Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria\r\n* JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis\r\n** Splenomegaly\r\n** > 1000 (1 x 10^9/uL) circulating monocytes\r\n** < 20% blasts in the bone marrow or peripheral blood\r\n** Absence of the t(9;22) or BCR/ABL fusion gene\r\n* JMML category 2 (at least one of the following if at least two category 3 criteria are not present):\r\n** Somatic mutation in RAS or PTPN11\r\n** Clinical diagnosis of NF1 or NF1 gene mutation\r\n** Homozygous mutation in CBL\r\n** Monosomy 7\r\n* JMML category 3 (at least two of the following if no category 2 criteria are met):\r\n** Circulating myeloid precursors\r\n** White blood cell count, > 10 000 (10 x 10^9/ uL)\r\n** Increased hemoglobin F for age\r\n** Clonal cytogenetic abnormality\r\n** GM-CSF hypersensitivity

Patients fulfilling the following criteria will be eligible for entry into this study:

Patients with the following will be ineligible for registration onto this study:

Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.

Study entry PSA should not be obtained during the following time frames:             \r\n* 10-day period following prostate biopsy\r\n* Following initiation of hormonal therapy\r\n* Within 30 days after discontinuation of finasteride\r\n* Within 90 days after discontinuation of dutasteride

A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

Patients with any of the following conditions are NOT eligible for this study.

Patients in the measureable disease cohort must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Pathologically proven diagnosis of any of the following malignancies:

Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:

Phase I (\untreated\ expansion cohort only): no prior HMA and/or lenalidomide treatment Patient has the evidence of symptomatic anemia according to the following criteria:

Patients with AML must be unlikely to benefit from cytotoxic chemotherapy defined by any one of the following criteria:

leukemia in 1st relapse following ? 1 unsuccessful salvage attempts,

Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine

For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:\r\n* Patient is in second salvage or more and B1931022 has been considered and ruled out as a treatment option; OR\r\n* Patient was treated on the standard of care arm of B1931022 and failed therapy

A patient may not participate in a concurrent treatment protocol; all patients will be eligible to receive chemotherapy alone, systemic therapeutic agents, or conventional chemo-radiotherapy at the time of clinical or radiographic disease progression or at 2 weeks following completion of SBRT

A female is eligible to enter and participate in this study if the following apply:

In dose escalation (Phase I), patients must have histologically or cytologically confirmed metastatic disease from any solid tumor that is incurable and fulfills one of the following criteria:\r\n* Has demonstrated progression of disease following at least one line of effective systemic therapy; prior treatment with anti-CTLA-4 antibody (including ipilimumab) is allowable OR\r\n* For which effective therapy does not exist

B-cell lymphoma classified as either of the following: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) monoclonal antibody; R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in participants who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation, have failed second line combination chemotherapy, or experienced disease progression following autologous stem-cell transplantation

Must have one of the following cancers, for which the patient has either received or been intolerant to all therapy known to confer clinical benefit

Failure or intolerance to at least two prior lines of standard chemotherapies with each containing one or more of the following agents:

At the time of study entry, blood counts performed within 2 weeks prior to study entry must meet the following criteria:

Must have transfusion-dependent anemia that meets the following criteria:

Must be unresponsive or refractory to erythropoiesis-stimulating agents (ESA), based on one of the following:

Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject is ?18 years of age at the time of signing the informed consent form (ICF)\n\n          2. Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted\n\n          3. Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements\n\n          4. Subjects must have a documented diagnosis of Multiple myeloma (MM) and have measurable\n             disease by serum and/or urine protein electrophoresis (sPEP or uPEP): sPEP ?0.5 g/dL\n             or uPEP\n\n             ?200 mg/24 hours\n\n          5. All subjects must have received at least 2 prior myeloma regimens (note: induction\n             with or without bone marrow transplant and with or without maintenance therapy is\n             considered one regimen)\n\n          6. All subjects must have received prior treatment with at least 2 consecutive cycles of\n             a lenalidomide or pomalidomide-containing regimen\n\n          7. All subjects must have received prior treatment with at least 2 consecutive cycles of\n             a proteasome inhibitor or a proteasome inhibitor-containing regimen\n\n          8. For Part 2 (Cohort C and Cohort D), all subjects must have received prior treatment\n             with at least 2 consecutive cycles of an anti-CD38 therapy or an anti-CD38-containing\n             regimen\n\n          9. All subjects must have documented disease progression on or within 60 days from the\n             last dose of their last myeloma therapy\n\n         10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2\n\n         11. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at\n             some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has\n             not been naturally postmenopausal (amenorrhea following cancer therapy does not rule\n             out childbearing potential) for at least 24 consecutive months (ie, has not had menses\n             at any time in the preceding 24 consecutive months) and must:\n\n               1. Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after end of study therapy. This applies even if the\n                  subject practices true abstinence* from heterosexual contact.\n\n               2. Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis and source documented) or agree to use, and be able\n                  to comply with two forms of contraception: one highly effective, and one\n                  additional effective (barrier) measure of contraception without interruption 28\n                  days prior to starting investigational product, during the study therapy\n                  (including dose interruptions), and for 28 days after discontinuation of study\n                  therapy. Contraception requirements are detailed in Appendix D.\n\n         12. Male subjects must:\n\n             a. Practice true abstinence* (which must be reviewed on a monthly basis and source\n             documented) or agree to use a condom during sexual contact with a pregnant female or a\n             female of childbearing potential while participating in the study, during dose\n             interruptions and for at least 90 days following the last dose of CC-220, even if he\n             has undergone a successful vasectomy.\n\n             * True abstinence is acceptable when this is in line with the preferred and usual\n             lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation,\n             symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of\n             contraception.]\n\n         13. Males must agree to refrain from donating sperm while on CC-220, during dose\n             interruptions and for at least 90 days following last dose of CC-220.\n\n         14. All subjects must agree to refrain from donating blood while on CC-220, during dose\n             interruptions and for at least 28 days following the last dose of CC-220.\n\n         15. All male and female subjects must follow all requirements defined in the Pregnancy\n             Prevention Program (v5.1).\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study\n\n          2. Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study\n\n          3. Subject has any condition that confounds the ability to interpret data from the study\n\n          4. Subject has nonsecretory or oligosecretory multiple myeloma\n\n          5. Subjects with Plasma Cell leukemia\n\n          6. Any of the following laboratory abnormalities\n\n               -  Absolute neutrophil count (ANC) <1,000/?L\n\n               -  Platelet count <75,000/?L Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)\n\n               -  Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)\n                  or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ?2.0\n                  x upper limit of normal (ULN)\n\n               -  Serum total bilirubin and alkaline phosphatase >1.5 x Upper Limit of Normal (ULN)\n\n               -  Subjects with serious renal impairment (24-hour creatinine clearance [CrCl] <50\n                  mL/min) or requiring dialysis would be excluded\n\n          7. Subjects with peripheral neuropathy ?Grade 2\n\n          8. Subjects with gastrointestinal disease that may significantly alter the absorption of\n             CC-220\n\n          9. Subjects with a prior history of malignancies, other than MM, unless the subject has\n             been free of the disease for ?5 years with the exception of the following noninvasive\n             malignancies:\n\n               -  Basal cell carcinoma of the skin\n\n               -  Squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histological findings of prostate cancer such as T1a or T1b using the\n                  Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer\n                  that is curative\n\n         10. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide,\n             pomalidomide or DEX\n\n         11. Subject has known or suspected hypersensitivity to the excipients contained in the\n             formulation of CC-220 or DEX\n\n         12. Subject has received any of the following within the last 14 days of initiating IP:\n\n               -  Plasmapheresis\n\n               -  Major surgery (as defined by the Investigator)\n\n               -  Radiation therapy other than local therapy for MM associated bone lesions\n\n               -  Use of any systemic myeloma drug therapy\n\n         13. Subject has been treated with an investigational agent (ie, an agent not commercially\n             available) within 28 days or 5 half-lives (whichever is longer) of initiating\n             investigational product (IP)\n\n         14. Subject has any one of the following:\n\n               -  Clinically significant abnormal electrocardiogram (ECG) finding at Screening\n\n               -  Congestive heart failure (New York Heart Association Class III or IV)\n\n               -  Myocardial infarction within 12 months prior to starting IP\n\n               -  Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n                  of angina pectoris\n\n         15. Subject has current or prior use of immunosuppressive medication within 14 days prior\n             to the first dose of IP. The following are exceptions to this criterion:\n\n               -  Intranasal, inhaled, topical or local steroid injections (eg, intra-articular\n                  injection)\n\n               -  Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of\n                  prednisone or equivalent\n\n               -  Steroids as premedication for hypersensitivity reactions (eg, computed tomography\n                  [CT] scan premedication)\n\n         16. Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St.\n             John's Wort or related products within two weeks prior to dosing and during the course\n             of study\n\n         17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or\n             active hepatitis B, or active hepatitis A or C\n\n         18. Subject is unable or unwilling to undergo protocol required thromboembolism\n             prophylaxis\n\n         19. Subject is a female who is pregnant, nursing or breastfeeding

The following diagnoses are to be included:

Subjects must have histologic confirmation of advanced, biopsy-accessible, measurable cancers of the following histologies:

PhaseII : Prior treatment with any of the following agents:

Diagnosis of any of the following:

If sexually active female, patient must be/have one of the following:

Subjects with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at the Screening Visit, the following criteria are met:

