least 14 days prior to initiating study treatment (with the exception of trastuzumab for patients with HER2+ breast cancer)

Patients on bisphosphonates may continue receiving bisphosphonate therapy during study; patients wanting to initiate bisphosphonate therapy may do so

Patients must not have received prior systemic therapy for PTCL (except for corticosteroids for 10 or fewer days at any dose, no washout period required as long as they discontinue prior to starting study therapy); NOTE: topical treatment may have been given for prior existence of cutaneous lymphoma that has since become systemic PTCL; however, these topical therapies should be stopped at time of registration

For patients whose most recent anti-DLBCL therapy induced a PR or CR, at least 60 days must have elapsed since the end of that therapy. For all other patients, at least 14 weeks must have elapsed since their most recent systemic anti-DLBCL therapy.

Must have relapsed or refractory disease after 2 or more prior lines of therapy; 1 line of therapy is allowed, if it included an autologous stem cell transplant and at least 12 weeks have elapsed from day 0; a line of therapy is defined as a course of therapy that is not interrupted by progressive disease

Part 1: A confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ? 1 prior therapy for FL, or subjects who have not previously received systemic anticancer therapy for FL., and which requires treatment. Part 2:Histologically confirmed MZL including splenic, nodal, and extranodal sub- types

Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF mutation-negative and has received >1 prior systemic therapy for metastatic melanoma

Expected to require any other form of systemic or localized antineoplastic therapy while in this study

Inclusion Criteria:\n\n        For Advanced GI Malignancies (Dose Escalation and MTD Cohorts):\n\n          1. Advanced histologically proven GI cancer.\n\n          2. First line or progressive disease if already treated with any form of therapy,\n             including but not limited to chemotherapy, radiotherapy, local therapy, surgery or\n             immuno-therapy. Patients with HCC who failed sorafenib, with documented PD or AEs that\n             resulted in discontinuance of that agent. Patients with pancreatic cancer (dose\n             escalation only) who have progressed following a gemcitabine based regimen. Subjects\n             failing prior platinum containing regimens are eligible. Gastric cancer subjects that\n             express tumor HER-2 amplification must be treated with trastuzumab prior to\n             enrollment, unless trastuzumab is not available for those indications in a particular\n             country.\n\n          3. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable\n             lesion must be present. Subjects who have received local-regional therapy such as (but\n             not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy,\n             percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery\n             are eligible, provided that they have either a target lesion which has not been\n             treated with local therapy and/or the target lesion(s) within the field of the local\n             regional therapy has shown an increase of ? 20% in size. Local-regional therapy must\n             be completed at least 4 weeks prior to the baseline CT scan.\n\n          4. ECOG performance status of 0 - 1.\n\n          5. Expected survival of at least 3 months.\n\n        For HCC (Dose Escalation and MTD Expansion):\n\n        19. Prior treatment with sorafenib, with documented PD or AEs that resulted in\n        discontinuance of that agent. Patient may have been treated with other lines off therapy as\n        well excluding ADI-PEG 20.\n\n        20. Cirrhotic status of Child-Pugh grade A. Child-Pugh status should be determined based on\n        clinical findings and laboratory data during the screening period (Appendix C). Subjects on\n        Coumadin anti-coagulants are to receive only 1 point for their INR status.\n\n        21. Serum albumin level ? 2.8 g/dl. 22. Prothrombin time (PT)-international normalized\n        ratio (INR): PT <6 seconds above control or INR <1.7. Subjects on Coumadin anti-coagulants\n        are to receive only 1 point for their INR status.\n\n        23. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such\n        treatment, except for interferon.\n\n        Exclusion Criteria:\n\n          1. Serious infection requiring treatment with systemically administered antibiotics at\n             the time of study entrance, or an infection requiring systemic antibiotic therapy\n             within 7 days prior to the first dose of study treatment.\n\n          2. Pregnancy or lactation.\n\n          3. Expected non-compliance.\n\n          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure (New York Heart Association Class III\n             or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit\n             compliance with study requirements.\n\n          5. Subjects who have had any anticancer treatment prior to entering the study and have\n             not recovered to baseline (except alopecia) or ? Grade 1 AEs, or deemed irreversible\n             from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a\n             safety risk by the Sponsor and investigator may be allowed upon agreement with both.

For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.

For Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.

For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.

For Part D (LY2835219 + exemestane): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with exemestane.

Treatment with systemic steroids for > 4 weeks prior to cycle 1 day 1 of study therapy; prior radiation therapy, with the exception of an abbreviated course (not more than 3 days) if used for superior vena cava (SVC) syndrome

Patients who have had immunotherapy, chemotherapy or radiotherapy within 14 days prior to the first dose of navitoclax, or prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to first dose of dabrafenib and/or trametinib; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment; biologics will not be allowed within 30 days prior to, or during, navitoclax administration

Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, topical therapy such as 5-fluorouracil or imiquimod, radiation therapy, surgery, or photodynamic therapy\r\n* For patients with multiple cutaneous BCCs at baseline that are not designated by the investigator as target lesions, treatment of these non-target BCCs with surgery may be permitted but must be discussed with data coordinator prior to any surgical procedure

For patients with LABC, no prior therapy is allowed

LVEF < 50% during previous trastuzumab therapy

Prior treatment of this cancer including:\r\n* Surgery\r\n* Radiation therapy\r\n* Chemotherapy\r\n* Biotherapy\r\n* Hormonal therapy \r\n* Investigational agent prior to study entry

Recovery from effects of recent surgery, radiotherapy, or chemotherapy\r\n* Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted\r\n* Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration; if the prior therapy was with bevacizumab then at least 4 weeks after treatment discontinuation must have elapsed prior to treatment on this study

All subjects must have failed 1+ prior treatment, one of which must include lenalidomide therapy\r\n* Patients requiring second (2nd) line of therapy must meet criteria of lenalidomide-refractory disease defined as a history of progression on or within 60 days of completion of a regimen of a minimum of 2 cycles containing full or maximally tolerated dose of lenalidomide\r\n** Patients progressing on lenalidomide maintenance in the first line of therapy will be eligible provided that they have received at least 2 cycles of lenalidomide at established standard maintenance dosing schedule; maintenance dosing and schedule must be documented and approved by lead principal investigator prior to enrollment \r\n* For patients requiring third (3rd) or higher line of therapy, history of treatment with lenalidomide is required but lenalidomide-refractory status is not\r\n* In addition, subjects also refractory to pomalidomide, carfilzomib, or bortezomib are permitted limited to 10 subjects per group

Subject has received anti-cancer chemotherapy, immunotherapy, hormonal (with the exception of hormones for thyroid conditions or estrogen replacement therapy [ERT], or any investigational therapy) within 21 days of enrollment

Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biological agent

At least 3 weeks from prior systemic treatments including investigational anti-cancer therapy, radiation therapy; and have recovered from prior toxicities

Subjects on bisphosphonate therapy must be on a stable dose and must have started therapy > 4 weeks prior to protocol therapy.

Subjects must have completed systemic therapy at least 28 days prior to first dose.

Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.

Prior systemic therapy:\r\n* Participants must have discontinued systemic therapy at least 14 days prior to initiating protocol therapy.\r\n* There is no limit to the number of prior lines of systemic therapy. Participants who have not received any systemic therapy for metastatic disease are also eligible.\r\n* Participants may initiate or continue bisphosphonate therapy on study

Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy

Chemotherapy or targeted therapy within 14 days prior to cycle 1 day 1 of protocol therapy

No washout is required for endocrine therapy; if a patient has been on endocrine therapy within 28 days of study entry, that same endocrine therapy is permitted to be continued during protocol therapy, at the investigator’s discretion, as is continuation of ovarian suppression in premenopausal women; starting a new endocrine therapy during protocol therapy is not permitted

If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy.

Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study entry.

Previously treated with an anti-DKK1 therapy

Glucocorticoid therapy allowed.

Subjects must not have had prior RT, chemotherapy (including Gliadel wafer), immunotherapy or therapy with a biologic agent, or hormonal therapy.

Is expected to require any non-protocol antineoplastic therapy while on study.

Ongoing or planned systemic anti-cancer therapy or radiation therapy

Participant has received anti-cancer traditional medicine or anti-cancer herbal remedies within 14 days prior to ABBV-744 dosing. Saw palmetto is considered anti-cancer herbal remedy. Participant with CRPC who has received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within a period of 21 days prior to Study Day 1. Participant with AML has received anti-cancer therapy within a period of 14 days or 5 half-lives (whichever is longer; except for immunotherapy where a period of 21 days will be acceptable) prior to Study Day 1. Except for hydroxyurea which will be allowed during screening and treatment for controlling leukocytosis for AML subjects.

Subjects must have recovered from all toxicity associated with previous chemotherapy, targeted therapy, experimental therapy, biological therapy, immuno-oncology therapy, surgery, radiotherapy, or other locoregional therapy. (Exception: Subjects may enter with continuing alopecia.) The following intervals must elapse between end of last treatment and receiving the first dose of SM08502:

Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Major surgery within 28 days of starting study treatment; -or- systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment -or- recent radiation therapy with unresolved toxicity.

Not a candidate for potentially curative therapy at the time of enrollment

Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.

Patients must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma if standard treatment is appropriate. Treatment naive patients may be enrolled if they have refused standard systemic treatment. Prior adjuvant therapy will not count provided it was completed more than 6 months previously.

Treatment including radiation therapy, chemotherapy, or targeted therapy, for the currently diagnosed breast cancer prior to randomization.

Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks prior to initiation of study treatment

Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ?3 weeks before the start of study therapy.

Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational; prior therapy with bisphosphonates is allowed; prior radiation therapy to a solitary plasmacytoma is allowed

A) Patients enrolled into the dedifferentiated liposarcoma cohort do not require prior systemic therapy (may be naive to systemic therapy); B) leiomyosarcoma patients must have had at least 1 prior systemic therapy (does not include adjuvant/neoadjuvant therapy in a curative setting). There are no limits on prior number of therapies for either cohort

Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment

Prior treatment of PTCL with systemic anti-lymphoma therapies, investigational agents, radiation; exception: may have received 1 cycle of CHOP-like therapy (e.g. CHOP, CHOEP, EPOCH); these participants must initiate day 1 cycle 1 of CHEP-BV no less than 19 days from prior CHOP-like therapy

Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy

Concomitant anticancer therapy, systemic immune therapy, or hormonal therapy as cancer therapy

No prior Y90 radioembolization for HCC is permitted; therapies below are allowed but must be completed 4 weeks prior to baseline scan:\r\n* Prior transarterial embolization (TAE) or transarterial chemoembolization (TACE)\r\n* One treatment of stereotactic body radiation therapy (SBRT)\r\n* Liver resection\r\n* Ablation therapy

Patients may continue therapy with a targeted agent if CNS disease developed while receiving the agent, and for defined regimens that have been deemed safe when combined with anti-PD-1 therapy

Patients who are candidates for local salvage therapy must have had this option pursued or discussed; and the patient must have either declined salvage therapy or was deemed not to be a candidate for salvage therapy

Prior radiation therapy to the liver including 90Y , I131 based loco regional therapy. Prior loco regional therapy, including resection, based on other technology for ICC, if any, must have been completed at least 4 weeks prior to baseline imaging.

Subjects on long term (>= 6 months) first generation anti-androgen therapy (e.g. flutamide, bicalutamide, nilutamide) will need to discontinue anti-androgen therapy for 4 weeks prior to registration (wash out period) and show evidence of disease progression off the anti-androgen; subjects that have been on a first generation anti-androgen 6 months or less will need to discontinue therapy prior to registration (no wash out period required)

Subjects on second generation anti-androgen therapy (enzalutamide) or androgen bio-synthesis inhibitor (abiraterone acetate) will need to discontinue therapy 2 weeks prior to registration (wash out period)

Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 4 weeks prior to the initiation of study drug administration.

Prior systemic therapy:\r\n* Participant must be at least 14 days from the last dose of prior chemotherapy, endocrine therapy, biological agents (including small molecule targeted therapy) or any investigational drug product with adequate recovery of toxicity to baseline, or grade 1 (with the exception of alopecia and hot flashes) at the time of registration\r\n* There is no limit to the number of prior lines of therapy, including endocrine or cytotoxic agents; systemic treatment naive patients for metastatic disease are also eligible\r\n* Participants may initiate or continue bisphosphonate therapy on study\r\n* Continuation of ovarian suppression is allowed

Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after all Food and Drug Administration (FDA)-approved therapy

Is expected to require any other form of antineoplastic therapy while on study.

One prior systemic therapy in the metastatic setting is allowed, but patients who have not had any prior systemic therapies in the metastatic setting are also eligible\r\n* Note: patients who were started on endocrine therapy monotherapy as their 1st line or 2nd line systemic therapy in the metastatic setting for no more than 28 days and without clinical progression prior to the initiation of the study drug therapy are allowed to enroll on the study as their 1st line or 2nd line therapy, respectively

Currently receiving exogenous estrogen replacement therapy (topical vaginal estrogen therapy is allowed)

Must have had at least two (2) prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)

Patients must be receiving optimal therapy for their extracranial disease according to local practice at each center. Patients may continue on systemic therapy while receiving TTFields.

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Limited prior therapy, including hydroxyurea for 72 hours or less, systemic glucocorticoids for one week or less, one dose of vincristine, and one dose of intrathecal chemotherapy

Patients with prior therapy, other than therapy specified above

Concurrent administration of any other anti-cancer therapy (except male participants with prostate cancer receiving androgen blockade: Bisphosphonates and denosumab are allowed; Most recent anti-cancer therapy </=28 days and have not recovered from the side effects, excluding alopecia; Radiaiton therapy within </=14 days

Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior to date of randomization and total duration of prior therapy is ? 36 months.

Prior therapy: No line limit but no more than 1 prior regimens in the platinum resistant setting; no prior treatment targeting the ATR/checkpoint kinase 1 (CHK1) pathway and no prior gemcitabine as single agent; hormonal therapies immunotherapy, and antiangiogenic therapies (as single agents) do not count as lines; poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP)-inhibitors count as a line of therapy unless given in the maintenance setting; PARP-inhibitors given as maintenance after platinum therapy do not count as a line of therapy; prior carboplatin/gemcitabine is allowed provided that there was no disease progression within 12 months after completion of the carboplatin/gemcitabine regimen; subjects may begin protocol treatment at least 4 weeks or 5 half-lives, whichever is shorter, after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible

ALK+ ALCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen including an anthracycline, if not contraindicated, and prior brentuximab; prior crizotinib or other ALK inhibitor therapy, while recommended, is not mandatory; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant

Prior treatment:\r\n* Patients may have received prior radiation therapy to index lesions >= 28 days prior to registration on this protocol if there has been documented progression by RECIST criteria; prior radiation therapy to the non-index lesions is allowed if >= 28 days prior to registration on this protocol\r\n* Prior RAI therapy is allowed if >= 90 days prior to registration on this protocol and evidence of progression (as defined above) has been documented in the interim (a diagnostic study using < 10 mCi of RAI is not considered RAI therapy)\r\n* Prior chemotherapy is allowed if >= 28 days prior to registration on this protocol\r\n* Patient may have received any number of prior lines of therapy\r\n* No prior use of sorafenib or an mammalian target of rapamycin (mTOR) (including phosphoinositide 3-kinase [PI3k] or protein kinase B [AKT]) inhibitor for the treatment of thyroid cancer

Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.

Concurrent anticancer therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy)

Patients must be weaned off prednisone and be off therapy for >= 1 week prior to starting therapy

There is no limitation on the number of prior lines of systemic therapy

Note: HER2 mutation testing may be performed while the patient is receiving active systemic therapy for metastatic breast cancer so that the result can be used to determine eligibility for study drug therapy in the future

Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-? reductase inhibitor is permitted.

Inclusion Criteria (Preliminary Screening)\n\n          1. Signed Preliminary Screening Informed Consent Form obtained prior to any study\n             specific assessments and procedures\n\n          2. Age ?18 years (or per national guidelines)\n\n          3. Participants must have histologically confirmed invasive breast cancer that is\n             metastatic or not amenable for resection or radiation therapy with curative intent.\n             Histological documentation of metastatic/recurrent breast cancer is not required if\n             there is unequivocal evidence for recurrence of the breast cancer.\n\n          4. Patients must have histologically confirmed HER2+ and hormone receptor positive (ER+\n             and/or PR+), metastatic breast cancer. ER, PR and HER2 measurements should be\n             performed according to institutional guidelines, in a CLIA-approved setting in the US\n             or certified laboratories for Non-US regions. Cut-off values for positive/negative\n             staining should be in accordance with current ASCO/CAP (American Society of Clinical\n             Oncology/College of American Pathologists) guidelines.\n\n          5. Patients must agree to provide a representative formalin-fixed paraffin-embedded\n             (FFPE) tumor tissue block (preferred) from primary breast or metastatic site\n             (archival) OR at least 15 freshly cut unstained slides from such a block, along with a\n             pathology report documenting HER2 positivity and hormone receptor positivity.\n\n          6. Patients should be willing to provide a representative tumor specimen obtained from\n             metastatic disease if clinically feasible. This is a recommended but optional research\n             biopsy.\n\n             Inclusion Criteria (Randomization Screening)\n\n          7. Signed Main Informed Consent Form obtained prior to any study specific assessments and\n             procedures\n\n          8. Age ? 18 years (or per national guidelines)\n\n          9. ECOG performance status 0-1\n\n         10. Patients must be able and willing to swallow and retain oral medication without a\n             condition that would interfere with enteric absorption.\n\n         11. Serum or urine pregnancy test must be negative within 7 days of randomization in women\n             of childbearing potential. Pregnancy testing does not need to be pursued in patients\n             who are judged as postmenopausal before randomization, as determined by local\n             practice, or who have undergone bilateral oophorectomy, total hysterectomy, or\n             bilateral tubal ligation. Women of childbearing potential and male patients randomized\n             into the study must use adequate contraception for the duration of protocol treatment\n             and for 6 months after the last treatment with palbociclib if they are in Arm A and\n             for 7 months after last treatment with trastuzumab if in either Arm A or Arm B\n             Adequate contraception is defined as one highly effective form (i.e. abstinence,\n             (fe)male sterilization OR two effective forms (e.g. non-hormonal IUD and condom /\n             occlusive cap with spermicidal foam / gel / film / cream / suppository).\n\n         12. Resolution of all acute toxic effects of prior induction anti-HER2-based chemotherapy\n             regimen to NCI CTCAE version 4.0 Grade ?1 (except alopecia or other toxicities not\n             considered a safety risk for the patient at investigator's discretion) 12 weeks\n             between last dose of chemotherapy-anti-HER2therapy and randomization are allowed.\n             Endocrine therapy could start before study randomization.\n\n         13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory\n             tests, and other study procedures\n\n             Prior Treatment Specifics\n\n         14. Patients may or may not have received neo/adjuvant therapy, but must have a\n             disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis ?6\n             months.\n\n         15. Patients must have received an acceptable, standard, chemotherapy containing anti-HER2\n             based induction therapy for the treatment of metastatic breast cancer prior to study\n             enrollment. For this study, chemotherapy is limited to a taxane or vinorelbine (only\n             for trastuzumab-based regimen). Eligible patients are expected to have completed 6\n             cycles of chemotherapy containing anti-HER2-therapy treatment. A minimum of 4 cycles\n             of treatment is acceptable for patients experiencing significant toxicity associated\n             with treatment as long as they are without evidence of disease progression (i.e. CR,\n             PR or SD). The maximum number of cycles is 8. Patients can randomize immediately\n             following completion of their induction therapy, or for those who have already\n             completed induction, a gap of 12 weeks between their last infusion/dose of induction\n             therapy and the C1D1 visit is permitted. Patients are eligible provided they are\n             without evidence of disease progression by local assessment (i.e. CR, PR or SD).\n\n         16. Participants with a history of treated CNS metastases are eligible, provided they meet\n             all of the following criteria:\n\n               -  Disease outside the CNS is present.\n\n               -  No evidence of interim progression between the completion of CNS-directed therapy\n                  and the screening radiographic study\n\n               -  No history of intracranial hemorrhage or spinal cord hemorrhage\n\n               -  Not requiring anti-convulsants for symptomatic control\n\n               -  Minimum of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and\n                  recovery from significant (Grade ? 3) acute toxicity with no ongoing requirement\n                  for corticosteroid\n\n             Baseline Body Function Specifics\n\n         17. Absolute neutrophil count ? 1,000/mm3\n\n         18. Platelets ? 100,000/mm3\n\n         19. Hemoglobin ? 10g/dL\n\n         20. Total serum bilirubin ? ULN; or total bilirubin ? 3.0 × ULN with direct bilirubin\n             within normal range in patients with documented Gilbert's Syndrome.\n\n         21. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ?\n             3 × institutional ULN (?5 x ULN if liver metastases are present).\n\n         22. Serum creatinine within normal institutional limits or creatinine clearance ? 60\n             mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.\n\n         23. Left ventricular ejection fraction (LVEF) ? 50% at baseline as determined by either\n             ECHO or MUGA\n\n        Exclusion Criteria (Randomization)\n\n          1. Concurrent therapy with other Investigational Products.\n\n          2. Prior therapy with any CDK 4/6 inhibitor.\n\n          3. History of allergic reactions attributed to compounds of chemical or biologic\n             composition similar to palbociclib.\n\n          4. Patients receiving any medications or substances that are strong inhibitors or\n             inducers of CYP3A isoenzymes within 7 days of randomization (see Section 8.6.3 for\n             list of strong inhibitors or inducers of CYP3A isoenzymes).\n\n          5. Uncontrolled current illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac\n             arrhythmia, diabetes, or psychiatric illness/social situations that would limit\n             compliance with study requirements. Ability to comply with study requirements is to be\n             assessed by each investigator at the time of screening for study participation.\n\n          6. Pregnant women, or women of childbearing potential without a negative pregnancy test\n             (serum or urine) within 7 days prior to randomization, irrespective of the method of\n             contraception used, are excluded from this study because the effect of palbociclib on\n             a developing fetus is unknown. Breastfeeding must be discontinued prior to study\n             entry.\n\n          7. Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are\n             ineligible because of the potential for pharmacokinetic interactions or increased\n             immunosuppression with palbociclib.\n\n          8. QTc interval >480 msec, Brugada syndrome or known history of QTc prolongation or\n             Torsade de Pointes.\n\n          9. Patients with clinically significant history of liver disease, including viral or\n             other known hepatitis, current alcohol abuse, or cirrhosis

No prior chemotherapy, biologic therapy, hormonal therapy or investigational therapy for this operable breast cancer