Inclusion Criteria\n\n        Each patient must meet all of the following inclusion criteria to be enrolled in the study:\n\n        Phase 1b and Phase 2\n\n          1. Advanced or metastatic breast cancer.\n\n          2. Histological or cytological confirmation of ER+ status (defined as > 1% positive tumor\n             cells), and histological or cytological confirmation of HER2-negative (HER2-) status\n             by local laboratory testing using criteria in the American Society of Oncology\n             (ASCO)/College of American Pathologists (CAP) Clinical Practice Guideline update.[44]\n\n          3. Female patients 18 years of age or older who:Are postmenopausal for at least 1 year\n             before the Screening visit, where menopause is defined by: Age ? 55 years and 1 year\n             or more of amenorrhea\n\n             Age < 55 years and 1 year or more of amenorrhea, with an estradiol assay < 20 pg/mL\n             oSurgical menopause with bilateral oophorectomy\n\n             Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone\n             agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of\n             ovarian suppression.\n\n          4. Patients who have a history of brain metastasis are eligible for the study provided\n             that all the following criteria are met:\n\n               -  Brain metastases which have been treated\n\n               -  No evidence of disease progression for ? 3 months or hemorrhage after treatment\n\n               -  Off-treatment with dexamethasone for 4 weeks before administration of the first\n                  dose of MLN0128\n\n               -  No ongoing requirement for dexamethasone or anti-epileptic drugs\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.\n\n          6. Clinical laboratory values as specified below within 4 weeks before the first dose of\n             MLN0128:\n\n               -  Bone marrow reserve consistent with absolute neutrophil count (ANC) ? 1.5 x\n                  10^9/L; platelet count ? 100 x 10^9/L; hemoglobin ? 9 g/dL\n\n               -  Total bilirubin ? 1.5 x the upper limit of the normal range (ULN), aspartate\n                  aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 x ULN (? 5 x ULN\n                  if liver metastases are present)\n\n               -  Creatinine clearance ? 50 mL/min based either on Cockcroft-Gault estimate or\n                  based on a 12- or 24-hour urine collection\n\n               -  Fasting serum glucose ? 130 mg/dL and fasting triglycerides ? 300 mg/dL\n\n          7. Left ventricular ejection fraction (LVEF) within 5 absolute percentage points of\n             institutional standard of normal as measured by echocardiogram (ECHO) or multiple\n             gated acquisition scan (MUGA) within 4 weeks before the first dose of MLN0128 (ie, if\n             the institutional standard of normal is 50%, LVEF may be as low as 45% to be eligible\n             for the study).\n\n          8. Able to provide paraffin blocks or a minimum of 10 unstained slides of available\n             archival tumor tissues (paraffin blocks are preferred). If archival tumor tissue is\n             not available, a tumor biopsy may be performed before the patient begins treatment\n             with MLN0128. If fewer than 10 slides are available or the tumor content/area\n             requirements are not met, study eligibility will be determined upon discussion with\n             the sponsor.\n\n          9. Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and\n             suitable venous access for the study-required blood sampling.\n\n         10. Voluntary written consent must be given before the performance of any study related\n             procedure not part of standard medical care, with the understanding that consent may\n             be withdrawn by the patient at any time without prejudice to future medical care.\n\n             Phase 1b Only: In addition to the previously mentioned inclusion criteria, each\n             patient must meet the following inclusion criterion to be enrolled in the phase 1b\n             portion of the study:\n\n         11. Patients may have SD or disease progression during their most recent treatment with\n             exemestane or fulvestrant, or everolimus in combination with either exemestane (any\n             country) or fulvestrant (US only). Exemestane or fulvestrant in combination with\n             MLN0128 can also be initiated as a new line of therapy.\n\n             Phase 2 Only: In addition to the previously mentioned inclusion criteria, each patient\n             must meet all of the following inclusion criteria to be enrolled in the phase 2\n             portion of the study:\n\n         12. Measureable disease defined as follows:\n\n               -  At least 1 extra-osseous lesion that can be accurately measured in at least 1\n                  dimension. The lesion must measure ? 20 mm with conventional imaging techniques\n                  or ? 10 mm with spiral CT or MRI, or\n\n               -  Bone lesions (lytic or mixed [lytic plus sclerotic]) in the absence of measurable\n                  disease as defined above\n\n         13. Patients must have had disease progression during treatment with everolimus in\n             combination with either exemestane (any country) or fulvestrant (US only) (duration of\n             treatment ? 4 weeks) and must have tolerated everolimus treatment in combination with\n             exemestane (any country) or fulvestrant (US only) adequately according to the treating\n             physician's judgment. Everolimus in combination with exemestane or fulvestrant is not\n             required to be the most recent treatment before enrollment, but progression on the\n             most recent anticancer therapy is required for enrollment.\n\n        Exclusion Criteria\n\n        Patients meeting any of the following exclusion criteria are not to be enrolled in the\n        study:\n\n        Phase 1b and Phase 2\n\n          1. Prior anticancer therapy or other investigational therapy within 2 weeks before\n             administration of the first dose of MLN0128 (except for exemestane or fulvestrant,\n             which should be continued). Treatment with everolimus must be discontinued 2 weeks\n             before administration of the first dose of MLN0128.\n\n          2. Chronic concomitant therapy with bisphosphonates or denosumab for the prevention of\n             bone metastases. Concomitant treatment with bisphosphonates or denosumab is permitted\n             for treatment of osteoporosis or management of existing bone metastases if initiated\n             at least 4 weeks before administration of the first dose of MLN0128.\n\n          3. Initiation of treatment with hematopoietic growth factors, transfusions of blood and\n             blood products, or systemic corticosteroids (either IV or oral steroids, excluding\n             inhalers) within 1 week before administration of the first dose of MLN0128 (patients\n             already receiving erythropoietin on a chronic basis for ? 4 weeks are eligible).\n\n          4. Previous treatment with dual PI3K/mTOR inhibitors or TORC1/2 inhibitors.\n\n          5. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI\n             disease, or for an unknown reason that may alter the absorption of MLN0128.\n\n          6. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 7%;\n             patients with a history of transient glucose intolerance due to corticosteroid\n             administration may be enrolled in this study if all other inclusion/exclusion criteria\n             are met.\n\n          7. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,\n             active central nervous system disease, active infection, or any other condition that\n             could compromise participation of the patient in the study.\n\n          8. Known human immunodeficiency virus infection.\n\n          9. History of any of the following within the last 6 months before administration of the\n             first dose of MLN0128:\n\n               -  Ischemic myocardial event, including angina requiring therapy and artery\n                  revascularization procedures\n\n               -  Ischemic cerebrovascular event, including transient ischemic attack and artery\n                  revascularization procedures\n\n               -  Requirement for inotropic support (excluding digoxin) or serious (uncontrolled)\n                  cardiac arrhythmia (including atrial flutter/fibrillation, ventricular\n                  fibrillation, or ventricular tachycardia)\n\n               -  Placement of a pacemaker for control of rhythm\n\n               -  New York Heart Association Class III or IV heart failure\n\n               -  Pulmonary embolism\n\n         10. Significant active cardiovascular or pulmonary disease before administration of the\n             first dose of MLN0128, including:\n\n               -  Uncontrolled hypertension (ie, systolic blood pressure > 180 mm Hg; diastolic\n                  blood pressure > 95 mm Hg)\n\n               -  Pulmonary hypertension\n\n               -  Uncontrolled asthma or oxygen saturation < 90% by arterial blood gas analysis or\n                  pulse oximetry on room air\n\n               -  Significant valvular disease; severe regurgitation or stenosis by imaging\n                  independent of symptom control with medical intervention; or history of valve\n                  replacement\n\n               -  Medically significant (symptomatic) bradycardia\n\n               -  History of arrhythmia requiring an implantable cardiac defibrillator\n\n               -  Baseline prolongation of the rate-corrected QT interval (QTc; eg, repeated\n                  demonstration of QTc interval > 480 ms, or history of congenital long QT\n                  syndrome, or torsades de pointes)\n\n         11. Diagnosed or treated for another malignancy within 2 years before administration of\n             the first dose of MLN0128 or previously diagnosed with another malignancy and have any\n             evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in\n             situ of any type are not excluded if they have undergone complete resection.\n\n             Phase 1b Only: In addition to the previously mentioned exclusion criteria, patients\n             meeting the following exclusion criterion are not to be enrolled in the phase 1b\n             portion of the study:\n\n         12. More than 3 prior chemotherapy regimens for locally advanced or metastatic disease.\n\n             Phase 2 Only: In addition to the previously mentioned exclusion criteria, patients\n             meeting the following exclusion criterion are not to be enrolled in the phase 2\n             portion of the study:\n\n         13. More than 1 prior chemotherapy regimen for locally advanced or metastatic disease.

Patients whose disease has progressed following at least 3 cycles of neoadjuvant chemotherapy as defined by at least one of the following:\r\n* Doubling of serum CA-125 level\r\n* At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions\r\n* Clinical deterioration (worsening ascites, carcinomatous ileus, malignant bowel obstruction, severe hypoalbuminemia, declining performance status)

Asparaginase refractory disease, defined by any one of the following:

Inclusion Criteria:\n\n        Key Inclusion Criteria:\n\n        Subjects must meet all of the following criteria to be included:\n\n          1. Male aged between 50 and 80 years (inclusive) with histologically documented\n             clinically localized, adenocarcinoma of the prostate.\n\n          2. Subject with clinical stage T1 or T2 with Gleason score of 6 or 7 (3+4 or 4+3).\n\n          3. At least one (1) MRI evaluable tumor with volume of 400 mm3 or greater.\n\n          4. At least total of 10 mm of cancer tissue based on an MRI guided 12-core biopsy.\n\n          5. Recent (? 6 months prior to study entry) negative bone scan and computerized\n             tomography (CT) scan of abdomen/pelvis.\n\n          6. Life expectancy of at least 5 years.\n\n          7. Subjects should have adequate bone marrow function defined as an absolute peripheral\n             granulocyte count ? 1,500 and platelet count of ? 100,000, adequate hepatic function\n             with a bilirubin ? 1.5 mg/dl and serum glutamic-pyruvic transaminase (SGPT) < 4x the\n             upper limits of normal, adequate renal function defined as serum creatinine ? 2.0\n             mg/dl\n\n          8. Subjects must have a coagulation profile (prothrombin time [PT], partial\n             thromboplastin time [PTT]) not more than 2-times the upper limit of normal and no\n             history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants within\n             5-days of the Ad5-SGE-REIC/Dkk-3 injections is limited to local use only (for control\n             of central line patency).\n\n          9. Subject is willing to refrain from sexual activity or agrees to use a barrier\n             contraceptive device (e.g. condom) for 8-weeks after treatment with\n             Ad5-SGE-REIC/Dkk-3.\n\n         10. Subjects must sign an informed consent indicating that they are aware of the\n             investigational nature of the study.\n\n        Key Exclusion Criteria\n\n        Subjects meeting any of the following criteria will be excluded:\n\n          1. Prior primary radiation treatment to the prostate.\n\n          2. Severe bladder outlet obstructive disorder (AUA >25) or urinary track retention.\n\n          3. Chemotherapy, immunotherapy or other investigational study drug within the past 4\n             weeks.\n\n          4. Unable to tolerate TRUS.\n\n          5. Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric\n             disorders, that in the opinion of the investigator put the subject at significant\n             risk, are not eligible.\n\n          6. Subjects who are HIV positive or have active hepatitis B or C infections are not\n             eligible.\n\n          7. Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune\n             disease or subjects taking immunosuppressive drugs such as corticosteroids\n             continuously for > 4 months [> 5 mg hydrocortisone/day] are ineligible.\n\n          8. As a result of medical review, physical examination, the Principal Investigator (or\n             medically qualified nominee) considers the subject unfit for the study.

Ability to begin treatment in the extension (rollover) protocol within 15 days following the last day of the study in the antecedent protocol

For patients with measurable disease, patient must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

All patients must have at least two of the following diagnostic criteria for NF1, and/or a pathogenic NF1 gene mutation demonstrated in peripheral blood-derived DNA:

Have at least one of the following:

Meets one of the sets of the following criteria:

Either of the following:

Any of the following:

Patients that have had prior treatment must show disease progression during or following the last treatment according to RECIST 1.1 criteria.

Confirmed radiologic disease progression during or following recent treatment

For salivary duct carcinoma patients, the following are required:

Subjects with any of the following solid malignancies:

Treatment with any of the following:

Agree to abstain from donating blood while taking IP and for at least 28 days following discontinuation of IP.

Blood counts performed within 28 days prior to randomization must meet the following criteria:

No evidence of hypercalcemia, renal-failure, anemia and bone-lesions (CRAB) criteria or new criteria of active MM which including the following:\r\n* Increased calcium levels (corrected serum calcium > 0.25 mmol/dL above the upper limit of normal or > 0.275 mmol/dL)\r\n* Renal insufficiency (attributable to myeloma)\r\n* Anemia (hemoglobin [Hb] 2 g/dL below the lower limit of normal or < 10 g/dL)\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* No evidence of the following new criteria for active MM including the following: bone marrow plasma cells > 60%, serum involved/uninvolved FLC ratio >= 100, and magnetic resonance imaging (MRI) with more than one focal lesion\r\n** Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible

Inclusion Criteria:\n\n        Subjects must meet the following criteria to be included:\n\n          -  Willing and able to read, understand and sign an informed consent form\n\n          -  Confirmed diagnosis by enrolling physician of WAIHA\n\n          -  Must use medically acceptable contraception\n\n        Exclusion Criteria:\n\n        Subjects meeting any of the following criteria are to be excluded:\n\n          -  Subject unable or unwilling to comply with the protocol\n\n          -  Active non-hematologic malignancy or history of non-hematologic malignancy in the 3\n             years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in\n             situ)\n\n          -  Positive for HIV or hepatitis C antibody\n\n          -  Positive for hepatitis B surface antigen\n\n          -  Any exposure to an investigational drug or device within the 30 days prior to\n             screening\n\n          -  IVIG treatment within 60 days of screening\n\n          -  Plasmapheresis or immunoadsorption within 60 days of screening\n\n          -  Subject has any current medical condition that, in the opinion of the Investigator,\n             may compromise their safety or compliance, preclude successful conduct of the study,\n             or interfere with interpretation of the results

Inclusion Criteria:\n\n        Subjects are eligible to be included in the study only if they meet all of the following\n        criteria:\n\n          1. Subjects who are males or females ? 18 years of age.\n\n          2. Subjects who are able to give written informed consent.\n\n          3. Subjects who have a documented diagnosis of MDS according to WHO criteria.\n\n          4. Subjects who have Revised International Prognostic Scoring System (IPSS-R) categories\n             of Very Low, Low- or Intermediate-risk disease. Subjects with cytogenetic failure and\n             ? 10% marrow blasts will be eligible.\n\n          5. Subjects who meet one of the following hematologic criteria within 8 weeks of\n             registration (according to the IWG criteria) and as documented in prior transfusion\n             logs or weekly hematology evaluations:\n\n               -  Symptomatic anemia untransfused with hemoglobin ? 9.0 g/dL or with RBC\n                  transfusion-dependence (i.e., ? 2 units/month) confirmed for a minimum of 8 weeks\n                  before randomization.\n\n               -  Platelet counts of < 100 x109/L\n\n               -  Absolute neutrophil count < 1500\n\n          6. Subjects with del(5q) who should have failed or not be a candidate for approved\n             therapy (Lenalidomide) prior to enrolling on this study.\n\n          7. Subjects must meet accepted standard criteria for treatment and have failed or not be\n             candidates for standard, accepted treatments.\n\n          8. Subjects who have sufficient hepatic function, defined as bilirubin 2 times the upper\n             limit of normal (ULN) and alanine transaminase (ALT) and aspartate transaminase (AST)\n             levels 2.5 times ULN.\n\n          9. Subjects who have sufficient renal function, defined as serum creatinine levels 1.5\n             ULN.\n\n         10. Subjects who have a performance status of 2 on the Eastern Cooperative Oncology Group\n             (ECOG) scale (refer to Appendix 2).\n\n         11. Subjects who have discontinued all previous therapies for MDS or other investigational\n             therapy for at least 28 days prior to study enrollment and recovered to less than\n             grade 2 toxicity from prior therapy.\n\n         12. Subjects who are able to swallow tablets.\n\n         13. Subject who are willing and able to comply with scheduled visits, treatment plans,\n             laboratory tests and procedures.\n\n         14. Female subjects of childbearing potential must have a negative serum pregnancy test\n             within 7 days of the first administration of study drug. For the purpose of this\n             study, female subjects of childbearing potential are defined as all female subjects\n             after puberty unless they are postmenopausal for at least 1 year, or are surgically\n             sterile (hysterectomy or bilateral oophorectomy or tubal ligation).\n\n         15. Female subjects of child bearing potential who are willing to avoid the pregnancy\n             during the duration of the study and for 30 days following the last dose of study\n             drug. The effects of TEW-7197 on the developing human fetus are unknown. For this\n             reason, women of child-bearing potential and men must agree to use adequate\n             contraception (hormonal or barrier method of birth control; abstinence) prior to study\n             entry and for the duration of study participation. Should a woman become pregnant or\n             suspect she is pregnant while participating in this study, she should inform her\n             treating physician immediately.\n\n         16. Subjects with QTc interval calculated according to Fridericia's formula (QTcF =\n             QT/RR0.33; RR = RR interval) of ? 470 ms for males and 450 ms for females on screening\n             electrocardiogram (ECG).\n\n         17. Subjects must have ejection fraction more than 50% and no clinically significant\n             valvular dysfunction.\n\n         18. Subjects must have discontinued radiotherapy at least 14 days with resolution of any\n             toxicity to Grade 1 or better prior to the start of treatment.\n\n        Exclusion Criteria:\n\n        Subjects will be excluded from the study if they meet any of the following criteria:\n\n          1. Subjects who have received treatment within the last 28 days with a drug that has not\n             received regulatory approval for any indication at the time of study entry.\n\n          2. Subjects who have moderate or severe cardiac disease:\n\n          3. Subjects who have the presence of cardiac disease, including a myocardial infarction\n             within 6 months prior to study entry, unstable angina pectoris, New York Heart\n             Association (NYHA) Class III/IV congestive heart failure, or uncontrolled\n             hypertension.\n\n          4. Subjects who have documented major electrocardiogram (ECG) abnormalities at the\n             investigator's discretion (for example, symptomatic or sustained atrial or ventricular\n             arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks,\n             ventricular hypertrophy, or recent myocardial infarction).\n\n          5. Subjects who have major abnormalities documented by echocardiography with Doppler (for\n             example, moderate or severe heart valve function defect and/or left ventricular\n             ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of\n             normal).\n\n          6. Subjects who have predisposing conditions that are consistent with development of\n             aneurysms of the ascending aorta or aortic stress (for example, family history of\n             aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large\n             vessels of the heart documented by CT scan with contrast).\n\n          7. Subjects who have documented iron, B12, folate deficiency as determined by the\n             investigator.\n\n          8. Female subjects who are breastfeeding, or intend to breastfeed during the duration of\n             the study and for 30 days following the last dose of study drug.\n\n          9. Subjects with any other serious medical condition which in the Investigator's opinion\n             would preclude safe participation in the study.\n\n         10. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the\n             study.\n\n         11. Subjects with elevated Troponin 1 levels at screening or known to have persistently\n             elevated brain natriuretic peptide (BNP).\n\n         12. Subjects with serious pre-existing medical conditions as follows:\n\n               -  History of cardiac or aortic surgery,\n\n               -  Hypertension that is not controlled by standard medication (to 150/90 mmHg or\n                  below),\n\n               -  Cirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,\n\n               -  Severe diabetes that is not currently controlled,\n\n               -  Current or history of interstitial pneumonitis,\n\n               -  Presence of aneurisms of the ascending aorta or aortic stress.\n\n         13. Subjects with known history of difficulty swallowing, malabsorption or other\n             conditions that may reduce absorption of the product.\n\n         14. Subjects with major abnormalities identified by ECG or echocardiogram (ECHO), at the\n             Investigator's discretion.\n\n         15. Subjects with active infection with human immunodeficiency virus, hepatitis B virus or\n             hepatitis C virus.\n\n         16. Subjects with active infection requiring systemic antibiotic therapy.\n\n         17. Subjects who are currently using or planning to use:\n\n        Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4

Adequate coagulation functioning within 28 days prior to study registration defined by either of the following criteria:

Patients must have available two UCB units fulfilling the following criteria:

Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization [FISH]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:

One of the following:

Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following:

History of any of the following within the last 6 months before administration of the first dose of the study drugs:

Patients must fulfill one of the following:

Post-menopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.