Inclusion Criteria:\n\n        Part A:\n\n          -  Subjects must have signed written informed consent.\n\n          -  Male or female subjects age greater than equals to (>=)18 years.\n\n          -  Subjects must have histologically or cytologically proven metastatic or locally\n             advanced solid tumors for which no standard therapy exists, standard therapy has\n             failed, subject is intolerant of established therapy known to provide clinical benefit\n             for their condition, or standard therapy is not acceptable to the subject.\n\n          -  Subjects who have been treated previously with a checkpoint inhibitor may enroll\n             (except as outlined below for expansion cohorts).\n\n          -  At least 1 unidimensional radiographically measurable lesion based on Response\n             Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), except for subjects\n             with metastatic castration-resistant prostate cancer (CRPC) or metastatic breast\n             cancer who may be enrolled with objective evidence of disease without a measureable\n             lesion.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at Screening\n\n          -  Estimated life expectancy of more than 12 weeks\n\n          -  Adequate hematological function as defined below:\n\n               -  White blood cells (WBC) count >= 3.0 × 10^9 per liter (/L)\n\n               -  Absolute neutrophil count >= 1.5 × 10^9/L\n\n               -  Lymphocyte count >= 0.5 × 10^9/L\n\n               -  Platelet count >= 100 × 10^9/L\n\n               -  Hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)\n\n          -  Adequate hepatic function as defined below:\n\n               -  A total bilirubin level lass than equals to (<=) 1.5 × the upper limit of normal\n                  (ULN) range • Aspartate aminotransferase (AST) levels <= 2.5 × ULN (? 3 × ULN for\n                  expansion cohorts)\n\n               -  Alanine aminotransferase (ALT) levels <= 2.5 × ULN (? 3 × ULN for expansion\n                  cohorts)\n\n               -  Subjects with documented Gilbert disease are allowed if total bilirubin > 1.5 but\n                  less than 3 × ULN\n\n          -  Adequate renal function as defined by an estimated creatinine clearance >= 50\n             milliliter per minute (mL/min) according to the Cockcroft-Gault formula\n\n          -  Negative blood pregnancy test at Screening for women of childbearing potential. For\n             the purposes of this trial, women of childbearing potential are defined as all female\n             subjects after puberty unless they are postmenopausal for at least 1 year, are\n             surgically sterile or are sexually inactive.\n\n          -  Highly effective contraception (ie, methods with a failure rate of less than 1% per\n             year) must be used before the start of treatment, for the duration of the trial\n             treatment, and for at least 50 days after stopping study treatment for both men and\n             women if the risk of conception exists. The effects of avelumab and NHS-IL12 on the\n             developing human fetus are unknown; thus, women of childbearing potential and men must\n             agree to use highly effective contraception.\n\n        Part B:\n\n          -  Urothelial carcinoma (UC) post-platinum: Histologically or cytologically confirmed\n             locally advanced or metastatic transitional cell carcinoma of the urothelium\n             (including renal pelvis, ureters, urinary bladder, and urethra). Subjects must have\n             progressed after treatment with at least 1 platinum containing regimen for inoperable\n             locally advanced or metastatic UC or disease recurrence. Availability of either tumor\n             archival material (< 6 months old)or fresh biopsies (obtained within 28 days) is\n             acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded\n             samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor\n             archival material must be suitable for biomarker assessment.\n\n          -  Non-small cell lung cancer (NSCLC), first-line metastatic: Stage IV (per seventh\n             International Association for the Study of Lung Cancer classification) histologically\n             confirmed NSCLC. Subjects must not have received treatment for their metastatic\n             disease. Subjects could have received adjuvant chemotherapy or loco-regional treatment\n             that included chemotherapy for locally advanced disease, as long as disease recurrence\n             occurred at least 6 months after the completion of the last administration of\n             chemotherapy. Only epidermal growth factor receptor (EGFR) and anaplastic lymphoma\n             kinase (ALK) wild-type are allowed (ie, EGFR mutation and ALK translocation / re\n             arrangement excluded). Non squamous cell histologies and never / former light smoker\n             (< 15 pack years) squamous cell carcinoma subjects (per local standard of care)\n             require testing if status is unknown. Subjects must have low tumor PD-L1 expression\n             defined as < 50% tumor proportion score determined using PD-L1 IHC 22C3 pharmDx test\n             or an equivalent Food and Drug Administration (FDA)- approved PD-L1 test. Availability\n             of either tumor archival material or fresh biopsies within 28 days is acceptable with\n             one of these being mandatory. For FFPE samples, either block or sections (> 15) may be\n             provided. Tumor biopsies and tumor archival material must be suitable for biomarker\n             assessment. This cohort will not be opened for enrollment in Belgium, Czech Republic,\n             Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom.\n\n          -  Colorectal cancer (CRC): Histologically or cytologically confirmed recurrent or\n             refractory metastatic CRC (according to American Joint Committee on Cancer /\n             International Union Against Cancer Tumor Node Metastasis [TNM] Staging System seventh\n             edition) after failure of prior therapy containing oxaliplatin / fluoropyrimidine and\n             / or irinotecan / fluoropyrimidine and, if eligible, cetuximab (Erbitux®) and\n             bevacizumab (Avastin®). Only subjects with microsatellite instability (MSI)-low or\n             microsatellite stable (MSS) metastatic CRC are eligible. Subjects without existing MSI\n             test results will have MSI status performed locally by a Clinical Laboratory\n             Improvement Amendments (CLIA)-certified IHC or polymerase chain reaction (PCR)-based\n             test (PCR based MSI test is preferred). Subjects must be willing to undergo an\n             on-treatment biopsy procedure. Availability of either tumor archival material or fresh\n             biopsies within 28 days is acceptable with one of these being mandatory. For FFPE\n             samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor\n             archival material must be suitable for biomarker assessment. For Belgium, Czech\n             Republic, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom, subjects in\n             the second-line setting should have exhausted or be considered ineligible or\n             intolerant (in the opinion of the Investigator) of available second-line chemotherapy\n             options.\n\n          -  Renal cell carcinoma (RCC), primary immune checkpoint inhibitor failure:\n             Histologically or cytologically documented metastatic RCC with a component of clear\n             cell subtype. Subjects must have had progressive disease (PD) within 6 months or best\n             overall response of stable disease (SD) for ? 6 months following start of therapy with\n             any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such\n             as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) for\n             advanced or metastatic disease (either as monotherapy or combination therapy, in any\n             line). Availability of a fresh tumor biopsy is mandatory for eligibility in the RCC\n             cohort. The biopsy or surgical specimen should be collected within 28 days prior to\n             the first IMP administration. Subjects must also be willing to undergo an on-treatment\n             biopsy procedure.\n\n        Exclusion Criteria:\n\n          -  Concurrent treatment with a non-permitted drug/intervention (listed below)\n\n               -  Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy,\n                  cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any\n                  investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior\n                  to start of trial treatment, or not recovered from adverse event (AE) related to\n                  such therapies, with the following exceptions: Palliative radiotherapy delivered\n                  in a normal organ-sparing technique is permitted; Erythropoietin and\n                  darbepoetin-? are permitted; Hormonal therapies acting on the\n                  hypothalamic-pituitary-gonadal axis are permitted (i.e. luteinizing\n                  hormone-releasing hormone agonist/antagonists). No other hormonal anticancer\n                  therapy is permitted.\n\n               -  Major surgery (as deemed by Investigator) for any reason, except diagnostic\n                  biopsy, within 4 weeks prior to start of trial treatment, or not fully recovered\n                  from surgery within 4 weeks prior to start of trial treatment\n\n               -  Subjects receiving immunosuppressive agents (such as steroids) for any reason\n                  should be tapered off these drugs before start of trial treatment, with the\n                  following exceptions: Subjects with adrenal insufficiency, may continue\n                  corticosteroids at physiologic replacement dose, equivalent to ? 10 mg prednisone\n                  daily; Administration of steroids through a route known to result in a minimal\n                  systemic exposure (topical, intranasal, intra-ocular, or inhalation) is\n                  permitted; Previous or ongoing administration of systemic steroids for the\n                  management of an acute allergic phenomenon is acceptable as long as it is\n                  anticipated that the administration of steroids will be completed in 14 days, or\n                  that the dose after 14 days will be equivalent to <= 10 mg prednisone daily.\n\n          -  Any prior treatment with any form of interlukin-12 (IL-12)\n\n          -  For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug\n             targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1,\n             anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody is prohibited.\n\n          -  Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE\n             requiring drug discontinuation.\n\n          -  Active or history of primary or metastatic central nervous system tumors\n\n          -  Prior organ transplantation, including allogeneic stem-cell transplantation\n\n          -  Previous malignant disease (other than the indication for this trial) within the last\n             5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of\n             skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission\n             without further recurrence was achieved at least 2 years prior to trial entry and the\n             subject was deemed to have been cured with no additional therapy required or\n             anticipated to be required.\n\n          -  Significant acute or chronic infections requiring systemic therapy including, among\n             others:\n\n               -  History of testing positive test for human immunodeficiency virus (HIV) or known\n                  acquired immunodeficiency syndrome\n\n               -  Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody\n                  positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core\n                  antibody positive alone with reflex to positive HBV DNA or positive hepatitis C\n                  virus [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]).\n                  Subjects with history of infection must have polymerase chain reaction\n                  documentation that infection is cleared.\n\n          -  Active or history of autoimmune disease that might deteriorate when receiving an\n             immuno-stimulatory agent. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or\n             hyperthyroid disease not requiring immunosuppressive treatment are eligible if they\n             are stable on other medical treatment and do not fulfill exclusion criterion including\n             Uncontrolled intercurrent illness\n\n          -  Known severe hypersensitivity reactions to monoclonal antibodies (Grade>= 3 National\n             Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or\n             uncontrolled asthma (ie, 3 or more features of partially controlled asthma)\n\n          -  History of allergic reaction to methotrexate (trace methotrexate may be present in\n             NHS-IL12 as a part of the manufacturing process) or history of severe hypersensitivity\n             reaction to any other ingredient of the study drug(s) and / or their excipients. Since\n             NHS-IL12 contains sucrose as an excipient, subjects suffering from hereditary fructose\n             intolerance are also excluded\n\n          -  Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v4.03 with the\n             following exceptions:\n\n               -  Neuropathy Grade <= 2 is acceptable.\n\n               -  All grades of alopecia are acceptable.\n\n               -  Endocrine dysfunction on replacement therapy is acceptable.\n\n          -  Pregnancy or lactation\n\n          -  Known alcohol or drug abuse as deemed by the Investigator\n\n          -  Uncontrolled intercurrent illness including, but not limited to:\n\n               -  Hypertension uncontrolled by standard therapies (not stabilized to 150/90\n                  millimeter of mercury (mm Hg) or lower)\n\n               -  Uncontrolled active infection\n\n               -  Uncontrolled diabetes (eg, glycosylated hemoglobin [HgbA1c] >= 8%)\n\n          -  Clinically significant (or active) cardiovascular disease: cerebral vascular\n             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months\n             prior to enrollment), unstable angina, congestive heart failure (New York He

Patients who are currently being treated with cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) other than the trial therapy.

Patients must have been treated with at least one prior systemic regimen for sarcoma; adjuvant systemic therapy qualifies as prior therapy for the purposes of this study; there is no upper limit on previous lines of therapy received; a prior line of systemic therapy may include prior investigational agents received as part of other clinical studies

Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy including hematopoietic stem cell transplantation.

Adult subjects with advanced MDS or CMML requiring therapy who were previously treated with either azacitidine or decitabine for at least 4 cycles and deemed to have failed therapy due to progression of disease using International Working Group (IWG) criteria (“refractory”) or losing their previously documented response to the therapy (“relapsed”) and who are ineligible for allogeneic stem cell transplant

Patients who are actively receiving any other anticancer therapy except for hormonal therapy for well-controlled breast or prostate cancer

Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational; prior therapy with bisphosphonate is allowed; prior radiation therapy to a solitary plasmacytoma is allowed

More than one prior line of systemic therapy for advanced CRC

Having gotten prior PD1 therapy is allowed for, especially if they have previously progressed on it; progression may include extra-cranial as well as intra-cranial progression; after progressing on PD1 therapy, intervening chemotherapy and/or targeted therapy (BRAF inhibitors [BRAFi], etc) is allowed; if they are on intervening chemotherapy and/or targeted therapy (BRAFi, etc), they have to have progression intra-cranially and/or extra-cranially and must be off intervening therapy for at least 2 weeks

Participants who have had prior local regional therapy including radiation therapy, transarterial therapy, or ablative therapy

Receiving glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy alone for cGVHD at study entry. Subjects on calcineurin therapy only, without glucocorticoid therapy, are not eligible. Subjects also receiving other therapies thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), will be considered for enrollment in this study on a case-by-case basis.

For patients who have received prior radiation, cryotherapy, radiofrequency ablation, TheraSphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* 28 days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measureable

Prior infusion of a genetically modified therapy

Is expected to require any other form of antineoplastic therapy while on study.

The patient has received 1 to 3 prior lines of therapy; by definition, a single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy; radiotherapy, bisphosphonate, or a single short course of steroids (i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy

Have received prior gene therapy or therapy with cytolytic virus of any type

Other form(s) of antineoplastic therapy anticipated during the period of the study.

?28 days for prior systemic corticosteroid therapy.

At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL and ineligible for (or failed) autologous or allogeneic stem cell transplant (SCT) (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment). NOTE: For follicular lymphoma transformed to DLBCL (t-FL/DLBCL), single agent non-cytotoxic therapy will not be considered as a line of therapy.

Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) or any other systemic anticancer therapy within 2 weeks of study entry.

1 to 4 prior lines of therapy

concomitant anti-cancer therapy (other then BTZ/Dex and bisphosphonates

Patients who received any of the following within the 14 days before initiating study treatment: major surgery, radiation therapy, and/or systemic therapy (standard or an investigational or biological anticancer agent).

Need for treatment with any conventional modality for prostate cancer (surgery, radiation therapy, and hormonal therapy)

No more than two prior lines of cytotoxic-containing chemotherapy regimens for advanced disease. There is no limit for prior targeted therapy, hormonal therapy and immunotherapy (such as nivolumab).

Treatment with any anticancer therapy

Prior chemotherapy, prior epidermal growth factor receptor (EGFR) targeted therapy, or prior radiation therapy for HNSCC

EXPANSION COHORT: No more than one line of prior systemic therapy for advanced pancreatic adenocarcinoma allowed

Status post 1 or more unmatched systemic therapy regimens for enrollment to group 3

Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives of day 1

Prior therapy with any systemic therapy (chemotherapy or biologic therapy) within twenty-eight days prior to study entry

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib, other agents being investigated in combination with regorafenib)

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment; the washout period between radiation therapy or tumor embolization is two weeks; given the refractory nature of the study population, the washout period between study treatment and prior chemotherapy or biological therapy, will be three weeks prior to use of regorafenib

no effective conventional therapy exists

Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the exceptions stated in the protocol

Prior CAR therapy within 30 days prior to apheresis or prior CAR therapy at any time with evidence for persistence of CAR T cells in blood samples (circulating levels of genetically modified cells of >= 5% by flow cytometry)

Relapse or progression after at least 1 systemic therapy

Prior systemic therapy

Previous and concomitant therapy that precludes enrollment, as defined in the protocol

All patients must have had at least one appropriate first line systemic therapy and progressed

Prior therapy with afatinib

A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for < 3 months require only a 2 week washout period prior to first dose of study drug

Currently receiving progestin therapy (local, topical, or systemic)

Patients may have had no more than 3 prior lines of systemic therapy; prior therapy with a MET inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent

Patients receiving other treatment for breast cancer (includes standard hormonal therapy, chemotherapy, biologic therapy, immunotherapy, or radiation therapy). Patients receiving chronic bisphosphonate or denosumab therapy are eligible.

Prior anti-androgen therapy

Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy (Note: extracorporeal photopheresis will be considered a systemic therapy for this study)

Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 14 days should have elapsed from the last day of radiation; NOTE: prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator

Phase II: histologically confirmed colorectal adenocarcinoma post at least two lines of therapy, NSCLC post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy; patients must have measurable disease

Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), or any systemic corticosteroid, must discontinue the agent for at least four weeks prior to ipilimumab treatment; progressive disease as defined above must be documented after discontinuation of any hormonal therapy (with the exception of a LHRH agonist)

Prior treatment with an anti-CTLA-4 antibody treatment; the course of sipuleucel-T therapy (i.e. three treatments) leading up to this investigational trial must be the first course of therapy these patients have received

Use of systemic corticosteroid therapy within 2 weeks of study enrollment, including patients receiving replacement corticosteroid therapy; note: only topical, inhaled and intranasal steroid therapy is permitted

There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy

Emergent radiation therapy, one dose of intrathecal chemotherapy, and up to 7 days of steroids for treatment of relapse are permitted before start of treatment in participants who relapse after completion of frontline therapy

Patients may not be receiving any other investigational agents during protocol therapy, or up to 30 days prior to beginning protocol therapy; there should be a least a 1-week interval between last dose of endocrine therapy and protocol therapy, and at least 3 weeks for the last dose of biologic therapy (eg, bevacizumab) or cytotoxic therapy (or 2 weeks for capecitabine or weekly paclitaxel, 6 weeks for mitomycin-C and nitrosoureas), and adequately recovered from adverse effects from prior therapy to meet all other eligibility criteria

Subjects currently on anti-coagulation therapy are not eligible

If they are undergoing or have undergone in the past 4 weeks (28 days) any other therapy for their cancer, including radiation therapy and adjuvant therapy

Patients receiving full dose anticoagulative therapy

Has received chemotherapy, immunotherapy, biologic therapy or endocrine therapy within the past 12 weeks

A minimum of 4 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation; in addition, recovery to grade 1 or less from all reversible toxicities related to prior therapy is required at study entry

No more than two prior regimens targeting the VEGF pathway; no prior bevacizumab therapy

No prior purine analog therapy except up to 1 prior course of either cladribine or pentostatin

No prior hormonal therapy for lung cancer

=< 14 days before first dose of protocol-indicated treatment:\r\n* Anti-cancer therapy with an approved or investigational agent (including chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or biological therapy).\r\n* Radiosurgery or radiotherapy. (Note: A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion.)\r\n* Initiation of a new erythropoietin, darbepoietin, and/or bisphosphonate therapy.\r\n* Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery.)\r\n* Serious or uncontrolled infection.\r\n* Infection requiring parenteral antibiotics. (Note: Patients with a non-serious infection under active treatment and controlled with oral antibiotics initiated at least 10 days prior to initiation of protocol-indicated treatment are not excluded – e.g. urinary tract infection controlled with oral antibiotics.)\r\n* Unexplained fever > 38.0 degree Celsius (C).

No concurrent anticancer therapy. Required washout from prior therapy:\r\n* Endocrine therapy: no required wash-out\r\n* Chemotherapy: 14 days\r\n* Major surgery: 14 days (provided wound healing is adequate)\r\n* Radiation: 7 days\r\n* Investigational/biologic therapy (half-life =< 40 hours): 14 days\r\n* Investigational/biologic therapy (half-life > 40 hours): 28 days.

Prior therapy:\r\n* Patients may have received unlimited prior treatment for the dose escalation part\r\n* For the expansion cohort patients must have ? 4 prior lines of chemotherapy\r\n* Hormonal therapy does not count towards total lines of therapy\r\n* Maintenance therapy is considered part of the preceding regimen if one or more of the same drugs are continued\r\n* Neoadjuvant and adjuvant chemotherapy are considered one regimen if they are a continuation of the same regimen with interval debulking surgery

No prior therapy for rectal cancer.

Prior malignancies requiring systemic therapy within the last 3 years (as prior therapy can increase toxicity of current chemo regimen, those patients should be excluded).

Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol.

No prior therapy to primary tumor prior to surgical resection (no induction therapy or recurrent disease).

Anticancer treatment within 14 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative radiotherapy delivered in a normal organ-sparing technique], immune therapy, or cytokine therapy).

Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting, and including a platinum containing regimen)

Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible 1 week after treatment as long as the target lesion is not the treated lesion

ALL patients refractory to liposomal vincristine as defined by progression while on therapy or relapse within 3 months of completion of therapy with liposomal vincristine

Prior immuno-oncology therapy

At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids

Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0 as well as current participation or recipient of treatment on a clinical trial within 28 days prior to Day 0;

Any prior anticancer therapy for esophageal cancer

Must receive optimal therapy for extracranial disease and may continue on systemic therapy during TTF administration

Financial coverage for proton therapy

One to four prior lines of therapy

Prior therapy with at least one first-line standard of care treatment or second-line treatment of proven effectiveness; patients must have progressive disease after prior treatment; prior first-line or second-line treatments would include the following:\r\n* Patients with metastatic melanoma: receipt of a checkpoint inhibitor as first-line therapy\r\n* Patients with metastatic melanoma with an activating mutation of KIT: receipt of imatinib\r\n* Patients with a BRAF V600 activating mutation: receipt of appropriate targeted therapy\r\n* Patients with metastatic gastrointestinal cancer: receipt of up to two forms of approved first- and/or second-line chemotherapy regimens\r\n* Patients with metastatic genitourinary cancers: receipt of a first- or second-line therapy appropriate for their histologic subtype

Any prior therapy with daratumumab

Prior therapy with etoposide and cyclophosphamide is allowed

Any subject who is a candidate for intensive induction therapy and agrees to receive this therapy

Previous intrapleural therapy for MPE on the same side

Greater than 2 lines of prior systemic therapy for CRPC

Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior to tumor resection for preparing TIL therapy.

No prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL with the exception of palliative loco-regional radiotherapy and corticosteroids for symptom control

IO therapy resistant or insensitive tumors

Patients must be either refractory to or relapsed after 1 line of therapy

Received investigational therapy (e.g. small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval. Acceptable washout periods include:

Prior therapy with LMB-100

Anticancer treatment within 14 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative radiotherapy delivered in a normal organ-sparing technique], immune therapy, or cytokine therapy).

Patients requiring anti-coagulant therapy

Prior cognitive-behavioral therapy

Prior therapy, including everolimus, octreotide, surgery, chemoradiation, is all permitted after being properly noted; this prior therapy must have been completed at least 28 days prior to study enrollment

MCL has been previously treated and has relapsed after or progressed during prior therapy.

Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ?1 week before the start of study therapy.

Prior anti-ROR1 therapy within 12 weeks prior to the start of study therapy.

Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma; an exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., chondrosarcoma); any patient that refuses standard chemotherapy for the treatment of their disease is also considered eligible; prior adjuvant therapy will not count provided it was completed more than 6 months previously

Use of any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other than GnRH agonists within 28 days of the start of treatment on protocol. Use of bone targeted agents including bisphosphonates and RANK ligand inhibitors is allowed if on stable dose; Xgeva or Zometa cannot be started within 28 days of initiating study therapy.

Systemic steroid therapy required, except for patients with glioblastoma (cohort 4)

Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy\r\n* Note: extracorporeal photopheresis will be considered a systemic therapy for this study

Prior therapy with lenalidomide

Has had any systemic anti-cancer therapy (includes anti-VEGF therapy or any systemic investigational anti-cancer agent)

Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy

Patients currently on cytotoxic chemotherapy or immunotherapy are eligible, not including anti-VEGF therapy

GENERAL: Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.

Prior anti-cancer therapy as specified below: At least 28 days from enrollment must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc). Note: Patients who experienced immune -related pneumonitis, pituitary or thyroid dysfunction, or pancreatitis while on treatment with immune-oncology agents will be excluded; Other anti-cancer therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 14 days prior to enrollment; Radiation therapy completed within 14 days prior to enrollment; Prior CAR T therapy or other genetically modified T cell therapy.

Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to the initiation of study treatment. The following exceptions are allowed: hormone-replacement therapy or oral contraceptives

Prior systemic therapy for current diagnosis of HNSCC

Patients who have had chemotherapy, hormonal therapy (except LHRH agonist or antagonist), immunotherapy, radioisotope therapy, or RT within 21 days prior to start of the study agents

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Any anticancer therapy within 14 days prior to the first dose of study drug, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)

Naive to prior systemic anti-cancer therapy for melanoma

No prior therapy for this disease

Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., osteoporosis) is allowed

Prior CD19 directed therapy other than blinatumomab

Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry.

Prior exposure to immune-mediated therapy

There is no limitation of amount or the type of prior therapy or drugs

Last dose of anticancer therapy (including HER2-targeted therapy) within 14 days prior to randomization.

At least 1 line of androgen receptor (AR)-targeted therapy (for example {e.g

Arm A: MBC with progression and no prior endocrine based systemic therapy in the metastatic setting;

Antibody therapy

Prior, concomitant or planned treatment with Novo-TTF, EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy

Prior treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting. Patients must have progressed on or following, the most recent line of therapy.

No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed

(Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy

Received at least one line of therapy with sorafenib and/or regorafenib with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with sorafenib and/or regorafenib; no more than two lines of prior therapy are allowed

Prior treatment\r\n* With any prior anti-CD19/anti-CD19 CAR-T or cellular therapy (prior blinatumomab therapy is allowed)\r\n* Treatment with any prior gene therapy\r\n* Prior allogeneic hematopoietic stem cell transplant\r\n* Received chemotherapy, radiation or surgical resection of malignancy within 2 weeks prior to the start of lymphodepleting chemotherapy (day -10 to -5)

Current treatment with anti-viral therapy for HBV.

Patients must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation and/or biological therapy regimen for their recurrent and/or metastatic HNSCC; however, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy

Prior therapy with other HER2 targeted agents is not required, such as T-DM1 or pertuzumab

Patients refractory to prior therapy with trastuzumab are eligible

Chemotherapy, targeted small molecule therapy, radiotherapy, experimental agents, prior therapy with anti-tumor vaccines or other immune-stimulatory antitumor agents, or biological cancer therapy (including monoclonal antibodies) within 14 days prior to the start of study drug, or not recovered (=< grade 1 or baseline) from adverse events due to a previously administered agent

Have received any number of prior systemic therapies for metastatic disease; prior radiation therapy (any number) and interferon use (any formulation and/or duration) in the adjuvant or metastatic disease settings is permitted; vaccine therapy will be counted as systemic therapy

Expected to require any other form of systemic or localized antineoplastic therapy while on study

Expected to require any other form of systemic or localized anticancer therapy while on study.

Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.

Estimated creatinine clearance < 30 mL/min or use of renal replacement therapy (e.g., hemodialysis, continuous renal replacement therapy, peritoneal dialysis) within 7 days prior to Day 1

Participants must have had prior therapy

Patients must have had at least 4 prior lines of therapy

Patient may be enrolled at any time from last line of therapy

Patients must not have had chemotherapy, major surgery, monoclonal antibody therapy or experimental therapy within the 21 days prior to the start of ibrutinib administration

No prior genetically modified cell therapy that is still detectable or virotherapy allowed

Systemic therapy is allowed but SBRT cannot begin until >= 7 days after the last cycle of systemic therapy, and systemic therapy cannot be initiated or re-initiated until >= 7 days after SBRT; there will be no limit on prior lines of systemic therapy

Use of protocol-defined prior/concomitant therapy.

14 day wash-out period from any previous chemotherapy, targeted therapy or radiotherapy, 21 day washout period from previous immunotherapy

Hormone replacement therapy or vaginal estrogen therapy, DHEA, or biosynthetics within 6 weeks prior to enrollment

Receipt of anti-cancer therapy prior to Cycle 1 Day 1: no chemotherapy, radiation therapy, small molecule tyrosine kinase inhibitor (TKI), or hormonal therapy for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1. No immune therapy or other biologic therapy (other monoclonal antibodies or antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1 Day 1.

Any line of prior therapy allowed.

Use of bisphosphonate therapy for osteoporosis will be allowed if started prior to study enrollment

Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed

Subjects must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options are also eligible. a) Subjects with relapsed and/or refractory lymphoma must have had at least 2 prior lines of systemic therapy and are not candidates for high dose therapy/autologous stem cell transplant.

Adult patients stage IV lung cancer or melanoma receiving commercial supply immune checkpoint inhibitor therapy with progression of disease, and for whom an additional 4-6 weeks of current therapy (post-progression therapy) is acceptable as standard therapy

Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

Current treatment with chemotherapy or radiation therapy; any prior therapy directed at the malignant tumor, including biologic and immunologic agents, must be discontinued at least three weeks prior to registration

Prior therapy targeted to EGFRvIII

Patients may not be receiving the concomitant administration of any systemic therapy, biologic therapy, or other agents with anti-tumor activity against prostate cancer while the patients are on study.

Histological confirmation of advanced biliary tract cancers including cancers originating in gallbladder who have received at least one line of systemic anticancer therapy; \r\n* Note: Patients who have either progressed or intolerant to the prior therapy can be included in this study

Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks of enrollment

Prior use of an immunotherapy such as (but not limited to) a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy

Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 14 days of registration

Patients receiving any concomitant systemic therapy for renal cell cancer are excluded.

Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy

Patients who received prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiotherapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to day 1 of cycle 1. Patients are permitted to be on dabrafenib and trametinib at start of therapy without wash-out period prior to day 1 of cycle 1. Dosing will change to protocol determined dose levels on day 1 of cycle 1.

Patients must have had two or more lines of prior therapy (chemo or hormonal) in the metastatic setting

Has had prior chemotherapy, targeted small molecule therapy, monoclonal antibody therapy, or radiation therapy within 2 weeks prior to on-study date\r\n* Note: If currently receiving hormonal therapy or chemotherapy, this treatment must be stopped at least 2 weeks prior to on-study date; hormonal therapy may be restarted after the restaging scan 1 month after the 8th BATs infusion\r\n* Note: Radiation therapy to the axial skeleton must be completed at least 2 weeks prior to on-study date

Indication for initiation of therapy

Prior systemic cytotoxic therapy, antineoplastic biologic therapy, or major surgery within 28 days of first dose of study medication

Within 28 days before first dose of protocol-indicated treatment:\r\n* Anti-cancer treatment including chemotherapy, radiation, hormonal therapy, targeted therapy, immunotherapy, or biological therapy\r\n* Major surgery requiring general anesthesia; (Note: within this time frame, placement of a central line or portacath is acceptable and does not exclude)\r\n* Receipt of an investigational agent

Any other anticancer therapy (e.g., chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, radiation therapy, intravesical therapy, investigational agent) within 28 days of the first dose of study therapy (and within 6 weeks for nitrosourea or mitomycin C) other than a single dose of intravesical chemotherapy which is permitted between 28 days and 14 days prior to the first dose of study treatment

Relapsed/refractory disease, or inadequate response to at least 6 cycles of hypomethylating therapy. Subjects must not have received any MDS or MAL directed therapy for >28 days prior to receiving the study treatment.

Prior therapy with anti-CD137 or ISA101.

Subject is actively on anticoagulation therapy.

Biological (anti-neoplastic) therapy: ? 7 days prior to screening.

Any anti-cancer therapy including chemotherapy, hormonal therapy, or radiotherapy within 2 weeks prior to initiation of study treatment; or herbal therapy intended as anti-cancer therapy within 1 week prior to initiation of study treatment

Patients may not be receiving any other anti-cancer therapy.