Treatment with any of the following:

Two out of three of the following (in peripheral blood): Neutrophils < 0.5 x10^9/L, Platelets < 20 x10^9/L, or Reticulocyte count < 20 x10^9/L

CMR following S1 chemotherapy

Each patient must meet the following criteria:

Patients must not meet any of the following criteria:

Induction chemotherapy was administered with any combination of the following agents:

Inclusion Criteria:\n\n        To be eligible for this study, a patient must meet all of the following inclusion criteria:\n\n          1. Be at least 18 years of age.\n\n          2. Has signed the current approved informed consent form.\n\n          3. Has a histologically confirmed diagnosis of malignant melanoma.\n\n          4. Has at least two separate cutaneous lesions suitable for punch biopsies (at least 3 mm\n             diameter).\n\n          5. For women of childbearing potential and men, agree to use a highly effective method of\n             contraceptive from screening, through the study, and for at least 4 weeks after the\n             last dose of study drug.\n\n          6. For women of childbearing potential, must have a negative pregnancy test (serum or\n             urine) on Day 1 prior to initiating study treatment, and are not nursing.\n\n          7. Be willing and able to comply with the schedule, treatment, and biopsies specified by\n             this protocol.\n\n        Exclusion Criteria:\n\n        Patients with any of the following will be excluded from participation in the study:\n\n          1. Has performance status Grade 2 or higher (Eastern Cooperative Oncology Group [ECOG]\n             criteria).\n\n          2. Has ongoing acute clinical adverse events NCI CTCAE Grade 2 or greater resulting from\n             prior cancer therapies (except alopecia).\n\n          3. Has had within the past 6 months the occurrence or persistence of one or more of the\n             following medical conditions that could not be controlled with usual medical care\n             (e.g., required emergency care or hospitalization): angina, congestive heart failure,\n             diabetes, seizure disorder.\n\n          4. Has had within the past 6 months the occurrence of one or more of the following\n             events: myocardial infarction, cerebrovascular accident, hemorrhage (CTC Grade 3 or\n             4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), a second\n             active malignancy requiring ongoing treatment during the trial, organ transplantation.\n\n          5. Has had within the 4 weeks prior to initiation of study drug, or is expected to have\n             during the study period, surgery requiring general anesthesia\n\n          6. Has, at screening, serologic laboratory tests meeting one or more of the following\n             criteria:\n\n               -  An indeterminate or positive test for antibody to human immunodeficiency virus\n                  (HIV-1 or -2).\n\n               -  An indeterminate or positive test for antibody to hepatitis C virus (HCV), unless\n                  documented to have no detectable viral load on two independent samples.\n\n               -  A positive test for hepatitis B surface antigen (HBsAg).\n\n          7. Has, at screening, safety laboratory tests meeting one or more of the following\n             criteria:\n\n               -  Hemoglobin <9.0 g/dL\n\n               -  Absolute neutrophil count (ANC) <1,500/?L\n\n               -  Platelets <100,000/?L\n\n               -  Creatinine >2.0x ULN\n\n               -  Serum aspartate transaminase (AST) >3x ULN\n\n               -  Serum alanine transaminase (ALT) >3x ULN\n\n               -  Total bilirubin >1.5x ULN (unless due to Gilbert's Syndrome)\n\n               -  International normalized ratio (INR) >1.5x ULN (unless on therapeutic\n                  anti-coagulation).\n\n          8. Has been previously treated with approved or investigational immunotherapy including\n             oncolytic viruses, or agents directed at CTLA-4, PD-1, or PD-L1 (\checkpoint\n             inhibitors\).\n\n          9. Has previously received other anti-cancer therapy within 2 weeks prior to Day 1,\n             including radiation therapy or chemotherapy. For investigational anti-cancer\n             therapies, the interval will be determined in consultation with the Medical Monitor.\n\n         10. Has, within 2 weeks prior to Day 1, been regularly taking a medication prohibited\n             based on CYP3A4 interaction.\n\n         11. Has, at the planned initiation of study drug, an uncontrolled infection.\n\n         12. Has any other medical or personal condition that, in the opinion of the Investigator,\n             may potentially compromise the safety or compliance of the patient, or may preclude\n             the patient's successful completion of the clinical trial.

Histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy:

For subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT

For subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation

The study will include three primary cohorts, with any of the following EBV+ diseases: Cohort A - DLBCL, 1) in first or subsequent relapse, not eligible for autologous transplantation following salvage therapy OR 2) relapse following autologous transplantation. Cohort B - HL, brentuximab vedotin (BV) treatment failure or unable to tolerate BV. Cohort C - PTLD, rituximab treatment failure.

Relapse or progression following previous autologous EBV specific T cell treatment.

For post immunotherapy patients with NSCLC all of the following apply:

For other post immunotherapy patients all of the following must apply:

For immune checkpoint naïve CRPC patients all of the following must apply:

For immune checkpoint naïve patients all of the following must apply:

For other immune checkpoint naïve tumor cohort all of the following must apply:

Treatment with any of the following:

Histopathologically confirmed diagnosis of one of the following:

Current or planned glucocorticoid therapy, with the following exceptions:

Patients eligible for resection with one or more of the following

Disease Status: Patients must have ONE of the following:

Any episode of recurrent disease following completion of aggressive multi-drug frontline therapy.

Clinical diagnosis of one of the following:

Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as:\r\n* Adjuvant therapy for ALL (group A), or\r\n* Treatment for relapsed/residual ALL disease (group B)

Subject must have the following staging requirements:

Tumor: patient must have one of the following diagnoses to be eligible:

Patients from Stratum I who fulfill the following criteria:

Patients from Stratum I or Stratum III who fulfill the following criteria:

The presence of any of the following criteria will exclude the patient from the study:

Documented disease progression following prior therapy, as assessed by the Investigator.

In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:

Lab results per the following within 4 weeks prior to study registration:

Patient's medical history does not contraindicate treatment with at least one of the following antibiotics: ampicillin, clindamycin and erythromycin/clarithromycin.

All subjects must fulfill one of the following:

Meet the following disease activity criteria:

Documented progression to prior therapies: a) Cohort A: Disease progression following prior immune checkpoint blockade therapy; b) Cohort B: Progression or intolerance to at least 2 prior lines of standard therapy for unresectable or metastatic CRC; c) Cohort C: Disease progression following prior immune checkpoint blockade therapy.

Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments

If the study Sponsor decides to evaluate additional solid tumors, subjects must satisfy following criteria to be included in the study: Has a pathologically documented advanced solid tumor.

Adequate hepatic function as evidenced by: serum total bilirubin ?1.5 × ULN unless considered due to Gilbert's disease, a gene mutation in UGT1A1 (only for patients who will be receiving AG-221), or leukemic involvement following approval by the study Sponsor; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?3.0 × ULN, unless considered due to leukemic involvement following approval by the study Sponsor

Relapsed or refractory B-precursor ALL defined as one of the following:

Dose Escalation Portion: Patients must satisfy one of the following criteria:

Dose Expansion Portion: Patients must satisfy one of the following criteria:

Arm C: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor.

Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)

The subject must have experienced at least one of the following:

If post allogeneic HCT: Confirmed CD19+CD22+ leukemia recurrence defined as >= 0.01% disease following allogeneic HCT

Any of the following:\r\n* Pregnant persons\r\n* Nursing persons

Inclusion Criteria\n\n        Subjects must fulfil all of the following requirements:\n\n          1. A histologically or cytologically confirmed cancer that is metastatic and is approved\n             to be treated with Nivolumab or Atezolizumab with the following origins: melanoma,\n             NSCLC, HNSCC, RCC, and urothelial cancer, as well as the following:\n\n               1. Subjects must not be considered eligible for a potentially curative resection.\n\n               2. Subjects who are eligible for PD-1/PD-L1 therapy or who have exhausted all\n                  standard therapies for their disease except for immunotherapy.\n\n                  either c) or d)\n\n               3. Subjects progressed on their prior treatment before initiating treatment on\n                  current study.\n\n                  Or\n\n               4. Subjects, who are currently being treated with PD-1 or PD-L1 inhibitors Nivolumab\n                  or Atezolizumab and have achieved at least stable disease (SD), and who, in the\n                  judgment of their treating physicians, could benefit from the addition of\n                  DSP-7888 vaccine to improve or maintain their response.\n\n             In expansion part only: All subjects who are candidates for immunotherapy including\n             PD-1/PD-L1 inhibitors are eligible to enroll in the study. Subjects must have at least\n             1 target lesion based on RECIST criteria and other supporting disease specific\n             evaluation criteria.\n\n          2. Subjects must be positive for at least 1 of the following human leukocyte antigens\n             (HLA):\n\n               1. HLA-A*02:01\n\n               2. HLA-A*02:06\n\n               3. HLA-A*24:02\n\n          3. ? 18 years of age.\n\n          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n\n          5. Either archival tumor tissue must be available or subject must consent to undergo a\n             tumor biopsy before administration of first dose.\n\n          6. Females of childbearing potential must have a negative serum pregnancy test.\n\n          7. Male or female subjects of child-producing potential must agree to use contraception\n             or use prevention of pregnancy measures (true abstinence) during the study and for 150\n             days after the last dose.\n\n          8. Total bilirubin of ? 2.0 mg/dL (? 3.0 mg/dL for subjects with known Gilbert's\n             syndrome)\n\n          9. Aspartate aminotransferase (AST) ? 3.0 × the upper limit of normal (ULN) or < 5 × ULN\n             if considered to be due to liver metastases.\n\n         10. Alanine transaminase (ALT) ? 3.0 × the upper limit of normal (ULN) or < 5 × ULN if\n             considered to be due to liver metastases.\n\n         11. Glomerular Filtration Rate > 40 mL/min.\n\n         12. Multigated acquisition (MUGA) scan or echocardiogram with left ventricular ejection\n             fraction (LVEF) > 40%.\n\n         13. Life expectancy ? 3 months.\n\n         14. Subjects must be willing to provide a personally signed and dated informed consent\n             document.\n\n        Exclusion Criteria\n\n        Subjects with any of the following will be excluded from the study:\n\n          1. Anticancer chemotherapy (including molecular targeted drugs), immunotherapy, or\n             investigational agents within 7 days of the first dose of DSP-7888; radiotherapy\n             within 4 weeks of the first dose of DSP-7888. Subjects may begin DSP-7888 on a date\n             determined by the Investigator and medical monitor for the Sponsor provided that all\n             treatment related adverse events (AEs) have resolved or have been deemed irreversible.\n             This exclusion is not applied to subjects who meet the inclusion criterion 1d.\n\n          2. In expansion part only: Subjects progressed on their prior checkpoint inhibitors\n             (PD-1/PD-L1) treatment before initiating treatment on current study.\n\n          3. Major surgery within 4 weeks prior to study treatment.\n\n          4. Subject has received a live vaccine within 30 days prior to the first dose.\n\n          5. Any known, untreated brain metastases. Subjects with treated brain metastases must be\n             clinically stable for 4 weeks after completion of treatment for brain metastases and\n             have radiographic image documentation of stability. Subjects must have no clinical\n             symptoms from brain metastases and not have required systemic corticosteroids > 10\n             mg/day prednisone or equivalent for at least 2 weeks prior to the first dose of study\n             drug.\n\n          6. Subject has multifocal glioblastoma.\n\n          7. Pregnant or breastfeeding.\n\n          8. Subject has an active autoimmune disease requiring immunosuppression with the\n             exception of subjects with isolated vitiligo, resolved childhood asthma or atopic\n             dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid subjects with\n             a history of Grave's disease.\n\n             a. Subjects with controlled hyperthyroidism must be negative for thyroglobulin and\n             thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to study\n             drug administration.\n\n          9. Subject has interstitial lung disease or active, non-infectious pneumonitis.\n\n         10. Known hypersensitivity to a component of protocol therapy.\n\n               1. Subjects with known hypersensitivity to any of the components of DSP-7888 Dosing\n                  Emulsion.\n\n               2. Subjects with known hypersensitivity to Nivolumab or Atezolizumab are excluded\n                  from receiving combination therapy that includes the agent to which they are\n                  hypersensitive.\n\n         11. Uncontrolled concurrent illness including, but not limited to, ongoing or active\n             infection, clinically significant non-healing or healing wounds, symptomatic\n             congestive heart failure, unstable angina pectoris, severe and/or uncontrolled cardiac\n             arrhythmia, significant pulmonary disease, uncontrolled infection or psychiatric\n             illness/social situations that would limit compliance with study requirements.\n\n         12. Subjects with a history of another primary cancer with the exception of: a) curatively\n             resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;\n             c) localized prostate cancer not requiring systemic therapy; and d) any another cancer\n             from which the subject has been disease free for ? 2 years that, in the opinion of the\n             Investigator and medical monitor for the Sponsor, will not affect subject outcome in\n             the setting of the current diagnosis.\n\n         13. Patient has a QTcF (QT corrected based on Fridericia's equation) interval > 480 msec\n             (CTCAE = Grade 2) or other factors that increase the risk of QT prolongation or\n             arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT\n             interval syndrome) at screening. (Patients with bundle branch block and a prolonged\n             QTc interval should be reviewed by the Medical Monitor for potential inclusion.)\n\n         14. Subject has a medical history of frequent or sustained ventricular ectopy.\n\n         15. Subject has, in the opinion of the treating Investigator, any concurrent conditions\n             that could pose an undue medical hazard or interfere with the interpretation of the\n             study results.\n\n         16. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or\n             untreated hepatitis C; patients who have completed a course of anti-viral treatment\n             for hepatitis C are eligible.\n\n         17. Subject has baseline signs and symptoms consistent with clinically significant,\n             decreased pulmonary function: (1) blood saturation oxygen level (SpO2) < 90% at rest\n             on room air; (2) dyspnea at rest or required supplemental oxygen within 2 weeks of\n             study enrollment.

Unwilling to use approved contraception for at least 6 months following transplant

Metastatic colorectal cancer patients have progressed following at least one line of fluorouracil (5-FU)-based chemotherapy

Any of the following concomitant diseases/conditions:

Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Patients must meet at least one of the following AVPC criteria: \r\n* Histologically proven small cell (neuroendocrine) prostate carcinoma.\r\n* Exclusive visceral metastases. \r\n* Predominantly lytic bone metastases identified by plain x-ray or CT scan. \r\n* Bulky (>= 5 cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. \r\n* Low PSA (=< 10 ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases. \r\n* Elevated serum lactate dehydrogenase (>=2 x upper limit of normal) or elevated serum carcinoembryonic antigen (>= 2 x upper limit of normal) in the absence of other etiologies. \r\n* Short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy. \r\n* Known loss or mutation (by Clinical Laboratory Improvement Act [CLIIA] certified molecular testing, immunohistochemistry staining method [IHC] and/or DNA sequencing) in at least 2 of the following: Tp53, RB1 and PTEN.

Females of childbearing potential must agree and meet the following conditions below: to

Subject has previously received (presence of any of the following will exclude a subject from enrollment):

Has received treatment with any of the following:

Investigator determined assessment of current stable disease following completion of at least 4 cycles but no more than 8 cycles, of pembrolizumab monotherapy

Have had or are planning to have the following invasive procedures:

If post allogeneic HCT: confirmed CD22+ leukemia recurrence defined as >= 0.01% disease by following allogeneic HCT

histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy: DLBCL (regardless of cell of origin or underlying molecular genetics), MCL, PMBCL, Gr3b-FL, TH-FL (prior dx of FL before transforming to DLBCL).

biopsy-confirmed CD20+ expression of the underlying malignancy with disease progression following immediate prior therapy

for subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT

for subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation

Low-risk HPV+ disease, defined as meeting all of the following criteria:\r\n* Patients with HPV+ by fluorescence in situ hybridization (FISH) and/or p16\r\n* Smoking history =< 10 pack years\r\n* Stage T1-2N0-2b, T3N0

Progressive disease at study entry defined as 1 or more of the following 3 criteria:

Adequate haematological and end-organ function, as per the local institutions reference ranges, within 72 hrs prior to day 1 of cycle 1 of treatment defined by the following:

Subjects with any of the following conditions are excluded:

History of symptomatic CTCAEv4 grade >= 3 pneumonitis following the initial course of definitive radiation therapy

Experienced progression following a regimen containing an alkylating agent.

Progression following standard combined modality treatment with radiation and temozolomide chemotherapy

Refractory to or intolerant of lenalidomide maintenance following first autologous stem cell transplantation; refractory is defined as disease relapse/progression on therapy or within 60 days of completing therapy; intolerance is defined as the inability to administer >= 10 mg per day due to toxicity

Have relapsed, refractory, or progressive disease following last line of treatment

Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:

Any one of the following:

SY-1425 and daratumumab combination only - Subject has either of the following:

Use of the following:

Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this includes, but is not restricted to, subjects with any of the following:

Patients must have radiological evidence of disease progression following the most recent treatment

For patients undergoing curative intent resection the following criteria are required:

Subjects must meet all of the following criteria to be included in this study:

Subjects who meet any of the following criteria will be excluded from this study:

Disease status must be 1 of the following:

Post-menopausal: defined as more than 50 years-of-age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments

Patient must have a 12-lead ECG with ALL of the following parameters at screening:

Histologically documented diagnosis of Ph+ CML, in accelerated or blast phase. One of the following parameters is required to meet criteria for accelerated CML:

Patients must have the following lab values obtained < 4 weeks prior to starting treatment:

Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:

Poor prognosis disease as defined by any of the following:\r\n* PSA nadir >=4.0, or\r\n* Gleason score 8-10, or\r\n* Time from ADT initiation to CRPC of =< 16 months

Screening blood counts of the following:

Screening chemistry values of the following:

For Phase 1a LY3300054 monotherapy or combination therapy, previous immunotherapy is acceptable if the following criteria are met:

Loss of MMR following a first TKI discontinuation trial

All patients must use adequate contraception during participation in this trial and for 3 months following completing therapy

History of a previous treated cancer except for the following:

Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:

For Part 2 and Part 3 of the study, participants must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Participants will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following participants with relapsed DLBCL will be enrolled:

Patients must have either of the following:

Treatment with any of the following:

Participants with preoperatively staged T3, N1, or N2 tumors who return > 12 weeks following completion of neoadjuvant chemoradiation therapy (CRT)

Refractory or relapsed myeloma, defined as one or more of the following: \r\n* Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following: \r\n** Less than partial response (PR) to first-line therapy\r\n** Relapse after first (1st) line therapy\r\n* High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)\r\n* Relapse after a prior autologous stem cell transplant (ASCT)\r\n* Plasma cell leukemia\r\n* Soft tissue plasmacytoma

Failure of at least one line of systemic anti-cancer therapy for advanced NSCLC defined as either of the following: \r\na) Radiological documentation of disease progression (or failure to achieve a response) or \r\nb) Discontinuation due to toxicity

Serum biochemical values with the following limits unless considered due to leukemia:

Patients are required to meet the following criteria to proceed to AHSCT:

Patients must have documentation of a defined initial progression free interval (PFI 1) of greater than 6 months following front-line therapy

DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following:

Use of any of the following after transplantation and prior to starting study therapy:

Patients for whom busulfan/melphalan consolidation therapy following treatment with 131I-MIBG is planned

Progression following platin, 5-FU, cetuximab and taxane given for incurable disease

Patients must have at least one of the following criteria:\r\n* The serum PSA should be greater than or equal to 20 ng/ml OR study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of antiandrogen therapy (ADT)\r\n* The Gleason score should be greater than or equal to 8 OR\r\n* Eligible patients must have appropriate staging studies identifying them as American Joint Committee on Cancer (AJCC) stage T3+ adenocarcinoma of the prostate gland; (MR stage T3a without other high risk factors permitted at investigator discretion)

Participants for the phase 2 portion of the study must, in addition, meet the following: o Must be refractory to or relapsed after no more than 2 prior chemotherapy regimens. Re-induction with the same regimen or stem cell transplant will not be considered a separate regimen.

Use or consumption of any of the following substances:

Males and females 65 years of age and older; subjects < 65 years of age that meet any of the following criteria: \r\n* Subjects that refuse to be treated with chemotherapy based agents (this should be documented in the consent form)\r\n* Subjects that are not candidates for treatment with chemotherapy agents based on any of the following:\r\n** ECOG performance status >= 2\r\n** Cumulative illness rating scale (CIRS score) >= 6\r\n** Creatinine clearance < 70 mL/min using the Cockcroft-Gault equation

Unresolved immune-related adverse events following prior biological therapy

Serum biochemical values with the following limits unless considered due to leukemia:

At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria:

Patients receiving neo-adjuvant chemotherapy whose disease has progressed following at least 3 cycles, defined by at least one of the following: clinical deterioration (new or worsening of existing ascites, carcinomatous ileus, malignant bowel obstruction, declining performance status), new lesion(s) or increase in maximal diameter of > 20% of the two largest target lesions, rising CA-125 (an increase of at least 10% of baseline value that increases over 3 values obtained every 21 days)

Patients must have at least ONE of the following sites of disease:

Minimum of six weeks is required following prior therapeutic doses of MIBG.

No response, progression, or relapse (according to 2006 International Working Group [IWG] criteria) following at least 4 cycles of either azacitidine or decitabine, which were completed within the last 2 years - AND/OR - intolerance to azacitidine or decitabine defined as drug-related >= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years

Documentation of recurrence/progression/residual disease following prior therapy

First episode of recurrent disease following completion of aggressive multi-drug frontline therapy.

Each patient must satisfy at least one of the following criteria:

Patient must also satisfy at least one of the following criteria:

Patients must meet the following clinical criteria to receive CMVpp65-CTL infusions

Patient must also satisfy at least one of the following criteria:

Diagnosis of AML associated with the following karyotypes: inversion (inv)(16), t(16;16), t(8;21), t(15;17), or t(9;22)

Be an appropriate candidate for receiving RFA as a medically indicated treatment as evaluated by the following factors:

Study entry PSA should not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of hormonal therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days after discontinuation of dutasteride

The subject has a histologic or cytologic diagnosis of a DTC tumor (including poorly differentiated thyroid cancer but not anaplastic thyroid cancer) that is metastatic or unresectable and fulfills the following criteria:\r\n* Subjects must have progressive disease as defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria when comparing baseline scans to those obtained within the prior 14 months AND\r\n* Subject must have radioiodine (RAI)-refractory disease based on at least one of the following:\r\n** Prior dose of RAI exceeding 600mCi\r\n** Progression of disease within 18 months following a dose of >= 100mCi\r\n** Presence of target lesions as defined by modified RECIST criteria which do not take up RAI

Evidence of progression or lack of response following at least 1 prior treatment for indolent lymphoma

Patient agrees to receive a 5 year minimum course of endocrine therapy following cryoablation for control of systemic disease

Progression by RANO criteria following all standard treatment options with known survival benefit

Anergic, defined by the inability to make a Delayed-type Hypersensitivity (DTH) to at least one of the following: candida, mumps, tetanus or trichophyton (based upon availability)

Combination of any two of the following (a+b or a+c, or b+c):

Patients must have relapsed or refractory disease after at least one prior therapy and not have traditional options available or decline these. All patients must meet all of the following inclusion criteria to be enrolled on the study:

Evidence of measurable (macroscopic) residual disease following hysterectomy and lymphadenectomy

Inclusion Criteria:\n\n        All subjects must meet the following criteria for admission into the study:\n\n          1. Signed informed consent has been obtained.\n\n          2. Subject is at least 21 years of age.\n\n          3. Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS) will be based on a\n             combination of histological, clinical, and immunophenotypical criteria. The\n             histological criteria will be based on skin biopsy from the most representative skin\n             area. The diagnostic criteria used for each subject will be specified in the case\n             report forms and the specific classification of MF or SS will be identified. The TNMB\n             system will be used to classify the stage of disease (See Section 8.4 for details).\n\n          4. Completion of the mSWAT assessment.\n\n          5. A history of pruritus that meets following criteria:\n\n             At Screening Day -7:\n\n               -  present on a daily basis for greater than one month prior to Screening Day -7,\n\n               -  NRS for Pruritus score ?5 as rated by the subject at the Day -7 Visit. Note: If\n                  the score is <5 and subject is taking or has taken a medication which may be\n                  affecting pruritus (e.g. systemic antihistamine or topical steroid), and if\n                  Investigator and subject agree, subject may washout or continue washout of\n                  medication and return for Day -7 Visit procedures after washout.\n\n             At Baseline Period 1 Day 0:\n\n               -  NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4\n                  of the 7 days preceding Baseline Period 1 Day 0.\n\n          6. Pruritic treatment area of 5-95% of the subject's total treatable body surface area.\n\n          7. Subject can be expected to reliably follow treatment instructions and visit schedule.\n\n          8. Non-pregnant, non-lactating females of childbearing potential who agree to use\n             medically acceptable forms of birth control (abstinence, hormonal contraceptives,\n             diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout\n             the study or females of non-childbearing potential (surgically sterile [hysterectomy\n             or bilateral tubal ligation] or post-menopausal ? 1 year). A negative urine pregnancy\n             test must be confirmed at Baseline screening for all female subjects who are not\n             post-menopausal > 1 year or surgically sterile.\n\n          9. The subject agrees not to begin any new concomitant medications during their\n             participation in the study, with the exception of medications necessary to treat\n             infection, and to continue any concomitant medication throughout the study.\n\n         10. Subject has no visual or motor impairments that will make it difficult to complete the\n             Daily Diary or apply the study medication.\n\n         11. Subject is able to speak, read, and write English and agrees to participate and comply\n             with the study procedures.\n\n         12. Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (see Appendix C, Body\n             Mass Index Table) (subjects in PK subset only).\n\n        Exclusion Criteria:\n\n        Subjects meeting any of the following criteria will be excluded from study participation:\n\n          1. Pregnant or lactating female.\n\n          2. History of clinically significant heart failure.\n\n          3. Myocardial infarction within the past six months.\n\n          4. A history of ventricular arrhythmia requiring treatment.\n\n          5. Any medical condition which would, in the Investigator's opinion, preclude the subject\n             from successfully participating in the study.\n\n          6. A known allergy to naloxone hydrochloride or any excipient in the formulation.\n\n          7. Previous naloxone use for pruritus.\n\n          8. Positive urine drug screen at Day 0 for opiates. Positive urine drug screen for\n             anything other than opiates not explained, e.g., by concomitant medication, would also\n             exclude the subject.\n\n          9. Treatment with any of the following during the restricted time period prior to Day -7,\n             and at any time during the study, is not allowed:\n\n        Medication/Treatment Restriction:\n\n        Systemic narcotic analgesics (e.g. morphine, codeine) 7 days, Topical antihistamines to any\n        skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any\n        therapies for the treatment of MF or SS) 30 days

Have one of the following documented by a local test:

Have one of the following documented by a local test:

Those receiving prior immunotherapy must meet all of the following conditions:

The combination of any 2 of the following methods when both are used simultaneously:

(Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Relapsed, refractory, or progressive disease, specifically: (a) Solid tumors: Following at least 1 prior systemic therapy, and no further standard therapy is available for the patient's advanced solid tumor at the time of enrollment; or (b) Classical HL: Following at least 2 prior systemic therapies in patients who are not candidates for autologous stem cell transplant (SCT), or following failure of autologous SCT; or (c) DLBCL: Following at least 1 prior systemic therapy; patients must have also received intensive salvage therapy unless they refused or were deemed ineligible; or (d) Indolent lymphoma: Following at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists

Willingness to participate in rigorous neurocognitive evaluations at baseline and serially following treatment

Study entry PSA and serum testosterone must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of oral androgen manipulation; (3) within 30 days after discontinuation of finasteride or dutasteride

Known or suspected progressive disease following autologous SCT

In patients 18-60 years of age, moderately severe aplastic anemia is defined as having at least one of the following:\r\n* Platelet count < 20 x 10^9/L\r\n* ANC < 5 x 10^8/L\r\n* Hgb < 8 g/dL

Recipients will fall under one of the following disease categories:

Must have MLL gene rearrangements documented by split-signal fluorescence in situ hybridization and meets 1 of the following risk criteria:

Medium-risk disease, defined by 1 of the following criteria:

Have had or are planning to have the following invasive procedures:

Inclusion Criteria:\n\n        Subjects must meet all of the following inclusion criteria to be eligible for enrollment\n        into the Intensive and Non Intensive study (unless where indicated):\n\n          1. Subjects with untreated AML according to the World Health Organization (WHO) 2016\n             Classification2, including those with:\n\n               -  AML arising from MDS or another antecedent hematologic disease (AHD).\n\n               -  AML after previous cytotoxic therapy or radiation (secondary AML).\n\n          2. 18 years of age (In Japan, 20 years of age).\n\n          3. Adequate Organ Function as defined by the following:\n\n               -  Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) 3\n                  x upper limit of normal (ULN), excluding subjects with liver function\n                  abnormalities due to underlying malignancy.\n\n               -  Total serum bilirubin 2 x ULN (except subjects with documented Gilbert's\n                  syndrome).\n\n               -  Estimated creatinine clearance 30 mL/min as calculated using the standard method\n                  for the institution.\n\n          4. QTc interval 470 msec using the Fridericia correction (QTcF).\n\n          5. All anti cancer treatments (unless specified) should be discontinued 2 weeks from\n             study entry, for example: targeted chemotherapy, radiotherapy, investigational agents,\n             hormones, anagrelide or cytokines.\n\n               -  For control of rapidly progressing leukemia, all trans retinoic acid (ATRA),\n                  hydroxyurea, and/or leukopheresis may be used before and for up to 1 week after\n                  the first dose of glasdegib.\n\n          6. Serum or urine pregnancy test (for female subjects of childbearing potential) with a\n             minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin\n             (hCG) negative at screening.\n\n          7. Male and female subjects of childbearing potential and at risk for pregnancy must\n             agree to use at least one highly effective method of contraception throughout the\n             study and for 180 days after the last dose of azacitidine, cytarabine, or\n             daunorubicin; and the last dose of glasdegib or placebo, whichever occurs later.\n\n          8. Female subjects of non childbearing potential must meet at least 1 of the following\n             criteria:\n\n               1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;\n\n               2. Have medically confirmed ovarian failure; or\n\n               3. Achieved postmenopausal status, defined as follows: cessation of regular menses\n                  for at least 12 consecutive months with no alternative pathological or\n                  physiological cause; status may be confirmed by having a serum follicle\n                  stimulating hormone (FSH) level confirming the postmenopausal state.\n\n             All other female subjects (including female subjects with tubal ligations) are\n             considered to be of childbearing potential.\n\n          9. Consent to a saliva sample collection for a germline comparator, unless prohibited by\n             local regulations or ethics committee (EC) decision.\n\n         10. Evidence of a personally signed and dated informed consent document indicating that\n             the patient has been informed of all pertinent aspects of the study.\n\n         11. Subjects who are willing and able to comply with the study scheduled visits, treatment\n             plans, laboratory tests and other procedures (including bone marrow [BM] assessments).\n\n        Exclusion Criteria:\n\n        Subjects with any of the following characteristics/conditions will not be included in the\n        study:\n\n          1. Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016\n             classification).\n\n          2. AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.\n\n               -  Complex genetics may include t(9;22) cytogenetic translocation.\n\n          3. Subjects with known active CNS leukemia.\n\n          4. Participation in other clinical studies involving other investigational drug(s)\n             (Phases 1 4) within 4 weeks prior study entry and/or during study participation.\n\n          5. Subjects known to be refractory to platelet or packed red cell transfusions per\n             Institutional Guidelines, or a patient who refuses blood product support.\n\n          6. Subjects with another active malignancy on treatment with the exception of basal cell\n             carcinoma, non melanoma skin cancer, cervical carcinoma in situ. Other prior or\n             concurrent malignancies will be considered on a case by case basis.\n\n          7. Any one of the following ongoing or in the previous 6 months: myocardial infarction,\n             congenital long QT syndrome, Torsades de pointes, symptomatic arrhythmias (including\n             sustained ventricular tachyarrhythmia), right or left bundle branch block and\n             bifascicular block, unstable angina, coronary/peripheral artery bypass graft,\n             symptomatic congestive heart failure (CHF New York Heart Association class III or IV),\n             cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism;\n             as well as bradycardia defined as <50 bpms.\n\n          8. Subjects with an active, life threatening or clinically significant uncontrolled\n             systemic infection not related to AML.\n\n          9. Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the\n             Intensive Chemotherapy Study only.\n\n         10. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the\n             Intensive Chemotherapy Study only.\n\n         11. Known malabsorption syndrome or other condition that may significantly impair\n             absorption of study medication in the investigator's judgment (eg, gastrectomy, lap\n             band, Crohn's disease) and inability or unwillingness to swallow tablets or capsules.\n\n         12. Current use or anticipated requirement for drugs that are known strong CYP3A4/5\n             inducers.\n\n         13. Concurrent administration of herbal preparations.\n\n         14. Major surgery or radiation within 4 weeks of starting study treatment.\n\n         15. Documented or suspected hypersensitivity to any one of the following:\n\n               -  For subjects assigned to intensive chemotherapy, documented or suspected\n                  hypersensitivity to cytarabine (not including drug fever or exanthema, including\n                  known cerebellar side effects) or daunorubicin.\n\n               -  For subjects assigned to non intensive chemotherapy, documented or suspected\n                  hypersensitivity to azacitidine or mannitol.\n\n         16. Known active drug or alcohol abuse.\n\n         17. Other acute or chronic medical or psychiatric condition including recent (within the\n             past year) or active suicidal ideation or behavior or laboratory abnormality that may\n             increase the risk associated with study participation or investigational product\n             administration or may interfere with the interpretation of study results and, in the\n             judgment of the investigator, would make the subject inappropriate for entry into this\n             study.\n\n         18. Pregnant females or breastfeeding female subjects.\n\n         19. Known recent or active suicidal ideation or behavior.\n\n         20. Investigator site staff members directly involved in the conduct of the study and\n             their family members, site staff members otherwise supervised by the investigator, or\n             subjects who are Pfizer employees, including their family members, directly involved\n             in the conduct of the study.

Screening hematology values of the following:

Screening chemistry values of the following:

Has either of the following:

Blood counts performed within 4 weeks prior to study entry must meet the following criteria:

are in relapse following an initial response and no more than 1 prior salvage therapy

Subjects must satisfy the following criteria to be enrolled in the study:

The presence of any of the following will exclude a subject from enrollment:

Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken:

Unresolved immune-related adverse events following prior biological therapy. Subjects with asymptomatic endocrinopathy may enroll.

Patients must have the following minimum wash-out from previous treatments:

Radiographic demonstration of disease progression following prior therapy

interval of ? 3 months following radiotherapy + TMZ;

If subjects have not passed an interval of at least 6 months, they may still be eligible if they meet the following criteria: convincing histologic evidence of disease recurrence which is not thought to predominantly represent radionecrosis, standard focal external beam radiation therapy (EBRT) treatment with acceptable doses to tumor and normal tissue which suggest re-irradiation is feasible; these cases of early recurrence must be reviewed and approved by the study PI for enrollment into the trial

Use of a combination of any two of the following (a+b or a+c, or b+c):

Current treatment with the following antiarrythmic drugs: flecainide, moricizine or propafenone

Patients with either of the following diagnoses:

Any of the following conditions:

Completed the following investigations

Must meet following requirements:

Female patients are eligible for the study if they meet the following criteria:

Patients must satisfy 1 of the following criteria for prior therapy:

Patients with any of the following adverse events at the time of enrollment are not eligible:\r\n*Grade ? 3 hyponatremia (serum Na ? 130 mmol/L)

THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: PDX data are non-informative.

THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Tumors do not engraft in the mice or do not respond to any of the selected agents.

THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: In Cohort 2, if disease progression occurs before Part 1 data are available, then they will be transferred to Cohort 1.

THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Any other exclusion criteria set forth by individual treatment protocol of the active clinical trial(s) through which patients are going to be treated.

Previous retreatment with cetuximab following progression on initial course of cetuximab therapy

Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide

Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration

Specifically, for participants in Cohorts A3 and A4: Treatment naïve participants unfit for induction chemotherapy for AML as defined by the following: Age >= 70 or age 65 to 69 years with at least one of the following: ECOG performance status of 2, Intermediate I/II or adverse risk cytogenetic and molecular alterations per ELN 2010 guidelines or secondary AML, or other comorbidity judged incompatible with intensive chemotherapy

Subject has air leak present on at least the 5th day following origination.