Concurrent anticancer non protocol directed therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy)

No prior genetically modified cell therapy that is still detectable >= 5% in the peripheral blood

Prior cancer therapy (except for endocrine therapy) must have been discontinued for 1 week prior to initiation of study drugs

Received at least one prior line of cancer therapy for the treatment of NSCLC; this should include at least one of the following: platinum (carboplatin or cisplatin) doublet chemotherapy (acceptable combinations include: paclitaxel, docetaxel, abraxane, pemetrexed, gemcitabine, vinorelbine, or etoposide), anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab), or appropriate targeted therapy in patients with activating EGFR (osimertinib, erlotinib, gefitinib, or afatinib), ALK (alectinib, crizotinib, ceritinib, brigatinib, or loralatinib), or ROS-1 (crizotininb or entrectinib) alterations; therapy may be given as monotherapy or in combination with other cancer therapy (e.g. bevacizumab, ipilumimab)

Relapsed or refractory AML, who require salvage therapy

No prior MM-directed therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m^2) and/or cyclophosphamide up to 1000 mg/m^2 administered for management of acute manifestations of MM (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment. If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available

Patient can have had prior treatment for HCC including prior surgery, radiation therapy, local-regional therapy (abalation or arterial directed therapies), and systemic therapy including sorafenib or chemotherapy (but not anti-PD-1 or anti-CTLA-4 therapy)

More than 5 lines of prior systemic therapy in the preceding three years

131I therapy < 6 months prior to initiation of therapy on this protocol; a diagnostic study using < 10 mCi of 131I is not considered 131I therapy

Patients, who have previously received in vivo anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging, are eligible unless they have had an anaphylactic reaction attributed to anti-GD2 therapy

History of anaphylaxis attributed to prior anti-GD2 therapy

Patients who have had anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents), large field radiotherapy, or major surgery must wait 4 weeks after completing treatment prior to entering the study

Prior anti-tumoral radionuclide therapy with unsealed sources; prior therapy with sealed radioactive sources such as brachytherapy will be allowed

Patients may be on somatostatin analogue therapy (e.g. but not only limited to sandostatin or lanreotide therapy); however, therapy with somatostatin analogues should not be initiated or altered within 3 months of study enrollment; patients on short term octreotide may have dose held for 24 hours prior to Lu-177-DOTATATE therapy; those on long acting octreotide therapy will receive treatment at 1 to 5 days prior to their next cold octreotide dose, in order to prevent competition for the receptor

have received chemotherapy, hormonal therapy, biologic therapy, immunotherapy or radiation therapy within 14 days prior to the planned start of study treatment.

Patients must have had at least two, but not more than four prior lines of therapy for their disease, with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period

Prior treatment with more than 2 lines of therapy (combination treatments are considered 1 line of therapy)

Pregnant and nursing: female patients must have a negative serum pregnancy test within 72 hours prior to initiating protocol therapy and be practicing an effective form of contraception during protocol therapy and for at least 4 weeks following completion of protocol therapy

Must have progressed on at least one line of prior therapy for metastatic disease, or be intolerant to that therapy if they have not progressed, and for HER2+ disease should have received prior trastuzumab

Failure or intolerance to at least one prior therapy for the current disease

Receipt of systemic anticancer therapy, including investigational agents, within 28 days prior to study treatment (Note: If anticancer therapy was given within 28 days prior to starting study treatment, patients are not excluded if ? 5 times the elimination half-life of the drug has elapsed.)

Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate > 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.

At least one measurable intracranial target lesion for which all of the following criteria are met: a) Previously untreated or progressive after previous local therapy b) Immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy c) Largest diameter of >= 0.5 cm, but =< 3 cm as determined by contrast-enhanced MRI

Any approved anticancer therapy, including chemotherapy and hormonal therapy within 3 weeks prior to initiation of study treatment; however, the following are allowed: a) Hormone-replacement therapy or oral contraceptives b) Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)

Bisphosphonate therapy for symptomatic hypercalcemia a) Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Concomitant use of any anti-cancer therapy or radiation therapy

Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy

Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD.

Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy.

For estrogen receptor (ER)-positive breast cancer, patients must be considered refractory to endocrine therapy, having received and progressed through at least one prior line of endocrine therapy, or are intolerant of endocrine therapy

Any of the following for the treatment of cancer within 2 weeks of first study treatment: chemotherapy, immunotherapy, experimental therapy, or biologic therapy

Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy, including investigational agents for their disease

Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (hormone replacement therapy is acceptable), radiotherapy (except for palliative), biological therapy or other novel agent) or live virus and live bacterial vaccines while the patient is receiving study medication. Strong or moderate CYP3A inhibitors and inducers should not be taken with study treatment; however, if no other suitable alternative concomitant medication is available, dose reductions may be allowed under careful monitoring

Prior Therapy (for patients with R/R PTCL):\r\n* Exposure to any agent targeting PD-1, PD-L1 or CTLA-4\r\n* Previous therapy with any of the drugs contained in the regimen the patient is assigned to receive; in this case, the patient will be enrolled in the next treatment arm that does not contain such drugs, according to the sequence Arm A -> Arm B -> Arm C ->Arm D\r\n* Exposure to biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation therapy within 2 weeks prior to entering the study or lack of resolution of adverse events (AE) due to previously administered antineoplastic therapy to grade 1 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0\r\n* Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab; the following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10mg/day of prednisone or equivalent for at least 5 days prior to the start of the study drugs\r\n* Prior allogeneic SCT

Prior treatment with any CD19-directed therapy (e.g. blinatumomab, CD19-directed chimeric antigen receptor T-cell therapy, anti-CD19 antibodies)

Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug

Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day 1.

Allowed prior therapy:\r\n* Newly diagnosed DLBCL and low grade B cell lymphoma: No prior therapy is allowed except steroids equivalent to maximum of prednisone 20 mg once daily for maximum of seven days prior to registration\r\n* Relapsed/refractory low grade B cell lymphoma (only allowed in phase I): A minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line\r\n* For patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of RCHOP-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks

Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy

Patients who are actively receiving any other anticancer therapy

Prior therapy with single-agent gemcitabine.

Patients should not have received any systemic therapy (including chemotherapy, biologic therapy or immunotherapy) =< 7 days prior to treatment

Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed:\r\n* Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging\r\n* Hormone-replacement therapy or oral contraceptives

Has received therapy for this current diagnosis of breast cancer including endocrine therapy or chemotherapy

Patients must not have had leukemia therapy for 14 days prior to starting palbociclib. However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study

Prior biologic therapy: Patients must have discontinued all biologic therapy at least 21 days before registration

Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting; prior cytokine therapy (eg, IL-2, IFN-alpha), vaccine therapy, or treatment with cytotoxics is also allowed

Male who has a pregnant partner, and is not willing to use a condom during sexual activity while receiving protocol-specified therapy and for 3 months after the last dose of protocol-specified therapy.

Prior therapy:\r\n* Any number of prior chemotherapy regimens and/or targeted therapies and/or prior external beam radiation therapy and/or prior hormonal therapy for endometrial cancer are allowed provided the last treatment was > 4 weeks prior to registration\r\n* Vaginal brachytherapy may have been administered at any time prior to registration

No prior therapy, or limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy (e.g., to the mediastinum, head and neck, orbit, etc.) and one dose of intrathecal chemotherapy

Receipt of the last dose of anti-cancer therapy (cytotoxic chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug (28 days prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors [TKIs] [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C [if sufficient wash-out time has not occurred due to the schedule or pharmacokinetic [PK] properties of an agent, a longer wash-out period may be required])

Prior therapy with oxaliplatin

Patients with plans to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) or other systemic therapy (including chemotherapy, target therapy and other type of immunotherapy or investigative agents) while on this protocol, except at disease progression, are not eligible

Patients who have received previous investigational agents or biologic therapy, such as tipifarnib, pirfenidone, Peg-Intron, sorafenib, imatinib or other targeted therapies are eligible for enrollment; at least 4 weeks must have elapsed since receiving medical therapy directed at the plexiform neurofibromas (PN) and patients who received previous GIST-directed therapy must either demonstrate progression as defined by RECIST, or be unable to tolerate their previous therapy; patients who received prior medical therapy for their PN must have recovered from the acute toxic effects of all prior therapy to =< grade 1 before entering this study

Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at the tumor; those patients with a plexiform neurofibroma requiring treatment will be eligible

Prior systemic therapy for advanced RCC; however, treatment with immunotherapy (i.e., high-dose bolus IL-2, ipilimumab + nivolumab, etc.) is allowed

CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION

Documentation of CD19 expression on any prior or current tumor biopsy; patients who have received previous CD19-targeted therapy must have CD19-positive disease confirmed on a biopsy since completing the prior CD19-targeted therapy

Inclusion Criteria\n\n        Part A Dose Escalation: Patients must have histological or cytological confirmation of a\n        solid tumour known to harbour KRAS mutations (e.g., NSCLC, mCRC, pancreatic or\n        cholangiocarcinoma), and have progressed despite standard therapy(ies), or are intolerant\n        to standard therapy(ies), or have a tumour for which no standard therapy(ies) exists.\n\n        Part B Expansion: Patients in Part B must have measurable disease as measured by Response\n        Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1\n\n        Group 1. Patients must have histological or cytological confirmation of locally advanced or\n        metastatic KRASm+ NSCLC, who have failed prior therapy and for whom no current therapy is\n        available.\n\n        Group 2. Patients must have histological or cytological confirmation of locally advanced or\n        metastatic KRASm+ NSCLC, who have failed prior therapy and for whom no current therapy is\n        available. At study entry patients must be clinically suitable for mandatory baseline and\n        on-treatment tumour biopsies.\n\n          1. Signed written informed consent\n\n          2. ? 18 years old\n\n          3. All patients must have KRAS mutations identified in tumour tissue samples from a prior\n             test conducted by a clinical laboratory that has received international or country\n             specific certification. Mutations may include but are not limited to:\n\n             NSCLC KRAS mutations in codons G12/13, Q61, and A59\n\n             mCRC KRAS mutations in codons G12/13 (Exon 2), Q61, A59 (Exon 3), K117, and A146 (Exon\n             4)\n\n             Patient must agree to the collection of archival tumour tissue sample for biomarker\n             analysis. If an archived tumour sample is not available a fresh tumour biopsy can be\n             used.\n\n          4. Adequate organ system function as indicated by:\n\n               1. Absolute neutrophil count (ANC) ? 1.5 x 10^9/L\n\n               2. Platelets ? 100 x 10^9/L\n\n               3. Haemoglobin ? 9g/dL\n\n               4. Activated partial thromboplastin time (aPTT) ? 1.5 times the upper limit of\n                  normal (ULN)\n\n               5. Total bilirubin ? 1.5 mg/dL\n\n               6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 3.0 times\n                  the ULN if no liver involvement or ? 5 times the ULN with liver involvement.\n\n               7. Creatinine ? 1.5 times the ULN or creatinine clearance ? 60 mL/min as calculated\n                  by the Cockcroft-Gault method, or 24 hour measured urine creatinine clearance ?\n                  60 mL/min.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n\n          6. Life expectancy ? 12 weeks\n\n          7. Male patients with female partners of child-bearing potential must be willing to use\n             one highly effective form of contraception and must use a condom during their\n             participation in this study and for 7 months following the last dose of the study\n             drug. Male patients must refrain from donating sperm during their participation in the\n             study and at least for 7 months after the last treatment.\n\n          8. Female patients must use a highly effective contraceptive measure from screening until\n             18 weeks after the last dose of drug. All methods of contraception (with the exception\n             of total abstinence) should be used in combination with the use of a condom by a male\n             sexual partner for intercourse. Female patients should not be breast-feeding and must\n             have a negative pregnancy test prior to start of dosing if of childbearing potential\n             or must have evidence of non-childbearing potential by fulfilling one of the following\n             criteria at screening:\n\n        Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12\n        months following cessation of all exogenous hormonal treatment.\n\n        Documentation of irreversible surgical sterilisation by hysterectomy, bilateral\n        oophorectomy, or bilateral salpingectomy, but not tubal ligation.\n\n        Exclusion Criteria:\n\n          1. Patients who have received chemotherapy, radiotherapy, hormonal therapy, immunotherapy\n             or investigational drugs within 21 days or 5 half lives (whichever is shorter) from\n             enrolment.\n\n          2. With the exception of alopecia, any unresolved toxicities from prior therapy greater\n             than National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events\n             (CTCAE) Grade 1 at the time of enrolment.\n\n          3. Unresolved immunotherapy-related hepatotoxicity from previous therapy.\n\n          4. Major surgery (excluding placement of vascular access) ? 21 days from beginning of the\n             enrolment or minor surgical procedures ? 7 days. No waiting is required following\n             implantable port and catheter placement.\n\n          5. Patients receiving full-dose anti-coagulation therapies.\n\n          6. Has active or prior documented autoimmune disease within the past 2 years with the\n             exception of vitiligo, Grave's disease, and/or psoriasis not requiring systemic\n             treatment.\n\n          7. Has a history of atypical Haemolytic Uremic Syndrome.\n\n          8. Patients with leptomeningeal metastases.\n\n          9. Previously untreated brain metastases. Patients who have received radiation or surgery\n             for brain metastases are eligible if therapy was completed at least 3 weeks prior to\n             enrolment and there is no evidence of central nervous system disease progression or\n             mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.\n\n         10. Evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension, active bleeding diatheses, or active infection including hepatitis B,\n             hepatitis C and human immunodeficiency virus (HIV).\n\n         11. Any of the following cardiac criteria:\n\n               1. Congestive heart failure (CHF) per New York Heart Association (NYHA)\n                  classification > Class II.\n\n               2. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.\n\n               3. Unstable angina or new-onset angina.\n\n               4. QT interval (QTcF) >470 ms on screening electrocardiogram (ECG) by Fridericia's\n                  formula.\n\n         12. History of hypersensitivity to active or inactive excipients of AZD4785 or drugs with\n             a similar chemical structure or class to AZD4785.\n\n         13. Judgment by the Investigator that the patient should not participate in the study if\n             the patient is unlikely to comply with study procedures, restrictions and\n             requirements.\n\n         14. Psychological, familial, sociological, or geographical conditions that do not permit\n             compliance with the protocol.

Treatment with the following within the 4 weeks prior to the screening visit: radiotherapy, intralesional therapy; laser therapy surgery (other than biopsy) to the target area, local hyperthermia, levulinic acid, 5-fluorouracil, high potency corticosteroids (including systemic steroids), retinoids, diclofenac, hyaluronic acid, imiquimod;

Up to 5 of the 15 patients will be allowed to have had other approved or investigational drugs after prior progression of regorafenib monotherapy; (all patients enrolled in this trial must have had prior progression on regorafenib therapy); this may include TAS102, off-label therapy that may have been prescribed based on tumor genomic profiling or any investigational agents on a clinical trial

At least 3 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, whichever is shorter, after targeted or biologic therapy excepting prior treatment with CTLA 4, PD-1, or PD-L1 blocking antibodies for which only a 2 week interval is required. Patients with prostate cancer, unless orchiectomy has been performed in them, may continue to receive androgen deprivation therapy (ADT), anti-androgen therapy or therapy that interferes with androgenic stimulation.

Must be recovered from any reversible side effects of prior therapy (e.g. no major surgery, no antineoplastic or experimental therapy, or no significant radiation therapy to hematopoietic sites within 4 weeks of Baseline/C1D1, and no nitrosoureas or nitrogen mustards within 6 weeks of Baseline/C1D1)

At least one and up to two previous lines of systemic cytotoxic therapy for advanced NSCLC, of which one must have been a platinum-based doublet therapy. Up to four total previous lines of systemic therapy (including immunotherapy and molecularly targeted therapy)

One prior line of therapy is allowed.

Any prior anticancer therapy for this diagnosis

Other ongoing systemic therapy for cancer, including any other experimental treatment; these include concomitant therapy with any of the following: IL-2, interferon, ipilimumab, pembrolizumab, nivolumab, or other immunotherapy; cytotoxic chemotherapy; and targeted therapies

Prior biological cancer therapy, targeted therapy, or major surgery within 28 days prior to first dose of therapy

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, gamma-knife, other investigational agent) =< 14 days prior to the first dose of study drug; for WBRT, the washout period is 28 days; local treatment of isolated lesions for palliative radiation therapy (RT) (by radiotherapy, for example) is acceptable

In the investigator's opinion, is likely to require chemotherapy or surgical therapy for symptomatic disease management within 2 months of initiating androgen deprivation therapy;

Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma; an exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., chondrosarcoma); prior adjuvant therapy will not count provided it was completed more than 6 months previously

Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study

At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at any dose); systemic anti-malignancy therapy including systemic corticosteroid therapy of any dose is not allowed within 14 days prior to the required leukapheresis\r\n* NOTE: 30 days must elapse from the time of administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the principal investigator (PI) can stimulate immune activity and infusion of CAR T cells

Prior or ongoing systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)\r\n* CYP-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide, ARN-509)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Note: may be enrolled if has recently initiated hormone therapy (< 90 days duration); in the event that hormone therapy was initiated prior to study enrollment, the clock for 1 year of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment

Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last 12 months; (patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > 20% in the size; prior local therapy must be completed at least 4 weeks prior to the baseline scan)

Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm) or other radionuclide therapy.

Patients receiving prior therapy with HCQ

Patient with aggressive NHL must have received prior therapy – at a minimum:\r\n* Anti-CD20 monoclonal antibody unless tumor is CD20 negative and\r\n* An anthracycline containing regimen\r\n* Transformed FL must have had therapy for FL and be refractory to chemotherapy for DLBCL

Subjects who received combined androgen blockade as their first-line hormonal therapy with an antiandrogen must have shown PSA progression after discontinuing the antiandrogen for >= 6 weeks prior to study treatment; no washout is needed after abiraterone or enzalutamide are discontinued; first generation antiandrogens such as bicalutamide must be withdrawn if given as first-line therapy

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug (=< 21 days prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors (TKIs) [e.g., erlotinib, gefitinib and crizotinib] and =< 6 weeks for nitrosourea, mitomycin C, or bevacizumab). (If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics (PK) properties of an agent, a longer wash-out period may be required.)

Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug

Any approved anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, =< 3 weeks prior to first dose of study drug; however, the following are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)\r\n* Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1

Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)\r\n* Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1

Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Any prohibited prior or concomitant therapy

Prior chemotherapy, immunotherapy, radioactive, or biological cancer therapy (including monoclonal antibody [mAb]) within 28 days prior to registration

Patients must have failed at least one regimen of chemo or radiation therapy; NOTE: There is no limit to the number or types of prior therapy

Refractory disease is defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded.

Prior therapy for DLBCL, with the exception of nodal biopsy

Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.

Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.

Receipt of >/=1 but not more than 3 prior lines of therapy (Cohorts A, B, C, D1, E)

Receipt of >/=2 prior lines of therapy and progressed on treatment with an anti-CD38 monoclonal antibody and are refractory to both a PI and IMiD (Cohort D3)

Receipt of >/=4 lines of prior therapy and are refractory to the last line of treatment (Cohort F)

Prior treatment with anti-CD38 therapy including daratumumab (Cohorts D1, D2, E, F)

Prior therapy: eligible subjects must have had at least one line of platinum-based chemotherapy; this may be adjuvant therapy or first line of cytotoxic therapy for metastatic disease; prior hormonal therapy for metastatic/recurrent disease, prior targeted therapy, and prior radiotherapy are allowed; no maximum number of previous lines of chemotherapies; concomitant chemo-radiation is not considered as previous line of systemic chemotherapy

Prior therapy: there is no limit to the number of prior therapies provided all eligibility criteria are met; however, patients must have recovered from the acute toxic effects of all prior treatment\r\n* Patients must not have received prior therapy with either gemcitabine or nab-paclitaxel\r\n* Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 3 weeks of protocol therapy on this study\r\n* Hematopoietic growth factors: 7 days must have elapsed from the start of protocol therapy since the completion of therapy with filgrastim, and 14 days must have elapsed from the start of protocol therapy after receiving pegfilgrastim\r\n* Biologic (anti-neoplastic agent): 7 days must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent\r\n* Monoclonal antibodies: 3 half-lives must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody\r\n* Radiotherapy: 2 weeks must have elapsed from the start of protocol therapy since local palliative radiation therapy (XRT) (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if other substantial bone marrow irradiation was given\r\n* Stem cell transplant or rescue: no evidence of active graft versus (vs.) host disease and 2 months must have elapsed from the start of protocol therapy since transplant

One prior anti-cancer therapy that did not work

More than one line of anti-cancer therapy or no treatment at all

Previous first line therapy with at least radiotherapy

Participants with endometrioid histology and histologically confirmed expression of estrogen receptors (ER) and/or progesterone receptors (PgR) who have not received prior endocrine therapy and for whom endocrine therapy is currently indicated.

Receiving other experimental therapy

Completion of major surgery, chemotherapy, targeted therapy (such as everolimus or experimental agents or radiation within 14 days prior to starting investigational drug or has not recovered from major side effects; there is no required washout period from completion of prior anti-estrogen therapy (either scenario) or prior CDK 4/6 inhibitor (if scenario 2) to initiation of ribociclib/placebo and anti-estrogen on trial

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 21 days prior to the first dose of study drug

Patient must be either refractory to or relapsed after 1 line of therapy; prior radiation therapy is allowed

CELL PROCUREMENT: Received anti-CD19 antibody-based therapy OR cytotoxic chemotherapy not described as maintenance therapy within 2 weeks of procurement

Has progressed on prior therapy with lenalidomide

Patients receiving any concomitant systemic therapy for renal cell cancer are excluded

Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)

Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Any skin-directed therapy within 14 days prior to initiating protocol therapy

Prior systemic therapy with an anthracycline for any indication

Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior to registration or kinase inhibitor therapy =< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors

Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)

Completion of local therapy, such as radiation, surgical resection, injectable immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of protocol therapy.

Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of ABBV-181 or Rovalpituzumab Tesirine.

At least one prior systemic treatment (including neoadjuvant therapy) for their tumor of the small intestine, with intolerance to prior therapy, failure of the most recent therapy (of any line) or recurrent disease

Prior therapy with second line hormonal therapy is allowed (i.e. bicalutamide, nilutamide, flutamide, ketoconazole, abiraterone, enzalutamide, ARN-509)

Prior docetaxel as first line therapy in addition to androgen deprivation is allowed

Prior interferon or interleukin-2 therapy is NOT allowed

Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for the currently diagnosed cancer

Prior anti-tumor therapy within 3 weeks of cycle 1 day 1 (anti-tumor therapy defined as, but is not limited to, anti-cancer agents (cytotoxic chemotherapy, immunotherapy, and biologic therapy), radiotherapy, and investigational agents), the “wash-out period”

If patient has already started hormonal blockade therapy after radiation as adjuvant therapy, patient is eligible as long as the hormonal therapy was initiated no more than 6 months by the time of screening and can start the study drug within 4 weeks since the completion of screening.

A minimum of 2 weeks elapsed off of antiandrogen therapy prior to registration (i.e. flutamide, nilutamide, and bicalutamide) without evidence of an anti-androgen withdrawal response; an anti-androgen withdrawal response is a PSA level at 2 weeks (or more) off of anti-androgen equal or higher than PSA level when anti-androgen therapy stopped

Primary refractory (at least 1 prior line of therapy)

Responded to initial therapy for ? 1 year and relapsed after 2 or more lines of therapy, including an anti-CD20 monoclonal antibody

At least 1 prior line of therapy if primary refractory or relapsed within 1 year. Subjects who respond to initial therapy for greater than or equal to 1 year must have had at least 2 prior lines of therapy including an anti-CD20 monoclonal antibody.

Previously received at least one line of prior systemic therapy for metastatic disease; if the patient has a sensitizing EGFR mutation or ALK rearrangement, the patient must have received at least one prior targeted therapy for metastatic disease (ie, EGFR tyrosine kinase inhibitor [TKI] therapy or ALK TKI therapy, respectively); there is no limit on prior therapies allowed; patients must have completed previous treatment (including other investigational therapy) in greater than or equal to the following times prior to initiation of trial treatment:\r\n* Anti-cancer monoclonal antibody (mAb) therapy must be completed >= 3 weeks prior to trial treatment\r\n* Chemotherapy administered in a daily or weekly schedule must be completed >= 1 week prior to trial treatment\r\n* Chemotherapy administered in an every 2-week schedule must be completed >= 2 weeks prior to trial treatment\r\n* Chemotherapy administered in an every 3-week schedule must be completed >= 3 weeks prior to trial treatment\r\n* Targeted small molecule therapy must be completed >= 1 week prior to trial treatment OR\r\n* Have not received prior systemic therapy for their cancer in recurrent or metastatic setting, AND have a tumor with tumor proportion score (TPS) >= 50% as measured by 22C3 PD L1 immunohistochemistry (IHC) test, AND no evidence of a sensitizing EGFR mutation or ALK rearrangement

Tumor with mutation that is known to be sensitive to FDA approved targeted therapy but has not yet received such targeted therapy

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, radiotherapy or other investigational agent) =< 21 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C)

Patients must be at least 4 weeks from previous therapy (chemotherapy, hormonal therapy, and radiation therapy, immunotherapy and monoclonal antibodies, alternative therapy or investigational therapeutic agents); there is no limitation on the amount of prior therapies allowed; patients with ovarian cancer 4 weeks from previous therapy have been found to have normal monocyte function (unpublished)

Tumor with mutation that is known to be sensitive to FDA approved targeted therapy but has not yet received such therapy

Prior antiestrogen therapy

Prior treatment with neoadjuvant therapy

Participants in cohort C must have completed systemic therapy (4-6 cycles cisplatin or carboplatin + etoposides) and NOT be a candidate for consolidation thoracic radiotherapy or prophylactic cranial irradiation (PCI); participants in cohort C must initiate therapy with pembrolizumab within 6 weeks of the last dose of chemotherapy (therapy must not start within 2 weeks from the last dose); participants in cohort C must not have had progression of disease prior to the start of therapy

Participants in cohort A may not have had prior therapy for their disease; participants in cohort B may not have had more than 1 cycle of systemic therapy (cisplatin or carboplatin + etoposide); participants in cohort C and D should not have had more than one prior regimen of chemotherapy

Patient must have failed at least one prior therapy

Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy, including hematopoietic stem cell transplantation.

Had prior systemic therapy for pancreatic cancer

Currently receiving other anti-cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization)

At least 1 line of prior androgen receptor (AR) targeted therapy

Thrombocytopenia <100 x 103/ml, not resulting from therapy

Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer

Prior therapy exclusions:\r\n* Prior therapy with fulvestrant\r\n* Prior therapy with tamoxifen in the metastatic setting\r\n* More than 3 prior lines of endocrine therapy in the metastatic setting\r\n* More than one prior line of chemotherapy in the metastatic setting

Patients must have no more than one prior systemic therapeutic regimen. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. No prior anti-CTLA4 therapy. Prior anti PD-1 or anti-PDL-1 antibody therapy is acceptable.

Patients are excluded if they have had prior hepatic arterial embolization therapy

Prior therapies for metastatic melanoma are allowed, including chemo-, cytokine-, immuno, biological and vaccine-therapy as long as they did not include BRAFi, MEKi; prior ipilimumab or PD-1 directed therapy will be allowed with a washout period of 4 weeks and if all autoimmune adverse events have resolved to grade 1 (except endocrine abnormalities that require continuous replacement)

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, tyrosine kinase inhibitor, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 30 days prior to the first dose of study drug and within 6 weeks for nitrosourea, mitomycin C or intravesical therapy)

Consideration for neoadjuvant therapy

Need or plans for concomitant antineoplastic therapy (including surgery, cryotherapy, radiofrequency ablation, chemo-embolization, conventionally fractionated radiotherapy, stereotactic body radiation therapy, and hepatic artery chemotherapy) for the protocol treated lesions except at progression; adjuvant systemic therapy before and after the protocol therapy, and surgery or other ablative therapy is allowed for lesions appearing after enrollment to this protocol is allowed; at least 4 weeks must have passed since the last directed intervention to the protocol-treated lesion

Concurrent or planned use of any other anti-cancer systemic chemotherapy, biological therapy (including hormonal or immune therapy), radiation therapy, or live cancer vaccines

Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC or radiation therapy)

Patients must have not have received any prior therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) for the treatment of stage IV NSCLC; patients may have received prior adjuvant or neoadjuvant chemotherapy or chemotherapy given as part of a curative intent chemoradiotherapy approach for NSCLC, if the last administration of the prior regimens occurred at least 1 year prior to study entry

PHASES 1 AND 2: patient participants with AML that has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy, and are currently considered unfit for, or unlikely to respond to, cytotoxic chemotherapy

Patients have a history of prior therapy with carboplatin

Currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, and surgery and/or tumor embolization) or any investigational drug within 7 days of cycle 1/day 1, 14 days of cycle 1/day 1 for limited palliative radiation, and/or five half-live of an oral therapy\r\n* Corticosteroid therapy started at least 7 days prior to initiation of treatment (prednisone =< 10 mg daily or equivalent) is allowed as clinically warranted); topical or inhaled corticosteroids are permitted

Prior conventional antitumor therapy, other than steroids, radiation therapy (RT) or TMZ therapy given for glioblastoma

Patients who are receiving any other anticancer therapy

Patients must have an advanced solid tumor malignancy with no remaining standard treatment options or for whom single agent capecitabine is an acceptable therapy; patients with colorectal cancer must have progressed on at least one line of fluoropyrimidine containing therapy; receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting for all colorectal cancer patients unless either of these agents are otherwise contraindicated in the opinion of the treating physician; prior regorafenib or TAS-102 therapy is not required

Participant may have received prior investigational therapy (including immune therapy)

Prior or ongoing systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (for example [e.g.] leuprolide, goserelin, triptorelin, degarelix)\r\n* Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide, apalutamide)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)

Systemic anticancer therapy within 21 days of the first dose of study drug\r\n* All adverse events from prior systemic therapy must have either stabilized or returned to baseline

Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 4 weeks prior to the first dose of the study drugs (except ibrutinib for patients in cohort 3); NOTE: for patients on oral targeted therapies (such as ibrutinib, idelalisib, IPI-145, ACP-196), a wash-out of 3 days from cycle 1 day 1 is acceptable

Prior therapy with cabazitaxel or to other drugs formulated with polysorbate 80

Receipt of any anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within the last 6 months (mo) (before the first dose of durvalumab)

Any of the following within 3 weeks prior to initiating study treatment\r\n* Systemic biologic therapy\r\n* Monoclonal antibody\r\n* Chemotherapy\r\n* TSEB \r\n* Phototherapy\r\n* Other investigational therapy

NO prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer

Prior therapy with microtubule destabilizing agents for NSCLC (i.e. vinorelbine)

At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed within one year; subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody

Systemic steroid therapy unless for physiologic replacement

Recent prior therapy, defined as 1. Any non-monoclonal anti-cancer therapy within 14 days or 5 half-lives, whichever is longer, prior to the first dose of GSK3326595. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK3326595. Prior therapy with biologic agents (including monoclonal antibodies) is permitted so long as 28 days have elapsed since therapy and all therapy-related AEs have resolved to =< Grade 1, 2. Any radiotherapy within 14 days or major surgery within 28 days prior to the first dose of GSK3326595. For subjects in the GBM cohort, subjects must have completed radiation therapy at least 28 days prior to the first dose of GSK3326595. 3. Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide or abiraterone should be stopped 2 weeks prior to enrolment. Subjects with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Subjects with prostate cancer may also remain on low-dose prednisone or prednisolone [up to 10 milligram (mg)/day] and still be eligible for this study.

Patients should have discontinued therapy with imatinib, dasatinib, nilotinib, ponatinib, omacetaxine or other anti-leukemia therapy (except hydroxyurea) >= 48 hours prior to start of study therapy and recovered from any toxicity due to these therapies to grade =< 1; hydroxyurea may be received up to the time of enrollment and for the first 6 weeks of study treatment if necessary

Prior therapy with bosutinib or axitinib

Must have received at least one prior anti-angiogenic therapy (or inability to tolerate, as above) in the advanced or metastatic setting; prior cytokine therapy (eg, IL-2, IFN-alpha), vaccine therapy, or treatment with cytotoxics is also allowed but not any other drug specifically targeting T-cell co-stimulation or checkpoint pathways

PART 2 GROUP 1 INCLUSION CRITERIA:  A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies) and enrollment in this study, to allow recovery from the acute toxic effects of all prior anti-cancer therapy:\r\n* Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy\r\n* Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor\r\n* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent\r\n* Immunotherapy: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1; at least 42 days after therapy with a cellular immunotherapy or anti-cancer vaccine\r\n* Radiation therapy: At least 14 days after local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of metaiodobenzylguanidine (MIBG); >= 6 months must have elapsed from total body irradiation (TBI), craniospinal XRT or 50% radiation of pelvis\r\n* Stem Cell Transplant (SCT): At least 12 weeks after myeloablative therapy with autologous stem cell transplant (timed from start of protocol therapy); subjects must meet adequate bone marrow function definition (see organ function requirements, below) post-myeloablative therapy; patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet peripheral blood count criteria below\r\n* Subjects with prior treatment with compound/s with the same mode of action used in one of the treatment groups are eligible if they have not previously received prior treatment with BOTH agents in the combination

PART 2 GROUP 2A INCLUSION CRITERIA: A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies) and enrollment in this study, to allow recovery from the acute toxic effects of all prior anti-cancer therapy:\r\n* Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy\r\n* Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor\r\n* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent\r\n* Immunotherapy: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1; at least 42 days after therapy with a cellular immunotherapy or anti-cancer vaccine\r\n* Radiation therapy: At least 14 days after local palliative XRT (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 6 months must have elapsed from TBI, craniospinal XRT or 50% radiation of pelvis\r\n* SCT: At least 12 weeks after myeloablative therapy with autologous stem cell transplant (timed from start of protocol therapy); subjects must meet adequate bone marrow function definition (see organ function requirements, below) post-myeloablative therapy; patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet peripheral blood count criteria below\r\n* Subjects with prior treatment with compound/s with the same mode of action used in one of the treatment groups are eligible if they have not previously received prior treatment with BOTH agents in the combination

PART 2 GROUP 3 INCLUSION CRITERIA: A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies) and enrollment in this study, to allow recovery from the acute toxic effects of all prior anti-cancer therapy:\r\n* Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy\r\n* Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor\r\n* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent\r\n* Immunotherapy: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1; at least 42 days after therapy with a cellular immunotherapy or anti-cancer vaccine\r\n* Radiation therapy: At least 14 days after local palliative XRT (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of metaiodobenzylguanidine (MIBG); >= 6 months must have elapsed from TBI, craniospinal XRT or 50% radiation of pelvis\r\n* SCT: At least 12 weeks after myeloablative therapy with autologous stem cell transplant (timed from start of protocol therapy); subjects must meet adequate bone marrow function definition (see organ function requirements, below) post-myeloablative therapy; patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet peripheral blood count criteria below\r\n* Subjects with prior treatment with compound/s with the same mode of action used in one of the treatment groups are eligible if they have not previously received prior treatment with BOTH agents in the combination

PART 2 GROUP 1 EXCLUSION CRITERIA: Other concomitant therapies\r\n* Corticosteroids that were initiated for anti-tumor effect within seven days prior to initiation of protocol therapy\r\n* Investigational drugs\r\n* Anti-cancer agents\r\n* Hematologic growth factors\r\n* Radiation therapy

PART 2 GROUP 2A EXCLUSION CRITERIA: Other concomitant therapies\r\n* Corticosteroids that were initiated for anti-tumor effect within seven days prior to initiation of protocol therapy\r\n* Investigational drugs\r\n* Anti-cancer agents\r\n* Hematologic growth factors\r\n* Radiation therapy

PART 2 GROUP 3 EXCLUSION CRITERIA: Other concomitant therapies\r\n* Corticosteroids that were initiated for anti-tumor effect within seven days prior to initiation of protocol therapy\r\n* Investigational drugs\r\n* Anti-cancer agents\r\n* Hematologic growth factors\r\n* Radiation therapy

Eight weeks must have elapsed from the time of any antibody therapy that could affect an anti-cancer immune response, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) therapy, at the time the patient receives the preparative regimen to allow antibody levels to decline; Note: patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies

Prior radiation therapy, immunotherapy, chemotherapy or other investigational therapy given for prostate cancer

PHASE I: A minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation; in addition, recovery to grade =< 1 from all reversible toxicities related to prior therapy is required at study entry

UROTHELIAL CARCINOMA EXPANSION COHORT: Prior antiangiogenic therapy are permitted (2-week washout from therapy is required)

Progression during or after first line chemotherapy or chemoradiotherapy; prior maintenance therapy, targeted therapy, and immunotherapy are allowed; prior use of rovalpituzumab is allowed; immunotherapy or targeted therapy will not be considered as second line therapy

Bevacizumab® or other anti-angiogenic therapy.

Has undergone cytotoxic induction therapy

Not pregnant, or taking effective contraception before rapamycin therapy, during therapy and for 12 weeks after discontinuation of therapy

Patients at risk of pregnancy who are unwilling or unable to take effective contraception before rapamycin therapy, during therapy, and for 12 weeks after discontinuation of therapy

Have received 0-2 lines of cytotoxic chemotherapy for metastatic breast cancer; prior endocrine therapy and/or targeted therapy is allowed

Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS; hormonal therapy is permitted; for Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS; patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled

Patients must be either refractory to or relapsed after 1 line of therapy

Patient must be either refractory to or relapsed after 1 line of therapy

Concomitant therapy with any other anticancer therapy or chronic use of systemic corticosteroids.

Prior or ongoing systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (e.g. leuprolide, goserelin, triptorelin)\r\n* Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)

Prior therapy with lomustine

Prior therapy with bevacizumab

Prior systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)\r\n* CYP-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. abiraterone, enzalutamide)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Note: may be enrolled if hormone therapy was recently initiated of any kind (< 90 days duration); in the event that hormone therapy was initiated prior to study enrollment, the clock for 1 year of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment

No prior chemotherapy, targeted therapy, or immunotherapy for mesothelioma

Has received any prior anticancer therapy for mesothelioma (no prior chemotherapy, immunotherapy, or targeted therapy)

INCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Patients with non-small cell lung cancer that is metastatic or inoperable and who have been treated with at least one line of prior therapy or declined conventional therapy

Prior systemic therapy, radiation therapy, or surgery within the 28 days of starting study treatment; palliative radiotherapy to a limited filed or palliative cryoablation is allowed after consultation with the principal investigator, at any time during the study participation including screening

Patients must be appropriate candidates for letrozole therapy in any line of therapy or for fulvestrant for second line of therapy or beyond

Use of any of the following after transplantation and prior to starting study therapy for cohort 3:\r\n* Investigational agents/therapies\r\n* Anti-leukemic agents given as post-transplant maintenance therapy (e.g., subcutaneous or oral 5-azacytidine or FLT3 inhibitors for maintenance)

Prior therapy with ado-trastuzumab emtansine (patients who had prior trastuzumab or other HER2 targeted agents are eligible)

Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for prostate cancer hormonal therapy, and treatment with MVT-5873 and MVT-2163.

Prior antitumor therapy for glioma (other than steroids)

Planned treatment with TTFields therapy.

At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at any dose); systemic anti-malignancy therapy including systemic corticosteroid therapy of any dose are not allowed within 14 days prior to the required leukapheresis; NOTE: 60 days must elapse from the time of administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the principal investigator (PI) can stimulate immune activity and infusion of CAR T cells

Subjects must be willing to refrain from blood donations during study drug therapy and for 8 weeks after therapy

Patients who have had chemotherapy, immunotherapy or any targeted therapy within 7 days prior to anticipated SRS treatment date or those planning for systemic therapy within 7 days following the protocol treatment

Patients who have previously taken mebendazole as part of any experimental anti-cancer protocol, and have failed this therapy

For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* 28 days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measurable

Prior yttrium-90 therapy for patients in cohorts 1 or 2

Patients with history prior to transplant of progression on lenalidomide therapy

Prior anti-estrogen therapy within the last 5 years

Patients can have received up to 4 lines of systemic treatment; psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy

Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 28 days (6 weeks for nitrosoureas or mitomycin C, and 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment on Study Day 1 of Period A.

Prior therapy with TAS-102

Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest; vaccination will not take place until at least one line of standard chemotherapy is given

Currently receiving active therapy for other neoplastic disorders

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug 30 days prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors (TKIs) (e.g., erlotinib, gefitinib and crizotinib) and within 6 weeks for nitrosourea or mitomycin C

Expected to require any other form of systemic antineoplastic therapy while receiving pembrolizumab

Subjects must not have evidence of cerebellar dysfunction at baseline or during prior cytarabine therapy

Subjects must have had at least three lines of therapy for their disease, including a proteasome inhibitor and immunomodulatory drug (e.g., lenalidomide), with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period

PHASE I: Hormonal therapy directed at treatment for the cancer must be discontinued at least one week prior to enrollment; hormone replacement therapy for symptom management is permitted

PHASE II: Hormonal therapy directed at treatment for the cancer must be discontinued at least one week prior to enrollment; hormone replacement therapy for symptom management is permitted

Participants who have received prior therapy with other anti-CD37-targeting therapy.

Inclusion Criteria:\n\n        For a subject to be eligible for this study, she must meet all of the following criteria:\n\n          1. Female subjects 18 years of age or older\n\n          2. Subjects may be enrolled with previous histologically proven diagnosis of the\n             following:\n\n             a. Endometrial Cancer: Patients must have recurrent or persistent endometrial\n             carcinoma, which is refractory to curative therapy or established treatments.\n\n             i. Histologic diagnosis will be reviewed by the treating institution ii. Patients with\n             the following histologic epithelial cell types are eligible: Endometrioid\n             adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell\n             adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified,\n             mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma.\n\n             iii. Initial treatment may have included chemotherapy, chemotherapy and radiation\n             therapy, and/or consolidation/maintenance therapy; antiangiogenic therapy (e.g.\n             bevacizumab) as part of adjuvant therapy is allowed. Chemotherapy administered in\n             conjunction with primary radiation as a radio-sensitizer will be counted as a systemic\n             chemotherapy regimen.\n\n             iv. Patients should have received no more than two prior cytotoxic or non-cytotoxic\n             therapies for management of recurrent or persistent disease (excluding endocrine\n             therapies which will not count in the number of regimens)\n\n             b. Ovarian cancer: Patients must have recurrent or persistent ovarian, fallopian tube\n             or primary peritoneal cancer, which is refractory to established treatments.\n\n             i. Patients with the following histologic epithelial cell types are eligible:\n             Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear\n             cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise\n             specified.\n\n             ii. Patients must have received at least one prior platinum-based chemotherapeutic\n             regimen for the management of primary disease containing carboplatin, cisplatin, or\n             another organoplatinum compound.\n\n             iii. This initial therapy may have included high-dose therapy, consolidation, or\n             extended therapy administered after surgical or non-surgical assessment.\n\n             iv. Antiangiogenic therapy (e.g. bevacizumab) as part of adjuvant therapy is allowed.\n\n             v. Patients should have received no more than two prior cytotoxic or non-cytotoxic\n             therapies for management of recurrent or persistent disease\n\n             c. Cervix cancer: Subjects diagnosed with histologically confirmed squamous cell\n             carcinoma of the cervix.\n\n             i. Patients must have received at least one prior platinum based chemotherapeutic\n             regimen for the management of primary disease containing carboplatin, cisplatin or\n             another organoplatinum compound. The initial therapy may have included high-dose\n             therapy, consolidation or extended therapy administered after surgical or non-surgical\n             assessment. Antiangiogenic therapy (e.g. bevacizumab) as part of adjuvant therapy is\n             allowed. Chemotherapy administered in conjunction with primary radiation as a\n             radio-sensitizer will be counted as a systemic chemotherapy regimen.\n\n             ii. Patients should have received no more than two prior cytotoxic or non-cytotoxic\n             standard therapies for management of recurrent or persistent disease.\n\n             d. Other uterine cancers: Subjects diagnosed with other uterine cancers, such as\n             Leiomyosarcoma, and have received no more than two prior cytotoxic or non-cytotoxic\n             standard therapies for management of recurrent or persistent disease.\n\n          3. For Phase 2a only, all patients must express at least one FGFr 1, 2 or 3 amplification\n             (or mutation) from archived tissue or new biopsy. For non-amplified patients, approval\n             of the site coordinator or the sponsor is required prior to enrollment.\n\n          4. All patients must have measurable disease. Measurable disease is defined as at least\n             one lesion that can be accurately measured in at least one dimension (longest\n             dimension to be recorded). Each lesion must be ? 20mm when measured by conventional\n             techniques, including palpation, plain x-ray, CT, and MRI, or ? 10mm when measured by\n             spiral CT.\n\n          5. Life expectancy ? 3 months\n\n          6. Subject must be suitable for oral administration of study medication\n\n          7. Patients must have signed an approved informed consent and authorization permitting\n             release of personal health information.\n\n          8. Patient must have adequate:\n\n               1. Bone Marrow Function: Absolute neutrophil count (ANC) greater then or equal to\n                  1,500/mm3, equivalent to Common Toxicity Criteria (CTC) grade 1. Platelets\n                  greater than or equal to 100,000/mm3\n\n               2. Renal Function: Creatinine less than or equal to 1.5 x institutional upper limit\n                  normal (ULN), CTC grade 1. Note: If creatinine is greater than 1.5 x ULN,\n                  creatinine clearance must be greater than >50 mL/min.\n\n               3. Hepatic Function: Bilirubin less than or equal to 1.5 x ULN (CTC grade 1) or less\n                  than or equal to 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT less\n                  than or equal to 3.0 ×ULN.\n\n               4. Coagulation profile: PT such that international normalized ratio (INR) is ? 1.55\n                  (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of\n                  therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times\n                  control.\n\n          9. ECOG performance status ? 2.\n\n         10. Subjects of child-bearing potential must agree to use contraceptive measures starting\n             1 week before the administration of the first dose of AL3818 until 4 weeks after\n             discontinuing study drug.\n\n         11. Subjects of child-bearing potential must have a negative serum pregnancy test prior to\n             study entry and cannot be lactating.\n\n         12. Ability and willingness to comply with the study protocol for the duration of the\n             study and with follow-up procedures.\n\n        Exclusion Criteria\n\n        Subjects who meet any of the following criteria will be excluded from participation in the\n        study:\n\n          1. Subjects who have received prior treatment with an FGFr inhibitor or antagonist of\n             FGFr. Prior anti-VEGF or anti-angiogenic therapy is allowed in the adjuvant treatment\n             setting Prior anti-VEGF or anti-angiogenic therapy for the treatment of recurrent\n             disease is not allowed.\n\n          2. Patients who have received prior antiangiogenic therapy, including bevacizumab,\n             sorafenib, sunitinib, in the setting of advanced disease.\n\n          3. Patients with serious, non-healing wound, ulcer or bone fracture.\n\n          4. Patients with active bleeding or pathologic conditions that carry high risk of\n             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major\n             vessels.\n\n          5. Patient with history or evidence upon physical examination of CNS disease, including\n             primary brain tumor, seizures not controlled with standard medical therapy, any brain\n             metastases or history of cerebrovascular accident (CVA, stroke) transient ischemic\n             attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment\n             on this study.\n\n          6. However, patients with metastatic CNS tumors may participate in this trial, if the\n             patient is > 4 weeks from therapy completion (including radiation and/or surgery), is\n             clinically stable at the time of study entry and is not receiving corticosteroid\n             therapy.\n\n          7. Patients with proteinuria. Patients discovered to have a urine protein of 1+ on\n             dipstick or ? 30 mg/dl at baseline should undergo a 24-hour urine collection, which\n             must be an adequate collection and must demonstrate < 1000 mg protein/24 hr to allow\n             participation in the study.\n\n          8. Patients with clinically significant cardiovascular disease; this includes:\n             Uncontrolled hypertension; Myocardial infarction or unstable angina within 6 months\n             prior to registration; New York Heart Association (NYHA) Grade II or greater\n             congestive heart failure (Appendix F); Serious cardiac arrhythmia requiring\n             medication; Grade II or greater peripheral vascular disease (Appendix F).\n\n          9. Patients who are pregnant or nursing. To date, no fetal studies of AL3818 in animals\n             or humans have been performed. Therefore, AL3818 should not be administered to\n             pregnant women. Subjects will be apprised of the large potential risk to a developing\n             fetus. It is not known whether AL3818 is excreted in human milk. Because many drugs\n             are excreted in human milk, AL3818 should not be administered to nursing women. Women\n             of childbearing potential must agree to use contraceptive measures during study\n             therapy and for at least 3 months after completion of AL3818 therapy. Because many\n             drugs are excreted in human milk.\n\n         10. Patients with uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.\n\n         11. Hemoptysis within 3 months prior to first scheduled dose of AL3818.\n\n         12. Patients with acute or chronic liver disease, active hepatitis A or B with known\n             cirrhosis or liver dysfunction.\n\n         13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in\n             cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of AL3818\n             or a major surgical procedure within 28 days or minor surgical procedure performed\n             within 7 days prior to first scheduled dose of AL3818.\n\n         14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19\n             who cannot be switched to other alternative medications (See Appendix E).\n\n         15. Known history of human immunodeficiency virus infection (HIV).\n\n         16. Subjects with active bacterial infections (other than uncomplicated urinary tract\n             infection) and/or receiving systemic antibiotics.\n\n         17. Patients with other invasive malignancies, with the exception of non-melanoma skin\n             cancer, who had (or have) any evidence of other cancer present within the last 5 years\n             or whose previous cancer treatment contraindicates this protocol therapy.\n\n         18. History of non-malignant GI bleeding, gastric stress ulcerations, or peptic ulcer\n             disease within the past 3-months that in the opinion of the investigator may place the\n             patient at risk of side effects on an anti-angiogenesis product.\n\n         19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).\n\n         20. Intra-abdominal abscess within the last 3 months.\n\n         21. History of uncontrolled hypertension that is not well managed by medication, as\n             documented by 2 baseline evaluations taken one hour apart with systolic blood pressure\n             >160 mm or diastolic blood pressure >90 mm Hg pressure, or that in the opinion of the\n             investigator may place the patient at risk when taking a VEGF inhibitor.\n\n         22. Pre-existing uncontrolled hypertension as documented by 2 baseline BP readings taken\n             at least one hour apart, defined as systolic bloodpressure (BP) >160 mm Hg or\n             diastolic BP > 90 mm Hg pressure.\n\n         23. QTcF>470 msec on screening ECG.\n\n         24. A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family\n             history of Long QT Syndrome).\n\n         25. The use of concomitant medications that prolong the QT/QTc interval.\n\n         26. Baseline echocardiogram (within 2 months) with left ventricular ejection fraction\n             (LVEF) < 50%.\n\n         27. History of difficulty swallowing, malabsorption, active partial or complete bowel\n             obstruction, or other chronic gastrointestinal disease or condition that may hamper\n             compliance and/or absorption of AL3818.\n\n         28. History of pancreatitis and/or renal disease that includes histologically confirmed\n             glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy,\n             or other renal insufficiencies.\n\n         29. Treatment with an investigational agent within the longest time frame of either 5\n             half- lives or 30 days of initiating study drug.\n\n         30. Known recreational substance abuse.\n\n         31. Known hypersensitivity to anti-angiogenic agents.

Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents

Chemotherapy or hormonal therapy for anti-cancer treatment within 28 days prior to Cycle 1 Day 1.

No prior treatment for primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or surgery other than the anthracycline and cyclophosphamide chemotherapy with or without 5-fluorouracil; treatment for ductal carcinoma in situ is allowed, such as surgery, hormonal therapy and radiotherapy

Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents

Patients who are receiving concurrent non-protocol anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumor embolization) are to be excluded

Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy or investigational medicinal product (IMP) within 28 days of first trial drug intake for Phase Ia subjects, and any prior therapy for Phase Ib subjects. For subjects with rapidly growing tumors localized in the head and neck region or thorax where the treating physician cannot wait for 28 days, inclusion may take place if there is no residual toxicity from previous treatment (maximum CTCAE Grade 1)

Have relapsed or refractory MM after at least one line of therapy

Prior therapy with ceritinib

Prior therapy

Myelosuppressive therapy- At least 14 days must have elapsed since the administration of previous therapy. Six weeks must have elapsed from the administration of nitrosureas or mitomycin C. For patients with ALL on maintenance therapy, they may be eligible if 7 days have elapsed and they are recovered from the toxic effects of the chemotherapy. This restriction does not include intrathecal chemotherapy, which is permitted.

Any prior anticancer therapy

Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort

Receipt of any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of enrollment

Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or hormonal therapy).

Has been treated with anti-cancer therapy or thoracic radiation therapy within 14 days

Prior therapy(ies), if applicable, must be completed according to the criteria below:

Completing SoC adjuvant therapy per NCCN guidelines to include chemotherapy, radiation therapy, and/or biologic therapy as clinically indicated. (Consent #2 should be signed as close to completion of SoC as possible but may overlap completion by up to one month.)

Maintenance therapy during the first platinum-free interval is allowed; however, the last dose must have been at least 21 days prior to Randomization. No cancer vaccine therapy is allowed.

Patient has fully recovered from the acute toxic effects of chemotherapy, immunotherapy, or radiation therapy prior to entering this study:\r\n* Myelosuppressive chemotherapy: patient has not received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (4 and 6 weeks if prior temozolomide and nitrosourea, respectively)\r\n* Hematopoietic growth factors: at least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim\r\n* Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur\r\n* Monoclonal antibodies: at least three half-lives must have elapsed since prior therapy that included a monoclonal antibody\r\n* Radiation therapy: at least 3 months must have elapsed since any previous irradiation; unless measurable disease progression occurs at a site separate from the irradiated area and the patient has recovered from toxicities associated with radiation therapy

Subject has received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or herbal therapy within 7 days prior to the first dose of ABBV-399.

All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon >= 28 days before study entry

No prior chemotherapy in the recurrent setting; prior hormonal therapy is permitted; concomitant anti-neoplastic anti-hormonal therapy (including tamoxifen, aromatase inhibitors etc.) is not allowed for patients participating in study treatment; low-dose (physiologic) estrogen hormone-replacement therapy (HRT) may be given

Prior CAR therapy or other genetically modified T cells

Inadequate washout from prior therapy

Steroid therapy for anti-neoplastic intent within 5 days

Inclusion Criteria:\n\n        To be eligible for the study, patients must meet ALL of the following criteria prior to\n        enrollment in the study:\n\n          1. Must be ? 18 years of age at the time of consent.\n\n          2. Must have recurrent, metastatic, or persistent squamous cell carcinoma, adenosquamous\n             carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment\n             with surgery and/or radiation therapy and for which no other therapies are expected to\n             have significant benefit, in the opinion of the Investigator.\n\n          3. Must have at least 1 lesion that is resectable for TIL generation. The resected TIL\n             generating lesion(s) should yield at least 1.5 cm in diameter post-resection of tumor\n             tissue. Following resection for TIL generation, must have a remaining measurable\n             target lesion as defined by RECIST v1.1\n\n          4. Must have had at least 1 and no more than 3 prior systemic chemotherapeutic treatments\n             (such as carboplatin/cisplatin, paclitaxel, and bevacizumab except where there are\n             contraindications) for cervical carcinoma. Patients must have progressive disease\n             while receiving or after the completion of the most recent prior treatment.\n\n          5. Any prior therapy directed at the malignant tumor must be discontinued at least 28\n             days prior to tumor resection. Radiation therapy may have been received up to 28 days\n             prior to tumor resection for lesions not expected to be used for TIL generation or\n             target lesions.\n\n          6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n\n          7. Patients must be seronegative for the human immunodeficiency virus (HIV). Patients\n             with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core\n             antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic\n             infection may be enrolled if the viral load by polymerase chain reaction (PCR) is\n             undetectable with/without active treatment.\n\n          8. Patients of childbearing potential must be willing to practice an approved method of\n             birth control starting at the time of informed consent and for 1 year after the\n             completion of the study treatment regimen.\n\n        Exclusion Criteria:\n\n          1. Patients who have received an organ allograft or prior cell transfer therapy except\n             for prior LN-145 therapy.\n\n          2. Patients who are on a systemic steroid therapy > 10 mg of prednisone daily or other\n             steroid equivalent.\n\n          3. Patients who currently have prior therapy-related toxicities greater than Grade 1\n             according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia, or vitiligo\n             prior to enrollment/resection.\n\n          4. Patients who have a contraindication to or history of hypersensitivity reaction to any\n             component or excipients of the TIL therapy and the other study drugs.\n\n          5. Patients with active systemic infections, coagulation disorders or other active major\n             medical illnesses of the cardiovascular, respiratory, or immune system.\n\n          6. Patients with symptomatic and/or untreated brain metastases (of any size and any\n             number).\n\n          7. Patients who have any form of primary or acquired immunodeficiency syndrome, such as\n             severe combined immunodeficiency disease or acquired immune deficiency syndrome\n             (AIDS).\n\n          8. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.\n\n          9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New\n             York Heart Association (NYHA) Class 2 or higher.\n\n         10. Patients who have a forced expiratory volume in 1 second (FEV1) of less than or equal\n             to 60% of predicted normal.\n\n         11. Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD\n             regimen.\n\n         12. Patients whose cancer requires immediate treatment or who would otherwise suffer a\n             disadvantage by participating in this study.\n\n         13. Patients who have received prior treatment with immunotherapy (eg, anti-PD-1\n             anti-PD-L1, or anti-CTLA4 antibodies)

Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2).

Liver tumor-directed therapy, hepatic surgery, antibody-based therapy, or immunotherapy must not have been performed < 28 days, chemotherapy < 21 days, and targeted small molecule therapy or hormonal therapy < 14 days prior to enrollment.

Prior therapy: >= 3 weeks should have elapsed since last cytotoxic therapy, immunotherapy or radiation therapy; more than one week should have elapsed since major surgery

Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible

Concurrent bisphosphonate therapy is not excluded, however patients should not start bisphosphonate therapy while on this study; those patients already receiving bisphosphonate therapy should continue at the same dosing and schedule as prior to study entry

Any antibiotic therapy or evidence of infection within 1 week of registration

ARM B COHORT 3: Patients must have failed one prior line of systemic therapy for the treatment of advanced non-small cell lung cancer; prior adjuvant therapy with subsequent recurrence within 6 months of completion of therapy will count as one prior line of systemic therapy and such patients will be eligible

Patients must not have received any anti-cancer therapy (cytotoxic chemotherapy, targeted therapy or radiation) within the past 28 days prior to initiation of study therapy

ARM B COHORT 3: Patients must not have had more than one prior line of systemic therapy for advanced non-small cell lung cancer (including treatment with a targeted agent); prior adjuvant therapy completed more than 6 months prior to disease recurrence will not count as a prior line of systemic therapy for advanced disease

Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy; or severe pre-existing gastrointestinal (GI) disorder that requires peptidylprolyl isomerase (PPI) or histamine H2 (H2) receptor antagonist therapy be uninterrupted

Planned systemic therapy after orbital radiation therapy is permitted however the timing of systemic therapy will be recorded and patients will be stratified according to receipt of adjuvant systemic therapy

Chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of enzalutamide therapy; for patients with objectively progressive disease on a Bruton tyrosine kinase (BTK)-targeting agent whom in the opinion of the investigator would not tolerate a 21 day washout period, a > 5 half-lives washout period will be allowed

Ongoing treatment with hormonal agents (e.g. finasteride, dutasteride, ketoconazole, hormonal birth control, estrogen replacement therapy, testosterone replacement therapy) or herbal products that may have hormonal activity (saw palmetto, black cohosh); patients taking these agents are eligible for screening, but must be willing to undergo a washout period of 4 weeks prior to starting study treatment

All therapy (except hormonal therapy) directed at the malignant tumor must be discontinued at least 21 days prior to registration

Any hormonal therapy directed at the malignant tumor must be discontinued at least 7 days prior to registration; continuation of hormone replacement therapy is permitted

Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled 90Y therapy dose

No known effective therapy options are available

Previous therapy with regorafenib

More than three lines of prior therapy.

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol; patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication; any investigational drugs should be discontinued 2 weeks prior to the first dose of study medication and radiotherapy must have been completed >= 2 weeks prior to initiation of study drug (cycle 1, day 1)

Prior therapy with bevacizumab, liposomal doxorubicin, or everolimus

Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy are allowed provided therapy completed at least 1 year prior to enrollment\r\n* No prior talimogene laherparepvec or tumor vaccines allowed\r\n* No prior radiation to the same tumor bed allowed

Subject has any acute infection that requires specific therapy; acute therapy must have been completed within seven days prior to study enrollment

Is expected to require any other form of systemic or localized antineoplastic therapy while on study

Have had prior enzalutamide, ARN-509, or galeterone therapy

Use of hormonal therapy or androgen deprivation therapy, including enzalutamide, except in the following setting:

Patients can be on androgen deprivation therapy

No prior therapy for pancreatic cancer, including chemotherapy, radiation therapy, definitive surgery or investigational therapy

Any major surgery, radiotherapy, cytotoxic chemotherapy, biologic therapy, immunotherapy, immunomodulatory drugs, experimental therapy within 4 weeks prior to the first dose of the study drugs; Note: prior therapy with anti cluster of differentiation (CD)20 monoclonal antibody, anti CD52 monoclonal antibody, and lenalidomide are allowed; for oral targeted therapies (such as idelalisib, venetoclax), a washout of 3 days is allowed

Patients with previously treated B-cell ALL (relapsed and/or refractory after prior therapy)

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Any anti-cancer therapy within the past 21 days of the first day of treatment

ARM 1 SALVAGE COHORT: Patients with AML or biphenotypic or bilineage leukemia who have failed prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy will be eligible for Arm 1;

In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and nivolumab will be at least 2 weeks OR at least 5 half-lives for cytotoxic/noncytotoxic agents; the half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure’s, or drug-administration manuals) and will be documented in the protocol eligibility document; since the effect of both nivolumab and 5-azacytidine may be delayed; use of one dose of cytarabine (up to 2 g/m2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and during the study treatment; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted

Patients for who CEM (carboplatin, etoposide, melphalan) therapy is administered within 30 days prior to 131I-MIBG therapy or for whom this therapy is planned within 30 days following administration of 131I-MIBG

Prior anthracycline therapy does not exceed 200 mg/m^2 total cumulative dose

Prior systemic treatments for metastatic disease are permitted but may not be ongoing, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy

Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.

There must be no plans for the patient to receive other concomitant or post treatment adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy, conventionally fractionated radiotherapy, 2nd generation anti-androgen therapy (i.e. enzalutamide, abiraterone, etc.), or chemotherapy given as part of the treatment of prostate cancer

Patients may have used prior hormonal therapy, but it should be limited to no more than 9 months of therapy prior to enrollment

Any systemic anti-cancer therapy within 3 weeks prior to course 1 day 1 (C1D1) of study therapy\r\n* Exception is made for patients with EGFR or ALK re-arrangements who must have stopped TKI therapy at least 7 days prior to C1D1

Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.

Prior treatment of B-NHL with radiation therapy, non-standard systemic therapy, or antibiotics (in cases of MZL) within 21 days of the first dose of ixazomib

Patient must have completed any systemic therapy regimens (except an ALK inhibitor) and therapeutic radiation a minimum of 21 days prior to initiation of study therapy

Prior systemic therapy

Patients receiving prior therapy with RGF, VOR, and/or HCQ

Previous treatment with any anti-CD22 directed therapy

Must be at least 7 days since last chemotherapy or biologic therapy administered; for patients previously enrolled on this trial who had a usable T cell product generated but removed prior to receiving T cell therapy and are re-enrolling on the trial, the time from chemotherapy agent or biologic agent is not restricted

No prior genetically modified cell therapy that is still detectable or prior virotherapy

Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent

Prior therapy with ceritinib

Any history of systemic anti-cancer therapy (standard or experimental) completed within 30 days prior to dosing, with the exception of palliative ablation of lesion(s) as long as measurable disease lesion(s) remain for evaluation of exploratory endpoints

Subjects with any acute infection or severe or uncontrolled that requires systematic antibiotic therapy; acute therapy must have been completed at least seven days prior to study enrollment

Persistent or recurrent adenovirus infection or disease despite at least 7 days of standard therapy or failure of therapy as described below or if unable to tolerate standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function. i. Adenovirus infection: defined as the presence of adenoviral positivity as detected by polymerase chain reaction (PCR) or culture from ONE site, such as stool or blood or urine or nasopharynx. ii. Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, Direct fluorescent assay (DFA) or culture from two or more sites such as stool or blood or urine or nasopharynx. iii. Failure of therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR (or any other quantitative assay) after 7 days of antiviral therapy.

Chronic corticosteroid dependence (except replacement therapy)

Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol

Therapy with CPI-613 prior to participating in this trial

Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug

Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosourea, mitomycin-C, targeted therapy and radiation) =< 4 weeks prior to starting study drug

Anticancer therapy, monoclonal antibody or major surgery within 4 weeks prior to the first dose of MEDI4736\r\n* Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable

Newly-diagnosed chemo-naive or recurrent after curative-intent surgery\r\n* >= 6 months after completion of adjuvant therapy (including chemotherapy and/or radiotherapy)\r\n* No prior treatment with any targeted agent\r\n* Patients who have started first line mFOLFOX6 therapy (+/-trastuzumab for HER2 amplified tumors) may be considered for trial participation if they have received no more than 4 doses of therapy at the time of consent and screening\r\n** These patients will be required to meet ‘next cycle’ parameters for eligibility before commencing treatment on trial rather than being required to meet parameters as indicated below which is for previously untreated metastatic/recurrent patients

Patients must not have received prior anticancer therapy with bevacizumab, anti-CLTA-4, or anti-PD1 for renal cell carcinoma; patients receiving any concomitant systemic therapy for renal cell cancer are excluded

Persistent CMV infection despite optimum anti-viral therapy\r\n* Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates; OR \r\n* Failure of antiviral therapy: defined as the continued presence of deoxyribonucleic acid (DNA)emia (defined as >= 137 copies/ml by polymerase chain reaction [PCR]) for at least 2 weeks of CMV antiviral therapy; OR \r\n** Optimum therapy is defined as at least 14 days of therapy with ganciclovir, foscarnet, cidofovir, or valganciclovir for patients with disease or CMV viremia\r\n** Relapse while on CMV antiviral therapy defined as recurrence of DNAemia while being on at least 2 weeks of antiviral therapy OR\r\n* Patients who cannot tolerate standard anti-viral therapy and cannot continue anti-viral treatment due to side effect profile will be eligible independent of anti-viral therapy duration

Prior systemic therapy for pancreatic cancer

Previous chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of ibrutinib therapy or radio-immunotherapy within 12 weeks of initiation of ibrutinib therapy

Candidate for neoadjuvant endocrine therapy

Received any of the following for treatment of this cancer (except for the neoadjuvant endocrine therapy specified within this protocol):\r\n* Surgery\r\n* Radiation therapy\r\n* Chemotherapy\r\n* Biotherapy\r\n* Hormonal therapy\r\n* Investigational agent

Recovery from effects of any recent surgery, chemotherapy and/or radiation:\r\n* No evidence of active infection requiring antibiotic therapy\r\n* Hormonal therapy being utilized, as an anti-neoplastic treatment must be discontinued at least one week prior to study entry; hormonal replacement therapy for symptom management is allowed\r\n* Any prior therapy directed at the malignancy including biologic or immunologic agents, must have be discontinued at least three weeks prior to study entry

Treatment with any of the following anti-cancer therapies:\r\n* Radiation therapy, surgery, or tumor embolization within 14 days prior to the first dose of pazopanib OR\r\n* Chemotherapy, immunotherapy, investigational therapy, or hormonal therapy within 14 days prior to the first dose of pazopanib

Prior therapy with neural stem cells

Unwilling to undergo anti-endocrine therapy

Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT's were experienced. Prior therapy with other retinoids

Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy (excluding bone-directed therapy), prior to enrollment

No recent treatment for thyroid cancer as defined as:\r\n* No prior RAI therapy is allowed < 6 months prior to initiation of therapy on this protocol; a diagnostic study using < 10 millicurie (mCi) of RAI is not considered RAI therapy\r\n* No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol; (previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol)\r\n* No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy on this protocol

If newly diagnosed, prior therapy with hydrea and/or steroid and the use of a single or a two day dose of cytarabine (up to 3 g/m^2), for emergency use up to 24 hours prior to start of study therapy is allowed

Expected to require any other form of antineoplastic therapy while on study

Use of investigational agents within 30 days or any anticancer therapy within 2 weeks prior to entering this study with the exception of hydroxyurea; the patient must have recovered from all acute toxicities from any previous therapy

For frontline cohort: no prior potentially curative therapy for leukemia; prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, tretinoin (ATRA), or a total dose of cytarabine up to 2 g (for emergency use for stabilization) is allowed

Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study

More than 2 cycles of prior induction therapy for AML

Prior exposure to the investigational agent or anti-c-Met, anti-hepatocyte growth factor (HGF) or anti-vascular endothelial growth factor (VEGF) directed therapy within six months prior to study entry

Patients who received prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to day 1 of cycle 1; patients are permitted to be on dabrafenib and trametinib standard of care at start of therapy without wash-out period prior to day 1 of cycle 1; dosing will change to protocol determined dose levels on day 1 of cycle 1

Prior seizures while on enzalutamide therapy

PHASE II -- Patients aged 60 and older with newly diagnosed primary or secondary AML according to WHO classification, without any prior therapy for AML with the exception of (a) emergency leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before start of the trial treatment; Note: prior therapy for preexisting hematological condition e.g. MDS or myeloproliferative disease (MPD), including but not limited to hypomethylating agents is allowed until at least 2 weeks have elapsed from completion of that agent before the first dose of MEK 162; patients with relapsed AML, and relapsed MDS and CMML, after prior hypomethylating therapy are also eligible to participate

PHASE I and II -- Administration of any antineoplastic therapy within at least 4 weeks (cytotoxic chemotherapy) or 2 weeks (biological and targeted therapy; hypomethylating agents are considered to be biological therapy) of that therapy of the first MEK 162/MEK 162 dose; except the use of hydroxyurea which can be administered up to 5 g/day up to 24 hours before the initiation of the study drug

Treatment for malignancy with anticancer therapy, including cytotoxic agents, hormonal agents, or immunotherapy, within 5 years of enrollment

Receipt of Gliadel therapy

Prior therapy for melanoma that may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or ?2 different regiments of systemic chemotherapy, targeted therapy, or other experimental systemic therapies. Prior treatment with immune checkpoint inhibitors is not allowed.

Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy

Ongoing treatment with cytotoxic therapy

Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study

Patients who have had prior therapy with gemcitabine or docetaxel

Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible (Turnstile I)

More than one prior systemic therapy regimen for metastatic pancreatic cancer (radiosensitizing doses of 5-FU or gemcitabine at the time of initial radiotherapy do not count as a prior systemic therapy regimen)

Hormonal therapy, radiation therapy, biologic therapy, chemotherapy or other systemic antitumor therapy for pancreatic cancer within 14 days prior to Cycle 1 Day 1

Diagnosis of stage 0-III breast cancer within 12 years prior to enrollment; all indicated surgery, chemotherapy, and/or radiation therapy must have been completed at least 12 weeks prior to enrollment; concomitant endocrine therapy and targeted therapies such as palbociclib, pertuzumab, and trastuzumab are permitted

HER2 therapy naive or currently receiving non-lapatinib HER2 targeted therapy

Histologically or cytologically documented MDS of any risk group that has failed previous therapy (therapy failure is defined as patients who have been sufficiently treated with previous agents without response in the opinion of the treating physician, or whose disease has progressed or relapsed while on a hypomethylating agent)

All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed

RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed

For Phase I Only: Refractory or relapsed disease defined as follows: Patients with MDS or CMML should have failed prior therapy (e.g., with a hypomethylating agent, clofarabine, and/or with lenalidomide); Patients with AML should have failed any prior induction therapy or have relapsed after prior therapy; Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML; Patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive standard intensive therapy (ie, high-dose cytarabine-based chemotherapy).

For Phase I and II: Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the toxic effects of that therapy to at least grade 1. Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. The additional days of Hydrea after 28 is permitted as clinically indicated, on case by case basis after discussion with the PI. Other agents given transiently with the intention to control rapid proliferation such as 1-2 doses of single agent ara-C or few doses of sorafenib are also allowed.

Concomitant use of any anti-cancer therapy or radiation therapy

INCLUSIONS FOR CAR-T CELL THERAPY

EXCLUSIONS FOR CAR-T CELL THERAPY

Cytokine therapy (e.g. filgrastim [G-CSF], sargramostim [GM-CSF], interleukin [IL]-6, IL-2): must be discontinued a minimum of 24 hours prior to MIBG therapy

Prior gene therapy

Tetanus vaccine during therapy or within 1 week prior to enrollment

Relapsed or refractory to the most recently received therapy; refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion

Systemic immunoglobulin therapy within the last 30 days

Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee

Patients who have completed previous therapies 4-weeks prior to (or within 5 drug half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks. This includes an exception of patients with metastatic GIST tumors who are taking maintenance imatinib mesylate therapy. These patients are allowed to remain on imatinib mesylate therapy up to enrollment in this study.

For cohort of patients that are already on ruxolitinib therapy: on therapy with ruxolitinib for at least for 6 months, and on stable dose for last 2 months, before starting therapy with sotatercept

Hormonal therapy within 1 week

Any prior therapy for the treatment of pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational).

Prior therapy with any hypoxic cytotoxin (hypoxia-targeting drugs).

Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy, was less than 14 days prior to protocol therapy (radiation and veliparib)

For purposes of this protocol, anti-tumor treatment may be defined as, but is not limited to, anti-cancer agents (cytotoxic chemotherapy, immunotherapy, biologic therapy), radiotherapy, and investigational agents; an investigational agent is any drug or therapy not currently approved for use in humans\r\n* Anti-cancer agents: anti-cancer agents are not permitted within 21 days prior to start of POPI; there are no limitations on the type or number of prior regimens; hormonal therapy and trastuzumab are permitted during POPI\r\n* Radiation: prior treatment with breast irradiation is not allowed \r\n* Surgery: incident breast biopsies only permitted prior to POPI to confirm residual disease after NAC

Treatment with any of the following anti-cancer therapies: \r\n* Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR\r\n* Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib \r\n* Any prior treatment with pazopanib or vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)-targeting agents (eg. sorafenib, sunitinib, and bevacizumab) \r\n* Any prior treatment with gemcitabine

Dermatology evaluation with excision of any suspicious lesions prior to initiation of therapy

Prior therapy with pomalidomide

Other concomitant anti-cancer therapy except corticosteroids

No more than 2 prior chemotherapies and 1 relapse; prior bevacizumab therapy is allowed

PHASE I: Patients may have had treatment for any number of prior relapses; relapse is defined as progression following initial therapy (i.e. surgery and radiation +/- chemotherapy [chemo] if that was used as initial therapy)

PHASE II: Patients may have had treatment for no more than 1 prior relapse (i.e. failed 2 lines of treatment-initial therapy and therapy for first relapse) at 2nd relapse, treatment per BTTC09-01 is an option; relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy); the intent therefore is that patients had no more than 2 prior therapies (initial and treatment for 1 relapse); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse; for patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse

1) Subject has [follicular lymphoma that has progressed within 24 months of first diagnosis and treatment with combination chemoimmunotherapy] (e.g. R-bendamustine, R-CHOP) OR Progression of iNHL within 6 months of completion of second or later line therapy containing both an anti-CD20 antibody and alkylating agent OR Progression of iNHL at any point following autologous transplantation. 2) Subject has [measurable disease]. 3) Subject has no known presence or history of CNS involvement by lymphoma. 4) If subject is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, subject is able to stop conventional therapy 2 weeks or 5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to planned leukapheresis. 5) Subject has ECOG performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function 6) Subject is not pregnant or breastfeeding (female subjects only) and is willing to use birth control from the time of consent through 6 months following CAR T cell infusion (both male and female subjects).B24

Patients who have received systemic cytotoxic chemotherapy or approved oral targeted therapy or immunotherapy for 2 weeks, or other investigational agents for 3 weeks (4 half-lives for any oral targeted agents), or radiotherapy to a non-brain site for 2 weeks before initiation of IPdR therapy; patients who have recovered from serious (Common Terminology Criteria for Adverse Events [CTCAE] grade 3 or more higher) to grade 1 or less adverse events from the previous therapies are eligible; prior/current/future hormonal therapy and/or bisphosphonates are permitted with no minimum interval to initiation of study therapy; if indicated, patients can receive palliative radiation therapy to a non-brain site concurrent or immediately post-study treatment with no minimum interval to initiation of study therapy

Participant has received prior therapy for MDS. (Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy.)

Phase II IMT naive cohorts: Patients have not received systemic cytotoxic or immune-based therapy for advanced melanoma. BRAF and/or MEK inhibition therapy is acceptable before immunotherapy where clinically indicated. Other systemic cytotoxic or targeted therapy in the advanced setting is not permitted in this subset

Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see #5 below).

RAI-avid lesion on a radioiodine scan (a diagnostic, post-therapy, or post-ablation scans) performed =< 24 months prior to registration, which suggests that therapy with 131I is justifiable in the judgment of the investigator

131I therapy =< 6 months prior to registration; Note: 131I administered solely for diagnostic purposes is not considered 131I therapy

For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.

Other anti-cancer or investigational therapy while patients are on study therapy

Prior therapy with romidepsin

Prior intrapleural therapy (except pleurodesis) or intrapleural therapy at the time of P/D (i.e.: intrapleural chemotherapy, photodynamic therapy, intrapleural betadine)

Patients must be at least 3 weeks past any prior surgery, cytotoxic, chemotherapy, other immunotherapy, hormonal therapy, or radiation therapy; patients having been treated with monoclonal antibodies may enter the trial after a specified period of time (2 times the mean half-life of the agent); patients must have recovered from any toxicity of prior therapy prior to enrolling on study except for neuropathy where patients need to recover to less than grade 2

Previous systemic chemotherapy or non-radiation local therapy (such as surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) is allowed; the lesion must however have shown criteria of progression based on RECIST; local therapy must be completed at least 4 weeks prior to the baseline scan; this is to create a safer treatment environment and to help determine the effect of treatment by SBRT alone; patients will be allowed to go onto appropriate systemic therapy, as determined by their medical oncologist, 2 weeks following delivery of SBRT

Patient must either have recurrence of ICGCT or should be refractory to initial therapy

Corticosteroid therapy and endocrine replacement therapy (L-thyroxine, testosterone, estrogen, desmopressin acetate [DDAVP]) are permissible; any patient already receiving human growth replacement therapy should discontinue this prior to commencing chemotherapy, and should not restart until 3 years from diagnosis

Patients on Strata C and D must have recovered from the toxic effects of prior therapy to grade 1 or better; patients must be at least 3 weeks form the last dose of standard cytotoxic chemotherapy or myelosuppressive biological therapy, at least 1 week from the last dose of non-myelosuppressive biologic therapy and at least 6 months from placement of bis-chloroethylnitrosourea (BCNU) wafers; any questions related to the definition of non-cytotoxic agents should be directed to the principal investigator

Chemotherapy, radiation therapy, or biologic therapy (except trastuzumab) within 28 days prior to initiating treatment on study; endocrine therapy and supportive therapy with bisphosphonates will be allowed

PSA Doubling time < 10 months after local therapy in patients who have not had any previous hormone therapy

Patients must be at least 2 weeks from prior systemic therapy, radiation therapy, major surgery, or other investigational therapy, and have recovered from clinically significant toxicities of these prior treatments

Patients with relapsed disease are eligible if they have had no more than one prior therapy

Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee as to suitable eligibility (Turnstile I)

Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation

documented progression on the most recent line of therapy

Prior treatment with a Mucin 16 (MUC16)-targeted therapy

Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery.

Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I-metaiodobenzylguanidine): ?42 days after systemically administered radiopharmaceutical therapy.

Have documented evidence of progressive disease (PD) on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [eg, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).

Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy

Must have previously received at least 1, but no more than 2, lines of novel androgen receptor (AR)-targeted therapy (for example, abiraterone acetate with prednisone, enzalutamide, apalutamide) for prostate cancer. Participants must have had at least 4 weeks of AR-targeted therapy

Patient has received anticancer chemotherapy, TKIs, biologics, immunotherapy, radiotherapy, or investigational treatment within 15 days. (There is no washout for hormonal therapy for breast cancer).

Any therapy =< 2 weeks prior to registration; NOTE: Exception: patients on ibrutinib or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion; corticosteroids can be tapered to lowest possible dose after start of treatment at investigator discretion

More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma

Serious, uncontrolled infection requiring systemic antibiotic, antifungal or antiviral therapy. Prophylactic antibiotic, antifungal and/or antiviral therapy is permitted

Plans for the patient to receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol except at disease progression

Prophylactic anti-infective therapy, which is given without clinical symptoms is allowed.

Prior therapy with docetaxel

Criteria 4 Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy, see Appendix E for guidance)

Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody treatment-free interval from last dose received until first study treatment

Receipt of any systemic anticancer therapy within 28 days prior to the first dose of MEDI5083

Tissue Procurement Inclusion Criteria:\n\n        Subjects will be eligible for tissue procurement for the Vigil manufacturing process, if\n        they meet all of the following criteria:\n\n          1. Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous, clear\n             cell, or endometrioid ovarian, fallopian tube or primary peritoneal carcinoma\n\n          2. Age ? 18 years.\n\n          3. Estimated survival ? 6 months.\n\n          4. ECOG Performance Status ? 1\n\n          5. Metastatic disease\n\n          6. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative\n             resection or thoracentesis) and expected availability of a cumulative soft-tissue mass\n             of ~10-30 grams tissue (\grape\ to \golf-ball\ size) or ascites fluid estimated volume\n             ? 500mL (from a primary or secondary paracentesis, yielding in a high volume of tumor\n             cells) for immunotherapy manufacture.\n\n          7. Tumor intended for immunotherapy manufacture is not embedded in bone and does not\n             contain luminal tissue (e.g. bowel, ureter, bile duct).\n\n          8. Presence of at least one additional site of disease that is RECIST 1.1\n             evaluable/measurable.\n\n          9. Ability to understand and the willingness to sign a written informed protocol specific\n             consent for tissue harvest or a parental/guardian informed consent and pediatric\n             assent when appropriate.\n\n        Tissue Procurement Exclusion Criteria:\n\n        Subjects meeting any of the following criteria are not eligible for tissue procurement for\n        the Vigil manufacturing:\n\n          1. Medical condition requiring any form of chronic systemic immunosuppressive therapy\n             (steroid or other) except physiologic replacement doses of hydrocortisone or\n             equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily)\n             for < 30 days duration.\n\n          2. Known history of other malignancy unless having undergone curative intent therapy\n             without evidence of that disease for ? 3 years except cutaneous squamous cell and\n             basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other\n             in situ cancers are allowed if definitively resected.\n\n          3. Brain metastases unless treated with curative intent (gamma knife or surgical\n             resection) and without evidence of progression for ? 2 months.\n\n          4. Any documented history of autoimmune disease with exception of Type 1 diabetes on\n             stable insulin regimen, hypothyroidism on stable dose of replacement thyroid\n             medication, vitiligo, or asthma not requiring systemic steroids.\n\n          5. Known HIV or chronic Hepatitis B or C infection.\n\n          6. Known history of allergies or sensitivities to gentamicin.\n\n          7. History of or current evidence of any condition (including medical, psychiatric or\n             substance abuse disorder), therapy, or laboratory abnormality that might confound the\n             results of the study, interfere with the patient's participation for the full duration\n             of the study, or is not in the best interest of the patient to participate, in the\n             opinion of the treating Investigator.\n\n        Study Enrollment Inclusion Criteria:\n\n        Subjects will be eligible for registration into the trial if they meet all of the following\n        inclusion criteria:\n\n          1. Successful manufacturing of at least 4 vials of Vigil.\n\n          2. One of the following:\n\n               1. Failure to meet the eligibililty criteria for Protocol CL-PTL-119 due to i)\n                  histology of ovarian cancer and failure to achieve a complete clinical response\n                  following primary debulking surgery and standard paclitaxel/carboplatin therapy\n                  OR, ii) a histologic diagnosis of another gynecologic malignancy which is not\n                  ovarian cancer.\n\n               2. Recurrent ovarian cancer.\n\n               3. Randomized on Protocol CL-PTL-119 and were subsequently unblinded at recurrence\n                  and were assigned to the placebo arm.\n\n          3. ECOG performance status (PS) ? 1\n\n          4. Estimated survival ? 6 months.\n\n          5. Measureable or evaluable disease.\n\n          6. Adequate organ and bone marrow function as defined below:\n\n               1. Absolute neutrophil count (ANC) ? 1.5 × 10e9/L (1500 per mm^3)\n\n               2. Platelets >100 × 10e9/L (100,000 per mm^3)\n\n               3. Hemoglobin ?9.0 g/dL (5.59 mmol/L)\n\n               4. Creatinine clearance (CrCL) >50 mL/min by the Cockcroft-Gault formula or by\n                  24-hour urine collection for determination of creatinine clearance:\n\n                  Females:\n\n                  CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL)\n\n               5. Serum bilirubin ?1.5 × upper limit of normal (ULN). This will not apply to\n                  patients with confirmed Gilbert's syndrome (persistent or recurrent\n                  hyperbilirubinemia that is predominantly unconjugated in the absence of evidence\n                  of hemolysis or hepatic pathology) who will be allowed in consultation with their\n                  physician.\n\n               6. AST and ALT ?2.5 × ULN in patients with no liver metastasis\n\n               7. AST or ALT ?5 × ULN in patients with liver metastasis\n\n               8. TSH within institutional limits. If TSH is greater or less than institutional\n                  limits patients may participate if their T4 is within normal limits (WNL);\n                  patients may be on a stable dose of replacement thyroid medication; dose\n                  adjustments are allowed if needed\n\n          7. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated\n             with prior therapy or surgery\n\n          8. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to\n             CTCAE Grade 2 or better\n\n          9. Patients with irreversible toxicity that is not reasonably expected to be exacerbated\n             by the IPs may be included (e.g., hearing loss) after consultation with the Principal\n             Investigator\n\n         10. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,\n             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal\n             antibodies, other investigational agent) prior to tissue procurement and at least 21\n             days prior to the first dose of study drug (at least 21 days prior to the first dose\n             of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib\n             and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).\n\n         11. Subjects who are not rendered surgically sterile as a result of surgery for ovarian\n             cancer, must have, negative urine or serum pregnancy test. If the urine test is\n             positive or cannot be confirmed as negative, a negative serum test will be required\n             for study entry.\n\n         12. Ability to understand and the willingness to sign a written informed protocol specific\n             consent.\n\n         13. Willing and able to comply with the protocol for the duration of the study including\n             undergoing treatment and scheduled visits and examinations including follow up.\n\n        Study Enrollment Exclusion Criteria:\n\n        Subjects will NOT be eligible for study registration and enrollment if meeting any of the\n        following criteria:\n\n          1. Have received more than two additional chemotherapy regimens for recurrent ovarian\n             cancer, after their initial treatment with paclitaxel/carboplatin, OR have received\n             more than two additional chemotherapy regimens for the treatment of another\n             gynecologic malignancy\n\n               1. Patients must have fully recovered from chemotherapy associated toxicities prior\n                  to starting treatment on this protocol.\n\n               2. Palliative radiotherapy is permitted provided:\n\n             i. More than 3 weeks have elapsed between the end of radiotherapy and the first dose\n             of study therapy, AND ii. The lung is not in the radiation field, AND iii. The\n             irradiated lesion(s) cannot be used as target lesions.\n\n          2. Participation in another clinical study with an investigational product within the\n             last 3 weeks prior to study start.\n\n          3. Patients with autoimmune diseases are excluded from enrollment with the exception of\n             patients with hypothyroidism on stable thyroxine replacement, and patients with T1DM\n             on stable insulin replacement.\n\n          4. Receipt of steroid therapy within the 2 weeks of the first dose of study therapy.\n\n          5. Live vaccine used for the prevention of infectious disease administered < 30 days\n             prior to the start of study therapy. NOTE: Subjects, if enrolled, should not receive\n             live vaccine during the study and for 5 months after the last dose of atezolizumab.\n\n          6. Post-surgery complication that in the opinion of the treating investigator would\n             interfere with the subject's study participation or make it not in the best interest\n             of the subject to participate.\n\n          7. Mean QT interval corrected for heart rate (QTc) ?470 ms calculated from 3\n             electrocardiograms (ECGs) using Frediricia's Correction.\n\n          8. Female subjects who are pregnant, breast-feeding or of reproductive potential who are\n             not employing an effective method of birth control defined in the protocol. Effective\n             contraception is required for women receiving atezolizumab for 5 months after the last\n             dose.\n\n          9. Any condition that, in the opinion of the investigator, would interfere with\n             evaluation of study treatment or interpretation of patient safety or study results.

thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;

failed primary induction therapy with no complete remission and for whom no other approved therapy is available, and no more than 1 prior salvage therapy

No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)

No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)

?3 weeks for local radiation therapy, systemic cytotoxic anticancer therapy, treatment with other anti-neoplastic investigational agents

Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression.

Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists

Inclusion Criteria:\n\n        Note: No waivers of the study inclusion or exclusion criteria will be granted.\n\n          1. Diagnosis of a solid tumor for which the accepted standard of care includesa licensed\n             anti-EGFR therapy;\n\n          2. Tumor progression in patients with RAS wild type metastatic colorectal cancer\n             irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR\n             antibodies; OR Tumor progression in patients with metastatic colorectal cancer\n             refractory to cetuximab or panitumumab or other anti-EGFR antibodies OR Tumor\n             progression in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have\n             refused therapy.\n\n             OR Tumor progression or recurrence in patients with squamous cell carcinoma of the\n             head and neck irrespective of their exposure to licensed anti-EGFR therapy including\n             anti-EGFR antibodies.\n\n             OR Patients with locally advanced or metastatic colorectal carcinoma who have\n\n               1. relapsed after standard of care treatment,\n\n               2. proved refractory to standard of care treatment\n\n               3. refused standard of care treatment\n\n               4. been found to be medically unsuitable for standard of care treatment\n\n          3. Completion of written informed consent procedure;\n\n          4. Male or female subjects over 17 years of age\n\n          5. Life expectancy of at least 3 months;\n\n          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2;\n\n          7. At least one measureable non-irradiated site of disease according to Response\n             Evaluation Criteria in Solid Tumors (RECIST) version 1.1;\n\n          8. Adequate bone marrow function, with absolute neutrophil count (ANC) >1,500/mm3,\n             platelet count >100,000/mm3, and hemoglobin > 10 g/mm3;\n\n          9. Adequate liver function, with bilirubin <1.5 x the upper limit of the normal range\n             (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x the\n             ULN;\n\n         10. Adequate renal function, with serum creatinine <1.5 mg/dL;\n\n         11. Adequate cardiac function, with left ventricular ejection fraction (LVEF) ?50%, normal\n             electrocardiogram, and absence of significant cardiac disease;\n\n         12. In women of childbearing potential (defined as women of reproductive capacity who are\n             pre-menopausal or within 12 months of cessation of menses): negative serum pregnancy\n             test and use of an acceptable non-hormonal method of contraception;\n\n         13. Ability to communicate with the investigator, and understand and comply with the\n             requirements of the protocol;\n\n         14. Agrees to notify the investigator when deviating from the protocol requirements with\n             regard to concomitant medications;\n\n         15. Agrees to stay in contact with the study site for the duration of the study and to\n             provide updated contact information as necessary, and has no current plans to move\n             from the study area for the duration of the study.\n\n        Exclusion Criteria:\n\n          1. Participation in a study of an investigational agent or use of an investigational\n             device at the time of screening or within 4 weeks of enrollment;\n\n          2. Receipt of treatment with a monoclonal antibody (mAb) within 4 weeks of enrollment or\n             not recovered from an adverse event (i.e., event is >Grade 1 or subject has not\n             returned to baseline) due to treatment with a mAb administered >4 weeks before\n             enrollment;\n\n          3. Receipt of chemotherapy, targeted small molecule therapy, or radiation therapy within\n             2 weeks prior to enrollment, or not recovered from an adverse event (i.e., event is\n             >Grade 1 or subject has not returned to baseline) due to a previously-administered\n             agent;\n\n          4. Major surgical procedure or significant traumatic injury within 4 weeks prior to\n             screening;\n\n          5. Diagnosis of an additional malignancy that is progressing and requires treatment;\n             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the\n             skin, and in situ cervical cancer that has undergone potentially curative therapy;\n\n          6. Active autoimmune disease requiring systemic treatment within the past 3 months, or a\n             documented history of severe autoimmune disease, or a syndrome that requires systemic\n             steroids or immunosuppressive agents (subjects with vitiligo or resolved childhood\n             asthma/atopy are allowed);\n\n          7. Diagnosis of an immune deficiency;\n\n          8. Receipt of systemic steroids or any form of immunosuppressive therapy within 7 days\n             prior to enrollment, with the following exceptions:\n\n               1. Stable doses of topical, ocular, intranasal or inhaled corticosteroids\n\n               2. Doses of systemic steroids that, in the opinion of the investigator, are\n                  pysiologic replacement doses\n\n               3. Systemic steroids as prophylactic treatment for subjects with allergy to contrast\n                  media\n\n               4. Non-absorbed intra-articular steroid injections\n\n               5. Systemic corticosteroids required for control of infusion reactions or AEs if\n                  doses have been tapered to <10 mg prednisone or equivalent for 2 weeks prior to\n                  the first study treatment\n\n          9. Evidence of interstitial lung disease or active, non-infectious pneumonitis;\n\n         10. Active infection requiring systemic therapy;\n\n         11. History of cerebrovascular accident, transient ischemic attack, or subarachnoid\n             hemorrhage within 6 months prior to screening;\n\n         12. Active hepatitis B (i.e., hepatitis B surface antigen [HBsAg] positive) or hepatitis C\n             (i.e., hepatitis C virus [HCV] ribonucleic acid [RNA; qualitative] is detected);\n\n         13. Serious non-healing wound, ulcer, or bone fracture;\n\n         14. Any severe or uncontrolled medical condition or other condition that could affect\n             participation in the study;\n\n         15. Any current medical, psychiatric, occupational, or substance abuse problems that, in\n             the opinion of the investigator, will make it unlikely that the subject will comply\n             with the protocol.

Patients receiving cytotoxic therapy (including endocrine and biological agents), radiation therapy, immunotherapy or non-topical steroids, within three (3) to four (4) weeks of enrollment.

Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy =< 14 days prior to registration

Non-MF/SS patients who are candidates for topical therapy must be refractory or intolerant to at least 1 prior topical therapy

Patients who have received topical therapy, systemic chemotherapy, or biological therapy within 4 weeks prior to registration are NOT eligible for participation

Patient currently requires systemic therapy.

Prior TCN-PM therapy

Patients must have received one prior line of platinum-based systemic anticancer therapy for advanced or metastatic NSCLC. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued at the end of a treatment regimen.

Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for Bevacizumab).

Prior gene therapy.

Prior hormonal therapy, aromatase inhibitor therapy, and immunotherapy allowed

At least 4 weeks and recovery from effects of prior surgery, hormonal therapy, aromatase inhibitor therapy, immunotherapy, radiotherapy, or other therapy with an approved or investigational agent

Treatment with systemic cancer therapy within 21 days before screening.

Patients who never achieved at least minor response (MR) to at least one prior line of therapy

Prior AQ4N therapy.

Failed conventional therapy for their cancer or have a malignancy for which a conventional therapy does not exist

Therapy related MDS.

Patients must not have received any prior tumor-directed therapy including radiation therapy, chemotherapy (tumor-directed therapy), molecularly targeted agents, or immunotherapy for the treatment of HGG other than surgical intervention

202 Prior anti-cancer therapy as specified below: At least 3 half-lives from first dose of AMG 562 must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc). Other targeted anti-cancer therapy (chemotherapy, antibody therapy,molecular targeted therapy, steroids) within 14 days or 5 half lives (which ever is longer) prior to first dose of AMG 562. Patients requiring continued treatment due to aggressive disease may only be included if there is agreement by both the investigator and the Amgen Medical Monitor. Radiation therapy completed within 28 days prior to first dose of AMG 562. Autologous HSCT within six weeks prior to start of AMG 562 treatment.

Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.

Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy ? 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)\r\n* Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment

Patients taking bisphosphonate therapy for symptomatic hypercalcemia\r\n* Note: use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Participant has received anti-cancer therapy (including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy) prior to Study Day

Patients must have had at least one prior platinum-based chemotherapeutic regimen for management of primary disease; unlimited prior hormonal therapy, targeted therapy or antiangiogenic therapy will be permitted

Any local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ? 4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intra-arterial chemotherapy, without lipiodol or embolizing agents are not eligible.

History of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for metastatic breast cancer (MBC) with the exception of administration of trastuzumab or lapatinib concurrently with radiation therapy for brain metastases; toxicities related to lapatinib should be =< grade 1, per the CTCAE version (v)5.0 and must have been completed at least 2 weeks prior to randomization

Subjects with proven or suspected persistent bacteremia despite 72 hours of both systemic antibiotic therapy and lock therapy to which the infecting organism is susceptible;

Liver tumor-directed therapy, hepatic surgery, antibody-based therapy, or immunotherapy must not have been performed < 28 days, chemotherapy < 21 days, and targeted small molecule therapy or hormonal therapy < 14 days prior to enrollment. No radiation to tumor sites during the last 4 weeks.

Microsatellite instability-high (MSI-H) / mismatch repair-deficient (dMMR) tumors must have received prior therapy with pembrolizumab or nivolumab (where approved in the country) and must have progressed on that therapy.

Previous systemic therapy for stage IV NSCLC, including chemotherapy, radiation therapy or non-cytotoxic investigational agents.

Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria.

Failed at least 1 prior systemic therapy

Have received last dose of first-line systemic anti-cancer therapy or date of most recent local regional therapy >28 days prior to day 1

Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)

Inclusion Criteria:\n\n          -  Histologically confirmed unresectable or metastatic stage IIIB/C/D or IV melanoma\n             using AJCC edition 8\n\n          -  Previously treated for unresectable or metastatic melanoma. Subjects must have at\n             least received the following treatments:\n\n               -  V600BRAF wild-type patients: must have received anti-PD-1/PD-L1 single-agent, or\n                  in combination with anti-CTLA-4 therapy\n\n               -  V600BRAF mutant patients: must have received prior anti-PD-1/PD-L1 single-agent,\n                  or in combination with anti-CTLA-4 therapy. In addition, subjects must have\n                  received prior V600BRAF inhibitor therapy, either single-agent or in combination\n                  with a MEK inhibitor\n\n          -  ECOG performance status 0-2\n\n          -  At least one measurable lesion per RECIST v1.1\n\n          -  At least one lesion, suitable for sequential mandatory tumor biopsies (screening and\n             on-treatment) in accordance with the biopsy guidelines specified in protocol. The same\n             lesion must be biopsied sequentially.\n\n          -  Screening tumor biopsy must fulfill the tissue quality criteria outlined in the\n             protocol, as assessed by a local pathologist\n\n        Key exclusion criteria common to all combination arms:\n\n          -  Subjects with uveal or mucosal melanoma\n\n          -  Presence of clinically active or unstable brain metastasis. Note: Subjects with\n             unstable brain lesions who have been definitively treated with stereotactic radiation\n             therapy, surgery or gamma knife therapy are eligible.\n\n             - Subjects with brain lesions who are untreated (i.e. newly discovered brain lesions\n             during screening) or received whole brain radiation must have documented stable\n             disease as assessed by two consecutive assessments ? 4 weeks apart and have not\n             required steroids for at least ? 4 weeks prior to enrollment.\n\n          -  Use of any live vaccines against infectious diseases within 4 weeks of initiation of\n             study treatment.\n\n          -  Active infection requiring systemic antibiotic therapy.\n\n          -  Systemic chronic steroid therapy (? 10mg/day prednisone or equivalent) or any other\n             immunosuppressive therapy 7 days prior to planned date of first dose of study\n             treatment. Note: Local steroids such as topical, inhaled, nasal and ophthalmic\n             steroids are allowed.\n\n          -  Active, known or suspected autoimmune disease or a documented history of autoimmune\n             disease. Note: Subjects with vitiligo, controlled type I diabetes mellitus on stable\n             insulin dose, residual autoimmune-related hypothyroidism only requiring hormone\n             replacement or psoriasis not requiring systemic treatment are permitted.\n\n          -  Prior allogenic bone marrow or solid organ transplant\n\n          -  History of known hypersensitivity to any of the investigational drugs used in this\n             study

Pathologically-documented diagnosis of multiple myeloma that has relapsed after prior lines of therapy that must include a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and, where approved and available, anti-CD38 therapy in any order OR that is refractory to PI, IMiD, and anti-CD38 therapy. ?Subjects who could not tolerate a PI, IMiDs, or a CD38-directed therapeutic antibody due to unacceptable toxicities are eligible to enroll in the study.

Currently receiving active therapy for other neoplastic disorders

Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given in combination with therapeutic 131I-MIBG.

Currently taking lithium therapy

Prior 131 I-MIBG therapy is excluded

Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy for other reasons [e.g., osteoporosis] is allowed.)

Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigational product) =< 28 days; however, if a therapy has a short half-life, then patients may participate if they received prior treatment =< 28 days from starting study treatment with approval from the principal investigator (PI) and AstraZeneca/Janssen; acceptable washout periods include:\r\n* 3-14 days for prior tyrosine kinase inhibitor (TKI) depending on half-life\r\n* 14-28 days for prior PD-1 or PD-L1 inhibitor treatment depending on the frequency of administration (i.e., wait one full cycle of prior PD-1 axis inhibition before starting study drugs)

Expected requirement for hemodialysis while on study therapy

Requirement for any non-study potentially effective concomitant systemic antibacterial therapy

Prior therapeutic intervention with any of the following:\r\n* Therapeutic anticancer antibodies (rituximab, obinutuzumab) within 4 weeks\r\n* Radio- or toxin-immunoconjugates within 10 weeks\r\n* Inhibitors of PI3K (idelalisib), ibrutinib, BH3-mimetic venetoclax, lenalidomide, and other “targeted” therapy (including investigational BTK inhibitors and other investigational therapy) – within 6 half-lives\r\n* All other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy

Progression on at least two prior lines of therapy for unresectable metastatic colorectal adenocarcinoma\r\n* Administration of bevacizumab previously does not impact study inclusion

History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment

PRE-REGISTRATION: Patients with relapsed or refractory solid tumors and without known curative therapy or therapy proven to proven to prolong survival with acceptable quality of life.

Patients who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose. Mobilization therapy is not considered initial therapy.

Any prior immunotherapy or vaccine therapy

Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 2 weeks prior to initiation of study treatment, with the following exceptions:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week before week 1, day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week before week 1, day 1)

Any skin-directed therapy within 14 days prior to day 1 of protocol therapy

Active infection; any systemic antimicrobial therapy must be completed >= 5 days prior to initiation of protocol therapy

Pathologically confirmed diagnosis of MDS by World Health Organization (WHO) criteria (including secondary and therapy-related disease) who have failed standard therapy, who are intolerant of prior therapy, or who refuse standard therapy; any prior therapy, including ibrutinib and/or lenalidomide (unless intolerant of one or both of these medications), is permitted\r\n* Hypomethylating agent failure is defined as disease progression or stable disease as best response to an adequate course of treatment (at least four cycles) with an injectable hypomethylating agent (azacitidine or decitabine)

No prior docetaxel or cabazitaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) (men treated with prior docetaxel administered as up-front therapy with androgen deprivation therapy [ADT] > 6 months ago will be eligible); prior abiraterone is allowed

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within 28 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C

FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH STANDARD OF CARE (PART 2): The patient condition remains suitable for the selected therapy. If the patient receives prior therapy with a given agent (X) and progressed, but the testing in Part 1 found this agent to be effective in a combination, the patient remains eligible for this combination that includes agent X.

Patients who received most recent therapy =< 4 weeks prior to registration; NOTE: use of systemic steroid therapy is allowed pretreatment

Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest

Subjects must have received at least one line of chemotherapy prior to receiving adoptive T cell therapy and should have exhausted standard of care systemic therapy options; the decision to implement the T cell therapy will be at the discretion of the treating physician; the timing and total exposure to chemotherapy will depend on the tumor type in question (more systemic options for breast cancer; fewer for gastric cancer, for example); due to the heterogeneity of tumors being treated in this protocol, the discretion of the treating physician in terms of timing of immunotherapy will be critical

Patients must not have received chemotherapy within 14 days of enrollment, with the two following exceptions: \r\n* Routine systemic maintenance therapy (e.g., Abelson murine leukemia viral oncogene homolog 1 [ABL] kinase inhibitor, methotrexate, 6-mercaptopurine, vincristine, etc.) and intrathecal/intraventricular therapy\r\n* Systemic therapy for the acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids, cytarabine, etc.)

Prior systemic chemotherapy, molecularly targeted therapy, or radiation therapy for the current OPSCC diagnosis

No prior targeted treatment (tx) or anti-angiogenic therapy; patients may have received one line of prior therapy with octreotide, locoregional therapy; continuation of concurrent octreotide is allowed; patients will be maintained on octreotide (sandostatin) for the duration of their treatment

Any number of prior lines of therapy

Subjects have any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.

No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m^2 per day for one week or less for hyperleukocytosis), and

Use of investigational agents within 30 days or any anticancer therapy for this malignancy within 2 weeks before study entry with the exception of intrathecal (IT) therapy, hydroxyurea, or low-dose cytarabine as stated above; the patient must have recovered from all acute toxicities from any previous therapy

Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week prior to cycle 1, day 1; herbal therapy intended as anticancer therapy must also be discontinued at least 1 week prior to cycle 1, day 1\r\n* Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1

Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Previously untreated with HMAs (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed).

Initiating bisphosphonate or denosumab therapy or adjusting dose/regimen within 3 months prior to Cycle 1 Day 1. Subjects on a stable bisphosphonate or denosumab therapy are eligible and may continue.

Part 1 patients may have an unlimited number of prior therapy regimens

Part 2 patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes [TIL], lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed

Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment

Participants must be at first relapse of GBM; relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy); the intent therefore is that patients had no more than 1 prior therapy (initial treatment); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse

Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors\r\n* Advanced/unresectable is defined by at least 1 of the following criteria: tumors 2 cm or more, tumors considered unresectable, tumors invading deep tissues such as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes and/or distant sites\r\n* Refractory is defined by persistent or recurrent tumor despite prior therapy consisting of at least 1 of the following: surgery, radiation therapy, intralesional therapy, topical therapy, or systemic therapy

Systemic antineoplastic therapy

Prior gene transfer therapy or prior therapy with a cytolytic virus of any type

Previously treated relapsed and refractory multiple myeloma\r\n* Patients must have received at least one prior line of therapy\r\n* Prior therapy must include at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)\r\n* Patients must be refractory and/or relapsed/refractory to lenalidomide or prior lenalidomide\r\n* Disease progression on or within 60 days of completion of last therapy

Prior therapy with elotuzumab

Naïve to prior chemotherapy or immunotherapy (i.e., this is a first-line systemic therapy study).

Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.

Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO Classification

At the time of enrollment, subjects may not have had any prior systemic therapy for breast cancer, including chemotherapy, targeted biologic therapy, or greater than 3 months of hormonal therapy; similarly, chemotherapy or biologic therapy must not be part of the subsequent treatment plan

Subjects with one to three lines of therapy for their disease with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period

Subjects must have completed their most recent drug therapy directed at multiple myeloma in the following timeframes:\r\n* Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy, or investigational agent) at least 21 days prior to cycle 1 day 1 (C1D1) AMG 232 + KRd\r\n* Corticosteroids at least 3 weeks prior to starting AMG-232 + KRd, except for a dose equivalent to dexamethasone of =< 4 mg/day\r\n* Autologous stem cell transplantation at least 12 weeks prior to starting AMG-232 + KRd\r\n* Allogeneic stem cell transplantation at least 24 weeks prior to starting AMG-232 + KRd, and these subjects must also NOT have moderate to severe active acute or chronic graft versus host disease (GVHD)

Subjects with myeloma that is relapsed and/or refractory to KRd when used in combination defined as progression of disease while on therapy or within 60 days of completing therapy

Antineoplastic therapy (e.g. chemotherapy or targeted therapy) for other invasive cancer within 5 years before randomization; (for the purposes of this study, hormonal therapy is not considered chemotherapy)

Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer

Patients must not have received prior radiation therapy (RT), chemotherapy, immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor; corticosteroid therapy is allowed

Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy and intrathecal chemotherapy)

Previous therapy with pazopanib

Any cytotoxic or biologic therapy less than 2 weeks prior to initiation of therapy.

Patients must have prior chemotherapy for advanced CRC and have previously received both an oxaliplatin and an irinotecan based regimen; patients who are not appropriate for second line therapy because of their KRAS gene mutational status or because they cannot tolerate second line therapy, will be included even after only one prior therapy regimen

All prior systemic cancer therapy (hormonal, chemotherapeutic, and immunotherapeutic) must be completed at least 4 weeks before the baseline visit

ARM A: Systemic anti-cancer therapy =< 4 weeks prior to registration

ARM B: Systemic anti-cancer therapy =< 4 weeks prior to registration

Patients must have received < 3 lines of prior therapy and have relapsed less than a year from their last platinum regimen; regimens that are used twice (for example carboplatin and paclitaxel) can be counted as one; if a regimen is changed during the course of treatment due to side effect profile or allergy, the course of therapy is counted as one regimen; (for example, if docetaxel is substituted for paclitaxel due to a reaction during the initial course of adjuvant therapy, this is considered one regimen)

Concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or any other biologic therapy)

DOSE ESCALATION COHORT: Prior treatment with at least one line of systemic therapy

DOSE EXPANSION COHORT: Prior treatment with at least one line of systemic therapy

Prior therapy with axitinib

Intolerance to previous trastuzumab or pertuzumab therapy

Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation therapy, or experimental biological or molecular therapy for at least 4 weeks prior to starting study medication; patients who received FOLFIRINOX must be 6 weeks from the last administration of therapy; patients must have recovered from any acute toxicity related to prior therapy or surgery, to a grade 1 or less unless specified

Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug (=< 28 days prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors [TKIs] [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C); (if sufficient wash-out time has not occurred due to the schedule or pharmacokinetics [PK] properties of an agent, a longer wash-out period may be required)

Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration

Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration

Anti-arrhythmic therapy other than beta blockers or digoxin

No hormonal therapy is allowed within 1 week of initiating study treatment

Concomitant chemotherapy, radiation therapy\r\n* For patients with hyperleukocytosis with > 50,000 blasts/uL; leukapheresis or hydroxyurea may be used prior to study drug administration for cytoreduction at the discretion of the treating physician; hydroxyurea must be stopped 24 hours prior to initiation of protocol defined therapy

Prior radiation is permitted; however, at least 2 weeks must have elapsed since the completion of therapy and patients must have recovered from all therapy-associated toxicities to no greater than grade 1 at the time of registration; patients with symptomatic disease may receive palliative corticosteroids up to 1 week before initiating therapy

Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment

Prior investigational melanoma-directed cancer vaccine therapy

Use of a non-oncology vaccine therapy for prevention of infectious diseases during the 4 week period prior to first dose of NeoVax administration; patients may not receive any non-oncology vaccine therapy during the period of NeoVax administration and until at least 8 weeks after the last dose of study therapy

Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration; NOTE: patients who have recovered from cytopenia related to previous treatment and meet criteria of this protocol will be eligible

Patients may not be receiving any steroids or other anti-immune therapy at the time of registration

Timing of prior therapy:\r\n* Prior hormonal therapy is allowed; hormonal therapy must be discontinued at least 7 days before initiation of protocol therapy\r\n* Ovarian suppression which has been used for > 6 months, during which time there has been disease progression, is allowed concurrently with protocol-based therapy; other hormonal agents (e.g. tamoxifen, aromatase inhibitors, fulvestrant) should be discontinued prior to study entry\r\n* If received, chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry\r\n* Patients must have completed radiation therapy at least 7 days prior to beginning protocol treatment\r\n* Patients must have sufficiently recovered from all reversible toxicities related to prior therapy before beginning protocol treatment, with the exception of alopecia

Participants may or may not be receiving hormonal therapy at the time of study entry

No other experimental therapy is permitted while on study

Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy

Patients must have received at least one prior systemic therapy for lymphoma; a washout period of at least 3 weeks is required from the most recent prior therapy

A minimum of 6 weeks must have elapsed after 131I-MIBG therapy prior to start of protocol therapy

Prior exposure to PLD or anthracycline therapy.

Prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds.

Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy\n             that is considered to be investigational (i.e., used for non-approved indications(s)\n             and in the context of a research investigation). Use of low dose corticosteroid\n             therapy (e.g., for nausea prophylaxis) is acceptable; however, concomitant tamoxifen\n             therapy is not. Supportive care measures are allowed.

Has received previous high dose (>= 600,000 IU/kg) IL-2 therapy; other prior therapy (in the adjuvant or the metastatic setting) is allowed, including immunotherapy, targeted therapy, chemotherapy, or experimental therapy

At least 2 weeks have passed since prior chemotherapy, biological therapy, radiation therapy, major surgery, other investigational or anti-cancer therapy that is considered disease-directed

Patients must have recovered to at least a grade =< 1 toxicity eligibility levels due to adverse events (AEs) and/or toxicity of prior chemotherapy or biologic therapy; they must not have had chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C, or 2 months for UCN-01), or therapy with tyrosine kinase inhibitors within 5 times the half-life of the inhibitors prior to entering the study; patients must be >= 2 weeks since any prior administration of study drug in an exploratory investigational new drug (IND)/phase 0 study; patients must be >= 1 month since completion of any prior radiation (>= 2 weeks for palliative radiation therapy); however, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy\r\n* Prior therapy with topoisomerase I inhibitors is allowed

Be willing to undergo a second core or excisional biopsy of a bone metastasis on therapy (approximately after 8 weeks of study therapy or after 2 doses of radium-223 if delays have occurred)

Has had prior systemic therapy (exception: GnRH agonist or antagonist) or radiation therapy for prostate cancer within 2 weeks prior to study day 1; there must be at least a 2 week washout period from last dose of any prior systemic or radiation therapy for prostate cancer prior to day 1 of study treatment (including nonsteroidal antiandrogens); screening may commence during this washout window

Patients with AML, relapsed or refractory to standard therapy or elderly patients with AML (age 65 or over). Patients who have AML and are younger than age 65 but considered unfit for conventional chemotherapy are eligible. Patients with de novo or treated MDS or chronic myelomonocytic leukemia (CMML) INT-1 or above are eligible. Patients may have had prior exposure to azacitidine but no more than one cycle of decitabine. Patients must have been off chemotherapy for 2 weeks prior to entering this study and have recovered from the toxicities of that therapy; a caveat to this is in the case of rapidly progressive disease. Hydroxyurea is permitted for control of elevated white blood cell (WBC) prior to treatment and can be continued for the first 4 weeks of therapy. Erythropoiesis stimulating agents (ESAs) and granulocyte colony stimulating factor (GCSF) are allowed before therapy. ESAs, GCSF or other growth factors are permitted on therapy.

Not currently receiving any anticancer therapy

Immunosuppressive therapy within 30 days prior to initiation of protocol therapy

Inclusion Criteria:\n\n          1. Patients having histologically confirmed unresectable (Stage III) or metastatic\n             (Stage IV) malignant melanoma with a positive BRAF mutation result determined by\n             Roche CoDx or local CLIA-certified analysis\n\n          2. Patients naïve to a selective BRAF inhibitor therapy or must have progressed after\n             therapy on a selective BRAF inhibitor. For patients entering the protocol progressing\n             on vemurafenib therapy, they must be tolerant of the 960 mg po bid dose.\n\n          3. Tumor biopsies are optional in this study except for patients entering the mandatory\n             biopsy cohorts. Nevertheless tumor biopsies are encouraged, especially in patients\n             with accessible tumors for biopsy to include the collection of formalin-fixed,\n             paraffin-embedded (FFPE) and fresh- frozen tissue (FF) as outlined in the biomarker\n             sections of the protocol. Willingness of patient to give consent of biopsy, should be\n             ascertained\n\n          4. Patients of ? 18 years of age\n\n          5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 or1\n\n          6. Patients with measurable disease per 'Response Evaluation Criteria In Solid Tumors'\n             (RECIST version 1.1)\n\n          7. Patients must have normal organ and adequate marrow function\n\n          8. Patients with ability to swallow and retain oral medication\n\n          9. Women of childbearing potential and men willing to agree to use adequate\n             contraception (hormonal or barrier method of birth control; abstinence) prior to\n             study entry, during the duration of study participation and for at least 4 weeks\n             after withdrawal from the study, unless they are surgically sterilized.\n\n         10. Negative serum pregnancy test within 10 days prior to commencement of therapy dosing\n             in premenopausal women. Women of non-childbearing potential may be included if they\n             are either surgically sterile or have been postmenopausal for ?1 year.\n\n         11. Ability to understand and the willingness to offer a written Informed Consent\n             document prior to the screening procedures for participation into the study\n\n               -  For Extension phase-\n\n               -  For patients entering the protocol progressing on vemurafenib therapy, they must\n                  be tolerant of the vemurafenib dose selected for the extension phase\n\n        Exclusion Criteria:\n\n          1. Prior malignancy (within the last 2 years) except for adequately treated basal cell\n             or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ\n             prostate cancer or any other cancer for which the patient has been disease-free for\n             at least 2 years\n\n          2. Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted\n             anti-cancer therapy (one week  for BRAF inhibitor for melanoma) or surgery within 4\n             weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any\n             radio-or toxin-immunoconjugates) before Day 1 of Investigational product\n             administration and have not recovered (to < Grade 1) from the toxic effects from any\n             prior therapy\n\n          3. Patients having received any other investigational agents within 4 weeks prior to Day\n             1 of Investigational product administration and have not recovered completely (to <\n             Grade 1) from the side effects of the earlier investigational agent\n\n          4. Anticipated administration of any anti-cancer therapies (chemotherapy, radiation\n             therapy, immunotherapy, biological therapy, hormonal therapy, surgery, and/or tumor\n             embolisation) other than those administered in this study such as BRAF inhibitor\n\n          5. Patients with symptomatic or untreated leptomeningeal or brain metastases, or spinal\n             cord compression [patients with previous brain metastases will be allowed to enter\n             the trial if metastases have been surgically removed or all known sites of metastases\n             have been treated with stereotactic high dose radiosurgery. Patients must be off\n             corticosteroids for at least one month and have a stable lesion with verification by\n             imaging (CT/MRI) within 28 days prior to Day 1 of Investigational product\n             administration]\n\n          6. Patients with clinically significant medical condition of malabsorption, inflammatory\n             bowel disease, chronic diarrheal condition, refractory nausea, vomiting or any other\n             condition that will interfere significantly with the absorption of study drugs\n\n          7. Patients with mean QTc interval >480 msec at screening\n\n          8. Treatment with drugs with potential to cause dysrhythmias including but not

Inclusion Criteria:\n\n          1. Patients having histologically confirmed unresectable (Stage III) or metastatic\n             (Stage IV) malignant melanoma with a positive BRAF mutation result determined by\n             Roche CoDx or local CLIA-certified analysis\n\n          2. Patients naïve to a selective BRAF inhibitor therapy or must have progressed after\n             therapy on a selective BRAF inhibitor. For patients entering the protocol progressing\n             on vemurafenib therapy, they must be tolerant of the 960 mg po bid dose.\n\n          3. Tumor biopsies are optional in this study except for patients entering the mandatory\n             biopsy cohorts. Nevertheless tumor biopsies are encouraged, especially in patients\n             with accessible tumors for biopsy to include the collection of formalin-fixed,\n             paraffin-embedded (FFPE) and fresh- frozen tissue (FF) as outlined in the biomarker\n             sections of the protocol. Willingness of patient to give consent of biopsy, should be\n             ascertained\n\n          4. Patients of ? 18 years of age\n\n          5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 or1\n\n          6. Patients with measurable disease per 'Response Evaluation Criteria In Solid Tumors'\n             (RECIST version 1.1)\n\n          7. Patients must have normal organ and adequate marrow function\n\n          8. Patients with ability to swallow and retain oral medication\n\n          9. Women of childbearing potential and men willing to agree to use adequate\n             contraception (hormonal or barrier method of birth control; abstinence) prior to\n             study entry, during the duration of study participation and for at least 4 weeks\n             after withdrawal from the study, unless they are surgically sterilized.\n\n         10. Negative serum pregnancy test within 10 days prior to commencement of therapy dosing\n             in premenopausal women. Women of non-childbearing potential may be included if they\n             are either surgically sterile or have been postmenopausal for ?1 year.\n\n         11. Ability to understand and the willingness to offer a written Informed Consent\n             document prior to the screening procedures for participation into the study\n\n               -  For Extension phase-\n\n               -  For patients entering the protocol progressing on vemurafenib therapy, they must\n                  be tolerant of the vemurafenib dose selected for the extension phase\n\n        Exclusion Criteria:\n\n          1. Prior malignancy (within the last 2 years) except for adequately treated basal cell\n             or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ\n             prostate cancer or any other cancer for which the patient has been disease-free for\n             at least 2 years\n\n          2. Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted\n             anti-cancer therapy (one week  for BRAF inhibitor for melanoma) or surgery within 4\n             weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any\n             radio-or toxin-immunoconjugates) before Day 1 of Investigational product\n             administration and have not recovered (to < Grade 1) from the toxic effects from any\n             prior therapy\n\n          3. Patients having received any other investigational agents within 4 weeks prior to Day\n             1 of Investigational product administration and have not recovered completely (to <\n             Grade 1) from the side effects of the earlier investigational agent\n\n          4. Anticipated administration of any anti-cancer therapies (chemotherapy, radiation\n             therapy, immunotherapy, biological therapy, hormonal therapy, surgery, and/or tumor\n             embolisation) other than those administered in this study such as BRAF inhibitor\n\n          5. Patients with symptomatic or untreated leptomeningeal or brain metastases, or spinal\n             cord compression [patients with previous brain metastases will be allowed to enter\n             the trial if metastases have been surgically removed or all known sites of metastases\n             have been treated with stereotactic high dose radiosurgery. Patients must be off\n             corticosteroids for at least one month and have a stable lesion with verification by\n             imaging (CT/MRI) within 28 days prior to Day 1 of Investigational product\n             administration]\n\n          6. Patients with clinically significant medical condition of malabsorption, inflammatory\n             bowel disease, chronic diarrheal condition, refractory nausea, vomiting or any other\n             condition that will interfere significantly with the absorption of study drugs\n\n          7. Patients with mean QTc interval >480 msec at screening\n\n          8. Treatment with drugs with potential to cause dysrhythmias including but not

Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)

No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least 30 days

Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 7 days should have elapsed from the last day of radiation\r\n* NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate, or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator

Prior therapy requirements:\r\n* At least one prior therapy using an agent with the potential for prolonged remission (generally includes interleukin-2, checkpoint-blocking antibodies, or adoptive cell therapy)\r\n* At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with resolution of the acute toxicities; for patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities; patients must meet entry eligibility criteria\r\n* At least 2 weeks from completion of prior radiation therapy with no residual radiation toxicities\r\n* At least 4 weeks from last dose of prior investigational therapy with recovery to meet baseline eligibility criteria\r\n* Not receiving any current anticancer therapy\r\n* Note: any patient whose tumors carry a B-Raf proto-oncogene, serine/threonine kinase (BRAF) v600 mutation should either be excluded, or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent and agree to forgo Food and Drug Administration (FDA)-approved therapies that increase median survival

Immunosuppressive therapy within 30 days prior to initiation of protocol therapy

Liver-directed therapy (chemoembolization, radioembolization, bland embolization, ablative therapy) within 4 weeks of DEB-TACE

Hepatic encephalopathy refractory to medical therapy

Systemic therapy with sorafenib or other systemic chemotherapeutic agent(s) less than 1 week prior to first planned DEB-TACE

Failed first-line chemotherapy (including systemic and local-regional therapy)

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment regorafenib; however, the palliative radiation therapy (XRT) to non-targeted lesions is allowed

Subjects must not have had prior pazopanib therapy

Up to 3 lines of prior vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) targeted therapy are permitted; any prior therapy should have been completed >= 2 weeks prior to start of study therapy

Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)

Bisphosphonate therapy for symptomatic hypercalcemia\r\n* Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, low dose cytarabine, and intrathecal chemotherapy which is permitted up to 24 hours prior to the start of protocol therapy; for patients with aggressive disease that is in the peripheral blood and rising, this 14 day washout period may be omitted

Subjects should be > 2 weeks from prior systemic chemotherapy for breast cancer AND should have recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy prior to study entry; NOTE: For subjects who are, or who have previously received endocrine therapy for breast cancer, the treating investigator will decide how many days should pass between the last dose of endocrine therapy and the first dose of study treatment

Subjects desire focal therapy and decline conventional treatment (active surveillance, radical prostatectomy, radiation therapy, cryosurgery and hormone therapy)

Any prior treatment for prostate cancer \r\n* Radical prostatectomy \r\n* Radiation therapy (external beam or brachytherapy) \r\n* Cryotherapy \r\n* High intensity focused ultrasound treatment \r\n* Photodynamic therapy \r\n* Androgen deprivation therapy

AML has relapsed after, or is refractory to, first-line therapy, with or without additional subsequent therapy

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Other ongoing systemic therapy for cancer, including any other experimental treatment; these include concomitant therapy with any of the following: interleukin (IL)-2, interferon, ipilimumab or other immunotherapy; cytotoxic chemotherapy; and targeted therapies

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

For stage 1 (all patients) and dose expansion (stage 2) endometrial and ovarian cancer cohorts, participants are allowed following unlimited prior therapy; for stage 2 GBM participants, no more than 2 prior relapses are allowed; for these patients, relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy) or a subsequent therapy; the intent therefore is that GBM patients enrolling onto stage 2 had no more than 3 prior therapies (initial and treatment for 2 relapses); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse\r\n* NOTE: for participants who had prior therapy for a low-grade glioma, the surgical diagnosis of glioblastoma will be considered the first relapse; therefore, these participants may have had more than 3 prior therapies

Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting; trastuzumab emtansine (T-DM1) would count as a line of therapy and patients previously treated with T-DM1 are eligible

Therapeutic options: patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Previous treatment with genetically engineered GD2-CAR T cells; previous vaccine therapy, anti-GD2 mAb therapy or therapy with other genetically engineered T cells is not an exclusion criteria

Patient may have had any prior topical or systemic therapy except for total electron beam irradiation; patients must be a minimum of 2 weeks from topical therapy and 3 weeks from systemic therapies, phototherapy, or local radiation therapy before initiating protocol specific therapy except for HDACI if they are in Arm B; patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month

Patient has had prior therapy with neural stem cells

Treatment including radiation therapy (RT), chemotherapy, targeted therapy, or endocrine therapy for the currently diagnosed breast cancer prior to randomization

Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (these patients are eligible if this therapy is discontinued prior to randomization)

Not currently receiving therapy

No recent treatment for thyroid cancer as defined as:\r\n* No radioactive iodine therapy is allowed if given < 3 months prior to initiation of this protocol therapy; a diagnostic study using < 10 mCi of radioactive iodine (RAI) is not considered radioactive iodine therapy\r\n* No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol\r\n* No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy

Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment

Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment

Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

Relapsed or refractory after at least 1 front-line therapy

No concomitant anti-cancer therapy unless specified above

Patients may have received any number of prior systemic treatment regimens for distant metastatic disease or advanced regional disease; the following prior therapy is permitted in either the adjuvant or metastatic disease setting:\r\n* No prior therapy\r\n* Immunotherapy consisting of interferon-alpha, interleukin-2, GM-CSF, ipilimumab, anti-PD1, cancer vaccines, or other experimental agent\r\n* Cytotoxic chemotherapy consisting of dacarbazine, temozolomide, carboplatin, or paclitaxel alone or in combination\r\n* Targeted therapy with temsirolimus, bevacizumab, or sorafenib

Patients who have had any prior therapy for pancreatic cancer

Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)

Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Received at least one prior treatment with standard therapy (previous antibody\n             therapy is acceptable)

Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy

Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, biological therapy and hormonal therapy) while taking study medication

ENTRY CRITERIA:\n\n        DISEASE CHARATERISTICS:\n\n          -  Muscle invasive or metastatic urothelial cancer of bladder, ureters, renal pelvis,\n             and urethra\n\n          -  Histologically or cytologically confirmed with a clinical plan that would potentially\n             include cisplatin* plus gemcitabine systemic therapy or with disease refractory to a\n             first-line platinum-based therapy (as defined in the protocol).\n\n             * Does not apply to patients screened for Phase II expansion\n\n          -  Surgically incurable\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No concurrent radiotherapy, other chemotherapy, or other immunotherapy\n\n          -  Must have recovered from side effects of prior treatments\n\n          -  If prior Proleukin® treatment, must have had a clinical benefit\n\n          -  No use of other investigational agents within 30 days of start or concurrently\n\n        PATIENT CHARACTERISTICS:\n\n        Age\n\n          -  ? 18 years\n\n        Performance Status\n\n          -  ECOG 0 or 1\n\n        Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1,500/uL\n\n          -  Platelets ? 100,000/uL\n\n          -  Hemoglobin ? 10g/dL\n\n        Renal Function\n\n          -  Glomerular Filtration Rate (GFR):\n\n               -  ? 50mL/min/1.73m^2 for cisplatin-containing regimen\n\n               -  ? 40mL/min/1.73m^2 for non-cisplatin-containing regimen\n\n        Hepatic Function\n\n          -  Total bilirubin ? 1.5 X ULN\n\n          -  AST, ALT, ALP ? 2.5 X ULN, or ? 5.0 X ULN (if liver metastases exists)\n\n          -  PT INR ? 1.5 X ULN\n\n        Cardiovascular\n\n          -  No congestive heart failure < 6 months\n\n          -  No unstable angina pectoris < 6 months\n\n          -  No myocardial infarction < 6 months\n\n          -  No history of ventricular arrhythmias\n\n          -  No NYHA Class > II CHF\n\n          -  Normal cardiac stress test required for subjects who are ? 50 years old, or have a\n             history of EKG abnormalities, or have symptoms of cardiac ischemia or arrhythmia\n\n          -  No uncontrolled hypertension\n\n        Pulmonary\n\n          -  Not receiving chronic medication for asthma\n\n          -  Normal clinical assessment of pulmonary function\n\n        Hematologic\n\n          -  No evidence of bleeding diathesis or coagulopathy\n\n        Other\n\n          -  Negative serum pregnancy test if female and of childbearing potential\n\n          -  No women who are pregnant or nursing\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No known autoimmune disease other than corrected hypothyroidism\n\n          -  No known prior organ allograft or allogeneic transplantation\n\n          -  Not HIV positive\n\n          -  No active systemic infection requiring parenteral antibiotic therapy\n\n          -  No ongoing systemic steroid therapy required\n\n          -  No history or evidence of CNS disease (Controlled brain metastases treated with\n             radiation therapy or surgery where the disease has been clinically stable for a\n             period of a least 3 months before screening is allowed)\n\n          -  No psychiatric illness/social situation\n\n          -  No other illness that in the opinion of the investigator would exclude the subject\n             from participating in the study\n\n          -  Must provide informed consent and HIPAA authorization and agree to comply with all\n             protocol-specified procedures and follow-up evaluations

ENTRY CRITERIA:\n\n        DISEASE CHARATERISTICS:\n\n          -  Muscle invasive or metastatic urothelial cancer of bladder, ureters, renal pelvis,\n             and urethra\n\n          -  Histologically or cytologically confirmed with a clinical plan that would potentially\n             include cisplatin* plus gemcitabine systemic therapy or with disease refractory to a\n             first-line platinum-based therapy (as defined in the protocol).\n\n             * Does not apply to patients screened for Phase II expansion\n\n          -  Surgically incurable\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No concurrent radiotherapy, other chemotherapy, or other immunotherapy\n\n          -  Must have recovered from side effects of prior treatments\n\n          -  If prior Proleukin® treatment, must have had a clinical benefit\n\n          -  No use of other investigational agents within 30 days of start or concurrently\n\n        PATIENT CHARACTERISTICS:\n\n        Age\n\n          -  ? 18 years\n\n        Performance Status\n\n          -  ECOG 0 or 1\n\n        Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1,500/uL\n\n          -  Platelets ? 100,000/uL\n\n          -  Hemoglobin ? 10g/dL\n\n        Renal Function\n\n          -  Glomerular Filtration Rate (GFR):\n\n               -  ? 50mL/min/1.73m^2 for cisplatin-containing regimen\n\n               -  ? 40mL/min/1.73m^2 for non-cisplatin-containing regimen\n\n        Hepatic Function\n\n          -  Total bilirubin ? 1.5 X ULN\n\n          -  AST, ALT, ALP ? 2.5 X ULN, or ? 5.0 X ULN (if liver metastases exists)\n\n          -  PT INR ? 1.5 X ULN\n\n        Cardiovascular\n\n          -  No congestive heart failure < 6 months\n\n          -  No unstable angina pectoris < 6 months\n\n          -  No myocardial infarction < 6 months\n\n          -  No history of ventricular arrhythmias\n\n          -  No NYHA Class > II CHF\n\n          -  Normal cardiac stress test required for subjects who are ? 50 years old, or have a\n             history of EKG abnormalities, or have symptoms of cardiac ischemia or arrhythmia\n\n          -  No uncontrolled hypertension\n\n        Pulmonary\n\n          -  Not receiving chronic medication for asthma\n\n          -  Normal clinical assessment of pulmonary function\n\n        Hematologic\n\n          -  No evidence of bleeding diathesis or coagulopathy\n\n        Other\n\n          -  Negative serum pregnancy test if female and of childbearing potential\n\n          -  No women who are pregnant or nursing\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No known autoimmune disease other than corrected hypothyroidism\n\n          -  No known prior organ allograft or allogeneic transplantation\n\n          -  Not HIV positive\n\n          -  No active systemic infection requiring parenteral antibiotic therapy\n\n          -  No ongoing systemic steroid therapy required\n\n          -  No history or evidence of CNS disease (Controlled brain metastases treated with\n             radiation therapy or surgery where the disease has been clinically stable for a\n             period of a least 3 months before screening is allowed)\n\n          -  No psychiatric illness/social situation\n\n          -  No other illness that in the opinion of the investigator would exclude the subject\n             from participating in the study\n\n          -  Must provide informed consent and HIPAA authorization and agree to comply with all\n             protocol-specified procedures and follow-up evaluations

All previous immunologic or molecularly targeted therapy must be completed at least 2 weeks prior to study entry; any prior non-hematologic toxicity of any previous therapy must have resolved to grade 1 or less, unless specified elsewhere, or except breakpoint cluster region/tyrosine-protein kinase ABL1 (BCR-ABL) tyrosine kinase in patients who have Philadelphia chromosome positive (Ph+) ALL, where there will be no washout period

Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to day 1 if the patient has recovered from all adverse events (AEs) to grade 1 except for alopecia

Prior therapy with trastuzumab

Patients must not have received any prior systemic therapy (chemotherapy or other biologic therapy) for their unresectable malignant pleural mesothelioma; prior systemic chemotherapy or biologic therapy is allowed as neoadjuvant or adjuvant treatment, disease has now recurred, and all systemic treatment was completed > 6 months prior registration; prior therapy must not have included cediranib

Prior resection permitted, no prior systemic, ablative or infusion therapy permitted

Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy:\r\n* Myelosuppressive chemotherapy:\r\n** Solid tumors: Patients with solid tumors must not have received chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)\r\n** Lymphoma: Patients with lymphoma who relapse during standard maintenance therapy are eligible at time of relapse; for patients with ALCL who relapse while they are receiving cytotoxic therapy, at least 14 days must have elapsed since the completion of cytotoxic therapy; Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of PF-02341066

Prior therapy with LMB-2

Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)

Neoadjuvant hormonal therapy prior to radical prostatectomy is allowed, and post-prostatectomy hormonal therapy is allowed only if the onset of androgen ablation is =< 90 days prior to the date of registration

Participant treated with any prior systemic therapy for myeloma; treatment by localized radiotherapy is not an exclusion criterion if an interval of at least 7 days between the end of radiotherapy and initiation of protocol therapy is observed; intervals of less than 7 days between radiotherapy and initiation of protocol therapy will be considered on a case by case basis with the lead principal investigator (PI), provided toxicity is not a concern; similarly, the dose of corticosteroids received by the participant as part of initial therapy for myeloma should not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol therapy

Refractory to first-line AML therapy is defined as:

Patient has not received prior anti-angiogenic therapy, systemic targeted agents or systemic chemotherapy\r\n* Prior surgical resection, chemoembolization or other local therapy prior to transplant is permitted

Has completed a prior therapy (ies) according to the criteria below:

Allowable prior therapy:

Brain lesion size > 3cm 3. Medical History and Concurrent Diseases a) History of whole brain irradiation b) Subjects with an active, known or suspected autoimmune disease c) Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled d) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. For any prior invasive malignancy, at least 5 years must have elapsed since curative therapy and patients must have no residual sequelae of prior therapy e) Cohort A (asymptomatic): The use of corticosteroids is not allowed within 10 days prior to first treatment (based upon 5 times the expected half life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the sponsor Medical Monitor is required to determine the washout period prior to initiating study treatment Cohort B (symptomatic): Subjects with neurologic sign and symptoms related to brain metastases who are being treated with a total daily dose of higher than 4 mg dexamethasone or equivalent within 10 prior to the start of treatment with study drug are excluded.

Prior Therapy Criteria:

Patient must have no plans to receive any other experimental therapy while on the protocol treatment; previous experimental therapy must have been completed at least 28 days prior to registration

Prior/Concomitant Therapy

The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment. However, subjects with low-risk prostate cancer, e.g.:

Previous first line therapy with at least radiotherapy and temozolomide.

Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa-? ligand inhibitor) must be on stable doses for ?4 weeks prior to first dose of study therapy

For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)

Prior therapy:\r\n* No limit to prior therapies with last anti-cancer treatment >= 2 weeks from initiation of protocol-based therapy provided all toxicities (other than alopecia) have resolved to =< grade 1 or baseline; for lapatinib and intravenous (IV) trastuzumab and/or pertuzumab, no washout is required\r\n* Patients with prior whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) are eligible, provided that there are new lesions not previously treated by SRS and >= 4 weeks have passed since radiation\r\n* Patients with prior cranial surgery are eligible, provided that there is evidence of residual disease and/or progression of disease and >= 4 weeks have passed since surgery\r\n* Prior hormonal therapy for locally advanced or metastatic disease is allowed and can be continued, if everolimus is used in a combination with hormonal therapy, then, everolimus must be discontinued but hormonal therapy can be continued\r\n* Continuation of intravenous (IV) trastuzumab is allowed for those patients already on IV trastuzumab therapy, patients previously treated with intrathecal (IT) trastuzumab are allowed if there is evidence of progression as determined by treating physician and last dose administered is >= 4 weeks\r\n* Prior capecitabine therapy is allowed, provided >= 6 months have passed since the last dose of capecitabine

Concurrent anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, tumor embolization, or biologic therapy including pertuzumab, but except IV trastuzumab or hormonal therapy, if patient is already being treated with either of the two agents)

Prior systemic therapy requirements.

Prior taxane therapy for metastatic breast cancer is allowed if the patient received ? 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to C1D-2.

They have had previous I-131 MIBG therapy

Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days before randomization

Part 1: Progression of disease following up to three lines of prior therapy, including at least one approved VEGF receptor tyrosine kinase inhibitor for RCC. Adjuvant therapy is permitted as one line of prior therapy.

A minimum of 1 week since the last dose of prior therapy (a minimum of 4 weeks since anticancer immune therapy or bevacizumab +/- interferon).

Use of protocol-defined prior/concomitant therapy.

Prior therapy with any antibody or drug targeting T-cell coregulatory proteins

Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after step 2 registration

Treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy

There is no upper limit on prior chemotherapy, targeted therapy, or endocrine therapy

Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose.

Prior radio- or toxin-conjugated antibody therapy.

Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy

Subject has received zero to one prior cytotoxic chemotherapy regimen for metastatic disease, regardless of prior targeted therapy (eg. everolimus, palbociclib or lapatinib), biologic (eg. trastuzumab) or hormonal therapy treatment (eg. aromatase inhibitors, selective estrogen receptor modulators, or estrogen receptor down-regulators).

No prior therapy for AML, except for hydroxyurea, in this setting is allowed.

Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy

Prior intra-arterial liver directed therapy, including transcatheter arterial chemoembolization (TACE) or Y-90 microsphere therapy

Concurrent administration of any other anti-cancer therapy within 14 days of starting protocol therapy and during the course of this study (bisphosphonates and RANK ligand inhibitors are allowed)

Patients with no more than 2 prior treatments with systemic anti-neoplastic therapy for CCA.

Prior immune-oncology therapy

Prior treatment with an immune-therapy.

Prior therapy\r\n* Patients must have recurred or progressed following at least one platinum-based chemotherapy regimen\r\n* Patients may have received an unlimited number of prior therapy regimens\r\n* Patients may not have received all of the five choices in the “standard therapy” arm\r\n* Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration\r\n* Any other prior therapy directed at the malignant tumor, including chemotherapy and radiation therapy, must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 28 days prior to registration

Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy

Time elapsed from previous therapy must be ? 3 weeks for systemic therapy, ? 2 weeks for radiation therapy or major surgery.

Prior therapy criteria must be met

Patients must not have received any prior systemic therapy (chemotherapy or other biologic therapy) for lung cancer

Patients must not have received any prior anti-cancer therapy (except for radical or partial nephrectomy noted above) for renal cell carcinoma, including systemic therapy in the adjuvant or neoadjuvant setting, immunotherapy, investigational therapy, surgical metastasectomy, or radiation therapy

Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to treatment allocation.

have had documented radiographic or symptomatic progression during or after sorafenib therapy; OR

Completion of all prior anticancer therapy before first ACP-196 dose.

Three or more prior lines of systemic therapy for GBM.

Unresolved toxicities from prior anticancer therapy

Is expected to require any other form of antineoplastic therapy while on study.

Patients must not have received prior surgery, radiation therapy, chemotherapy, targeted therapy, or any investigational therapy for pancreatic cancer

Inclusion Criteria:\n\n        Subjects must meet all of the following criteria to be eligible for the study:\n\n          1. Phase 1a portion: Histologically confirmed advanced relapsed or refractory solid\n             tumors that have exhausted standard of care therapy or either refuse or are not\n             considered to be candidates for any remaining standard therapy.\n\n          2. Age ?18 years\n\n          3. ECOG performance status 0 or 1 (see Appendix B)\n\n          4. Must have evaluable disease per RECIST 1.1. (see Appendix C)\n\n          5. Subjects must have Formalin-Fixed, Paraffin-Embedded (FFPE) tissue available either\n             archived or fresh core or punch needle biopsied at study entry (two fresh\n             cores/punches preferred whenever possible).\n\n          6. Must have received their last anti-cancer therapy, including radiotherapy,\n             chemotherapy, biologic therapy, or herbal therapy at least 3 weeks or 5 half-lives\n             (for systemic agents), whichever is shorter, from initiation of study treatment.\n\n          7. Platelets >100,000/mL without transfusions in the past 7 days\n\n          8. Total bilirubin within 1.5x institutional upper limit of normal (ULN)\n\n               -  AST (SGOT) and ALT (SGPT) <3 X institutional ULN\n\n               -  Patients with documented liver metastases: AST (SGOT) and/or ALT (SGPT) ? 5 × ULN\n\n               -  Albumin ? 3.0 g/dL\n\n               -  Creatinine <1.5 X institutional ULN OR\n\n               -  Creatinine clearance >50 mL/min/1.73 m2 for subjects with creatinine levels above\n                  institutional normal\n\n        Exclusion Criteria:\n\n        Subjects who meet any of the following criteria will not be eligible for participation in\n        the study:\n\n          1. Currently receiving any therapeutic treatment for their malignancy including other\n             investigational agents\n\n          2. Uncontrolled seizure disorder, active neurologic disease, or active CNS involvement\n             except for individuals who have previously treated CNS metastases, are asymptomatic,\n             and have no requirement for a corticosteroid dose (indicated to reduce brain edema)\n             that is equivalent to a prednisone dose of >10mg orally per day or anti-seizure\n             medication for at least 4 weeks prior to first dose of study drug.\n\n          3. History of a Grade 3 or 4 allergic reaction attributed to humanized or human\n             monoclonal antibody therapy\n\n          4. Significant intercurrent illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac\n             arrhythmia, or psychiatric illness/social situations that would limit compliance with\n             study requirements\n\n          5. Pregnant women or nursing women\n\n          6. Subjects with congestive heart failure with New York Heart Association Classification\n             III, or IV (see Appendix D)\n\n          7. Known clinically significant gastrointestinal disease including, but not limited to,\n             inflammatory bowel disease

Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy

Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment

Completion of all therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ? 4 weeks before the start of study therapy.

Comorbidity that would interfere with therapy

There is no limitation in the number of prior lines of therapy

Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.

Previous therapy with:

Chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 2 weeks (or five elimination half lives for noncytotoxics, whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin). Subjects on therapy with trastuzumab (trastuzumab cohort) may continue with trastuzumab during the screening phase of the study. Subjects on endocrine therapy may continue with antihormonal therapy until Day 1 of the study.

Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)

Would receive study treatment within 3 weeks from radiation therapy, experimental therapy, hormonal therapy, prior chemotherapy, or biological therapy; use an invasive investigational device; or is currently enrolled in an investigational study

Prior systemic chemotherapy or anti-EGF therapy for the study cancer; note: prior chemotherapy or anti-EGF therapy for a different cancer is allowable

If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.

Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of day 1 and no evidence of disease progression during or after the completion of docetaxel therapy;

Planned treatment with other experimental drugs or any other non-hormonal anti-cancer therapy;

Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days prior to study day 1

Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent

Subject is expected to require any other form of systemic or localized antineoplastic therapy while on study

Use of hormonal therapy or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) or use of an investigational agent within 4 weeks of randomization;

At least 2 weeks since prior chemotherapy, biological therapy, radiation therapy, major surgery, other investigational, or anti-cancer therapy that is considered disease-directed and recovered from prior toxicities to grade 0-1 at least 2 weeks prior to investigational therapy

Patients must not have prior therapy with lenalidomide

Patients must be registered to Consolidation therapy within 60 days of beginning Induction therapy (with day 1 being the start of Induction)

Recovery from the effects of previous chemotherapy, with a minimum of 21 days from initiation of last therapy; hydroxyurea or anagrelide may be used to manage elevated cell counts in patients up to the time they begin therapy under this protocol

Treatment-naïve participants (no prior systemic anticancer therapy for unresectable or metastatic melanoma)

Prior therapy(ies), if applicable, must be completed according to the criteria below prior to first dose of tazemetostat:

Prior therapy containing MMAE

Any concomitant systemic therapy or radiation therapy initiated for this malignancy.

Patients taking herbal remedies (e.g., St. John's Wort [Hypericum perforatum]) who cannot interrupt therapy from the time the C-13 consent is signed through 30 days after the last dose of study therapy.

No prior exposure to immune-mediated therapy,

Inclusion Criteria:\n\n        A subject must satisfy all of the following criteria to be considered for inclusion in the\n        study:\n\n          -  Subjects with histologically or cytologically-confirmed diagnosis of cancer that is\n             recurrent, metastatic, or persistent, who have relapsed from or are refractory to\n             treatment and who also meet the following corresponding requirements for the cohort or\n             phase of the study into which they will enroll:\n\n               -  Dose-escalation Phase: Subjects with advanced solid tumors (any tumor type)\n                  considered to have no standard-of-care treatment for their malignancy with a\n                  curative intent, either as initial therapy or after progressing to prior\n                  therapies; subjects who have been treated previously with a CSF1R inhibitor or an\n                  anti PD1/PDL1 inhibitor may enroll.\n\n               -  Expansion Phase: Subjects with advanced melanoma, non-small-cell lung cancer\n                  (non-squamous; EGFR, ALK wild type), squamous cell carcinoma of the head and\n                  neck, ovarian cancer, or gastrointestinal stromal tumor.\n\n          -  Subjects with melanoma must have a histologically confirmed diagnosis of stage III\n             disease not amenable to local therapy. Melanoma subjects may have received any number\n             of prior lines of therapy for metastatic disease and must have measurable disease per\n             RECISTv1.1. Subjects with melanoma who have received prior treatment with a BRAF/MEK\n             inhibitor are acceptable candidates.\n\n          -  Expansion cohorts: Subjects must have relapsed or been refractory to standard\n             treatment. NSCLC, SCCHN, and Melanoma must show primary progression with\n             antiPD1/anti-PDL1 therapy. They must have tumor accessible for sequential biopsy (core\n             needle biopsy or excision required) and be willing to provide on study tumor tissue\n             biopsy. Subjects for whom newly obtained samples cannot be obtained (e.g. inaccessible\n             or patient safety concern) may submit an archived specimen only upon agreement from\n             the Sponsor.\n\n          -  ECOG performance status 0 or 1.\n\n          -  Adequate organ function as demonstrated by laboratory values.\n\n        Exclusion Criteria:\n\n        A subject who meets any of the following criteria will be disqualified from entering the\n        study:\n\n          -  Disease that is suitable for local therapy administered with curative intent.\n\n          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other\n             form of immunosuppressive therapy within 7 days prior to the first dose of study\n             treatment.\n\n          -  Is currently participating and receiving study therapy or has participated in a study\n             of an investigational agent and received study therapy or used an investigational\n             device within 28 days prior to the first dose of study treatment.\n\n          -  Has had monoclonal antibody within 28 days of first dose of study treatment or has not\n             recovered from AEs due to agents administered more than 28 days earlier.\n\n          -  Has had chemotherapy, targeted small molecule therapy, or radiation therapy within 14\n             days prior to first dose of study treatment or who has not recovered from AEs due to a\n             previously administered agent.\n\n               -  Note: Subjects with ? Grade 2 neuropathy or ? Grade 2 alopecia are an exception\n                  to this criterion and may qualify for the study.\n\n               -  Note: If a subject received major surgery, he or she must have recovered\n                  adequately from the toxicity and/or complications from the intervention prior to\n                  starting study treatment.\n\n          -  Has received transfusion of blood products (including platelets or red blood cells\n             [RBC]) or administration of colony stimulating factors (including granulocyte\n             colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or\n             recombinant erythropoietin) within 28 days prior to Day 1.\n\n          -  Evidence of interstitial lung disease or active, noninfectious pneumonitis.\n\n          -  Has a known additional malignancy that is progressing or requires active treatment.\n             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the\n             skin that has undergone potentially curative therapy, in situ cervical cancer and\n             isolated elevation of prostate-specific antigen. Subjects with a completely treated\n             prior malignancy with no evidence of disease for ? 2 years are eligible.\n\n          -  For Expansion cohort subjects who have previously received an anti-PD-1, anti-PD-L1,\n             or anti?PD-L2 agent or has previously participated in pembrolizumab clinical trials\n             are excluded, except the following tumor types Melanoma, NSCLC and SCCHN (who must\n             show primary progression to anti-PD1/anti-PDL1 therapy).\n\n          -  Radiation therapy within 14 days of first dose of study treatment.\n\n          -  Has active autoimmune disease that has required systemic treatment in past 2 years\n             (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive\n             drugs). Replacement therapy is not considered a form of systemic treatment.\n\n          -  Has an active infection requiring systemic therapy.\n\n          -  Has known central nervous system metastases and/or carcinomatous meningitis.\n\n             o Note: Subjects with previously treated brain metastases may participate if they meet\n             the following criteria: 1) are stable for at least 28 days prior to the first dose of\n             study treatment and if all neurologic symptoms returned to baseline); 2) have no\n             evidence of new or enlarging brain metastases; and 3) have not been using steroids for\n             at least 7 days prior to first dose of study treatment. This exception does not\n             include carcinomatous meningitis, which is excluded regardless of clinical stability.\n\n          -  Uncontrolled intercurrent illness.\n\n          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant\n             small bowel resection that would preclude adequate absorption.\n\n          -  QT interval corrected using Fridericia's formula (QTc) ? 450 msec (males) or ? 470\n             msec (females) at Screening.\n\n          -  Congenital long QT syndrome or patients taking concomitant medications known to\n             prolong the QT interval.\n\n          -  Major surgery within 28 days prior to first dose of study treatment.\n\n          -  Has received a live vaccine administered within 30 days prior to first dose of study\n             treatment.\n\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\n             that might confound the results of the trial, interfere with the subject's\n             participation for the full duration of the trial, or is not in the best interest of\n             the subject to participate, in the opinion of the treating investigator.\n\n          -  Active and clinically significant bacterial, fungal or viral infection, including\n             hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus\n             (HIV) or acquired immunodeficiency syndrome related illness (HIV testing is not\n             required), including subjects who have an active infection requiring systemic therapy.\n\n          -  Any of the following within 48 weeks (~1 year) prior to first dose of study treatment:\n             myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,\n             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic\n             attack.\n\n          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the\n             projected duration of the trial, starting with the screening visit through 120 days\n             after the last dose of study treatment.\n\n          -  Has known psychiatric or substance abuse disorders that would interfere with\n             cooperation with the requirements of the trial.\n\n          -  Has had prior exposure to PLX3397.

Inclusion Criteria:\n\n        For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not\n        count as a prior line of therapy.\n\n        For Cohorts A and C:\n\n          -  At least one systemic treatment for metastatic breast cancer\n\n          -  Documented disease progression on or after the most recent therapy\n\n          -  Prior treatment must include an anthracycline and a taxane in the neoadjuvant,\n             adjuvant, or metastatic setting\n\n        For Cohort B:\n\n          -  No prior systemic treatment for metastatic breast cancer\n\n          -  Programmed cell death-ligand 1 (PD-L1)-positive mTNBC.\n\n        For Cohort C:\n\n        - PD-L1 strong positive mTNBC\n\n        For all cohorts:\n\n          -  mTNBC confirmed by a central laboratory\n\n          -  For biomarker analysis, adequate newly obtained core or excisional biopsy of a\n             not-previously-irradiated metastatic tumor lesion (mandatory)\n\n          -  Measurable metastatic disease\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n\n          -  Female participants of childbearing potential should be willing to use 2 methods of\n             birth control or be surgically sterile, or abstain from heterosexual activity for the\n             course of the study through 120 days after the last dose of study treatment\n\n          -  Male participants should agree to use an adequate method of contraception starting\n             with the first dose of study treatment through 120 days after the last dose of study\n             treatment\n\n          -  Adequate organ function\n\n        Exclusion Criteria:\n\n          -  Currently participating and receiving study treatment, or has participated in a study\n             of an investigational agent and received study therapy or used an investigational\n             device within 4 weeks prior to study Day 1\n\n          -  Prior anti-cancer monoclonal antibody (mAb) therapy for direct anti-neoplastic\n             treatment within 4 weeks prior to study Day 1\n\n          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within at\n             least 2 weeks prior to study Day 1\n\n          -  Not recovered (i.e., ? Grade 1 or at baseline) from adverse events due to agents\n             administered within at least 2 weeks prior to study Day 1\n\n          -  Active autoimmune disease requiring systemic treatment in past 2 years\n\n          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form\n             of immunosuppressive therapy within 7 days prior to the first dose of study treatment\n\n          -  Known additional malignancy that progressed or required active treatment within the\n             last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell\n             carcinoma of the skin that has undergone potentially curative therapy, or in situ\n             cervical cancer\n\n          -  Radiographically-detectable central nervous system (CNS) metastases and/or\n             carcinomatous meningitis\n\n          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis\n             or a history of interstitial lung disease\n\n          -  Active infection requiring systemic therapy\n\n          -  Known psychiatric or substance abuse disorders that would interfere with cooperation\n             with the requirements of the study\n\n          -  Pregnant, breastfeeding, or expecting to conceive or father children within the\n             projected duration of the study, starting with the screening visit through 120 days\n             after the last dose of study treatment\n\n          -  Prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1,\n             anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor\n             (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137) or has\n             participated in Merck MK-3475 (pembrolizumab) study\n\n          -  Known history of human immunodeficiency virus (HIV)\n\n          -  Known active Hepatitis B or C\n\n          -  Received a live vaccine within 30 days of planned start of study treatment

received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy

not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy

Inclusion Criteria: - Age ?18 years; - Written informed consent obtained from the\n        patient/legal representative; - Histologically or cytologically confirmed recurrent or\n        metastatic SCCHN; - Tumor progression or recurrence during or after only one palliative\n        systemic treatment regimen for recurrent or metastatic disease that must have contained a\n        platinum agent OR progression within 6 months of the last dose of platinum given as part of\n        multimodality therapy with curative intent; - Confirmed PD-L1-positive or -negative SCCHN\n        by the Ventana PD-L1 SP263 IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG)\n        performance status of 0 or 1; At least 1 measurable lesion, - Not previously irradiated; -\n        No prior exposure to immune-mediated therapy; - Adequate organ and marrow function;\n        Evidence of post-menopausal status or negative urinary or serum pregnancy test for female\n        pre-menopausal patients. Exclusion Criteria: - Histologically or cytologically confirmed\n        squamous cell carcinoma of any other primary anatomic location in the head and neck; -\n        Received more than 1 palliative systemic regimen for recurrent or metastatic disease; -Any\n        concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer\n        treatment; - Receipt of any investigational anticancer therapy within 28 days or 5\n        half-lives; - Receipt of last dose of an approved (marketed) anticancer therapy\n        (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the\n        first dose of study treatment; - Major surgical procedure within 28 days prior to the first\n        dose of Investigational Product; - Any unresolved toxicity NCI CTCAE Grade ?2 from previous\n        anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values\n        defined in the inclusion criterion; - Current or prior use of immunosuppressive medication\n        within 14 days before the first dose of their assigned Investigational Product; - History\n        of allogeneic organ transplantation; - Active or prior documented autoimmune or\n        inflammatory disorders; - Uncontrolled intercurrent illness; - Patients with a history of\n        brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - Mean QT\n        interval corrected for heart rate (QTc) ?470 ms calculated from 3 electrocardiograms (ECGs)\n        using Fridericia's Correction; - History of active primary immunodeficiency; - Active\n        tuberculosis; - Active infection including hepatitis B, hepatitis C or human\n        immunodeficiency virus (HIV); - Receipt of live, attenuated vaccine within 30 days prior to\n        the first dose of Investigational Product; - Pregnant or breast-feeding female patients; -\n        Known allergy or hypersensitivity to Investigational Product

All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy has shown an increase of ? 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.

Patients enrolling onto Arm A (Gemcitabine and nab-Paclitaxel) or Arm B (mFOLFIRINOX) are allowed to have up to two prior lines of systemic therapy, with adjuvant therapy counted as one line of therapy as long as disease recurrence occurred > 6 months of last dose of therapy. Prior systemic therapy in the metastatic setting is allowed for as long as the therapy contained BBI608 in combination with either Gemcitabine and nab-Paclitaxel or mFOLFIRINOX. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible.

Patients enrolling onto Arm C (FOLFIRI) or Arm D (MM-398 with 5-FU and leucovorin) must have failed one prior line of gemcitabine-based therapy with or without BBI608 in the metastatic setting. No additional lines of therapy in the metastatic setting are allowed. Prior adjuvant therapy with gemcitabine is allowed as long as disease recurrence occurred > 6 months of last dose of therapy. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible. Prior treatment with radiotherapy is allowed.

Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to beginning study therapy.

Any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological therapy (including monoclonal antibodies), or experimental anti-cancer therapy) within 28 days prior to beginning study therapy. Note: Ongoing castrating therapy with a GnRH agonist or antagonist is mandatory to assure a castrate level of serum testosterone <50 ng/dL, except in patients who have undergone an orchiectomy. Bisphosphonates or denosumab continuation is permissible (i.e., no change for 30 days prior to Cycle 1 Day 1). Patients who receive a dose of EC1169 under another Endocyte protocol do not need a washout period for EC1169

The subject has received chemotherapy, immunotherapy, or any other systemic anticancer therapy, with the exception of anti-HER2 therapy (e.g., trastuzumab), within 14 days prior to the Day 1 visit.

Prior therapy with lenalidomide

Expected to require any other form of antineoplastic therapy while on study

Subject has received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or anti-cancer herbal therapy within 7 days prior to Cycle 1 Day 1 of ABT-165.

For AML patients, no more than 1 prior salvage therapy.