Must be willing to implement contraception throughout study and for the 4 weeks following last viral administration

Have had an R0/R1 resection of PDA following neoadjuvant chemotherapy

Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as ‘non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide

Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment:

Disease progression following radiation and TMZ

Severe CD as defined by one of the following:\r\n* CDAI >= 250\r\n* Need for total parenteral nutrition to maintain weight\r\n* Recurrent intestinal inflammation caused by CD following surgical resection

Patients must be enrolled within 56 weeks following completion of therapy

Patients who are initially rendered NED or have MRD following standard therapy but exhibit disease progression prior to initiation of vaccination

Patients with other cardiac diseases may be excluded at the discretion of the principal investigator (PI) following consultation with cardiology consultants

Patients must have at least one “target” lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Disease-related: meeting one of the following diagnosis

Therapeutic anticoagulation is not contraindicated, but for those patients on therapeutic anticoagulation, alteration in coagulation parameters is expected following initiation of dasatinib; for patients on therapeutic anticoagulation, coagulation parameters should be assessed weekly for the first cycle following initiation of dasatinib, weekly for the first cycle following a dose reduction, and weekly for a minimum of two weeks after stopping dasatinib

Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Subjects with central nervous system (CNS) (or leptomeningeal) infiltration by AML may be considered for treatment at the Investigator’s discretion and following discussion with the Principle Investigator; all neurologic deficits must be noted prior to enrollment on study

Residual areas of limited disease should receive radiotherapy following and not prior to transplantation

At least one of the following indications for treatment:

For subjects with INI1-negative tumors only - have the following test results available:

Patient must have clinical complete response or partial response following completion of chemotherapy course.

Subjects must satisfy the following criteria to be enrolled in the study:

The presence of any of the following will exclude a subject from enrollment:

The presence of any of the following will exclude a subject from enrollment into the Induction and Maintenance parts of the study (except if specified at study entry only):

Subjects with steroid-refractory acute GVHD, defined as any of the following:

For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.

Pathologically confirmed as triple negative, source documented, defined as both of the following:

The following medications are excluded:

The following drugs must be stopped > 1 week prior to CTL019 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non-pegylated)

Subject participating in studies involving approved drug or device will be enrolled only following a mutual consideration of the investigator together with the Sponsor.

Inclusion Criteria:\n\n          1. Written informed consent and any locally-required authorization (eg, Health Insurance\n             Portability and Accountability Act in the US, EU Data Privacy Directive in the EU)\n             obtained from the patient prior to performing any protocol-related procedures,\n             including pre-screening and screening evaluations\n\n          2. Age ?18 years at time of study entry\n\n          3. Histological or cytological confirmation of locally advanced (stage IIIB) or\n             metastatic (stage IV) solid tumours refractory to standard therapy or for which no\n             standard therapy exists\n\n          4. World Health Organisation Eastern Cooperative Oncology Group (ECOG) performance status\n             0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12\n             weeks\n\n          5. At least 1 lesion, not previously irradiated, that can be accurately measured at\n             baseline as ?10 mm in the longest diameter (except lymph nodes which must have short\n             axis ?15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and\n             which is suitable for accurate repeated assessment as per Response Evaluation Criteria\n             in Solid Tumours (RECIST criteria v1.1)\n\n          6. Female patients and males with partners of childbearing potential should be using\n             highly effective contraceptive measures. Females should not be breastfeeding 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 1 of the criteria\n             below at screening.\n\n               -  Postmenopausal defined as aged more than 50 years and amenorrhoeic for at least\n                  12 months following cessation of all exogenous hormonal treatments\n\n               -  Women <50 years old would be considered postmenopausal if they have been\n                  amenorrheic for the past 12 months or more following cessation of exogenous\n                  hormonal treatments. The levels of luteinising hormone (LH) and follicle\n                  stimulating hormone (FSH) must also be in the postmenopausal range (as per the\n                  institution)\n\n               -  Documentation of irreversible surgical sterilisation by hysterectomy and / or\n                  bilateral oophorectomy and/or bilateral salpingectomy but not tubal ligation\n\n          7. Male patients should be willing to use barrier contraception ie, condoms plus\n             spermicide\n\n          8. Mandatory provision of tumour tissue sample available at study entry for exploratory\n             biomarker research. Cytology samples for this exploratory biomarker research will not\n             be acceptable\n\n          9. Patients must have mCRC and, if MSI status is known, non-high MSI status. MSI status\n             will be evaluated based on previous results of local MSI testing, if available.\n             Patients with known MSI-high status will be excluded; patients with MSS, MSI-low, or\n             unknown MSI status may be enrolled\n\n        Exclusion Criteria:\n\n        Patients must not enter the study if any of the following exclusion criteria are fulfilled\n\n          1. Previous enrolment in the present study\n\n          2. Treatment with any of the following:\n\n               -  Cytotoxic chemotherapy or other anticancer drugs within 28 days of the 1st dose\n                  of study treatment or any investigational agents within 5 half-lives of the\n                  product\n\n               -  MEDI4736 or selumetinib in the present study (ie, dosing with MEDI4736 or\n                  selumetinib previously initiated in this study)\n\n               -  Major surgical procedure, (excluding placement of vascular access) or significant\n                  traumatic injury within 4 weeks of the 1st dose of study treatment, or have an\n                  anticipated need for major surgery during the study\n\n               -  Palliative radiotherapy with a wide field of radiation within 4 weeks or\n                  radiotherapy with a limited field of radiation for palliation within 2 weeks of\n                  the 1st dose of study treatment\n\n               -  Prior exposure to immune-mediated therapy, including, but not limited to, other\n                  anti-CTLA- 4 (Cytotoxic T-lymphocyte antigen-4), anti-PD-1 (Programmed cell death\n                  1), anti-PD-L1 (Programmed cell death ligand 1), or anti-PD-L2 (Programmed cell\n                  death ligand 2) antibodies, including therapeutic anticancer vaccines\n\n               -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP\n\n               -  Concurrent enrolment in another clinical study, unless it is an observational\n                  (non-interventional) clinical study or during the follow-up period of an\n                  interventional study\n\n          3. Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology\n             Criteria for Adverse Events) Grade ?2 from previous anticancer therapy with the\n             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion\n             criteria\n\n               -  Patients with Grade ?2 neuropathy will be evaluated on a case-by-case basis and\n                  may be included after consultation with the medical monitor\n\n               -  Patients with irreversible toxicity not reasonably expected to be exacerbated by\n                  treatment with selumetinib, MEDI4736 or tremelimumab may be included after\n                  consultation with the medical monitor\n\n          4. History of leptomeningeal carcinomatosis and brain metastases or spinal cord\n             compression. Patients with suspected brain metastases at screening should have a CT /\n             MRI of the brain prior to study entry\n\n          5. Active or prior documented autoimmune or inflammatory disorders (including\n             inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the\n             exception of diverticulosis], celiac disease, irritable bowel disease, or other\n             serious GI (Gastrointestinal) chronic conditions associated with diarrhoea, systemic\n             lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [eg, granulomatosis\n             with polyangiitis, Graves' disease; rheumatoid arthritis, hypophysitis, uveitis])\n             within the past 3 years prior to the start of treatment. The following are exceptions\n             to this criterion:\n\n               -  Patients with vitiligo or alopecia\n\n               -  Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone\n                  replacement or psoriasis not requiring systemic treatment\n\n          6. History of active primary immunodeficiency\n\n          7. Current or prior use of immunosuppressive medication within 14 days before the 1st\n             dose of MEDI4736. The following are exceptions to this criterion:\n\n               -  Intranasal, inhaled, topical steroids, or local steroid injections (eg,\n                  intra-articular injection)\n\n               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of\n                  prednisone or its equivalent\n\n               -  Steroids as premedication for hypersensitivity reactions (eg, CT scan\n                  premedication)\n\n          8. As judged by the investigator, any evidence of severe or uncontrolled systemic\n             diseases, including uncontrolled hypertension, renal transplant, active bleeding\n             diatheses, which in the investigator's opinion makes it undesirable for the patient to\n             participate in the study or which would jeopardise compliance with the protocol or\n             active infection including hepatitis B surface antigen (HBsAg), hepatitis C virus\n             (HCV) antibody or human immunodeficiency virus (HIV) or known history of clinical\n             diagnosis of tuberculosis\n\n          9. Screening for chronic conditions is not required\n\n         10. Any of the following cardiac criteria:\n\n               -  Any factors that increase the risk of QT(ECG interval measured from the onset of\n                  the QRS complex to the end of the T wave) interval corrected for heart rate (QTc)\n                  prolongation or risk of arrhythmic events (eg, heart failure, hypokalaemia,\n                  congenital long QT syndrome, family history of long QT syndrome or unexplained\n                  sudden death under 40 years of age) or mean QTc >470 msec\n\n               -  Uncontrolled hypertension (eg, BP ?150/95 mmHg despite medical therapy)\n\n               -  Acute coronary syndrome within 6 months prior to starting treatment\n\n               -  Angina Canadian Cardiovascular Society Grade II-IV (despite medical therapy)\n\n               -  Symptomatic heart failure (New York Heart Association II-IV)\n\n               -  Prior or current cardiomyopathy\n\n               -  Baseline LVEF (Left ventricular ejection fraction) <55% measured by\n                  echocardiography or MUGA. Appropriate correction to be used if a MUGA is\n                  performed.\n\n               -  Atrial fibrillation with a ventricular rate >100 beats per minute at rest\n\n               -  Severe valvular heart disease\n\n         11. Any of the following ophthalmic criteria:\n\n               -  Current or past history of central serous retinopathy, detachment of retinal\n                  pigmented epithelium, or retinal vein occlusion\n\n               -  Intraocular pressure (IOP) >21 mmHg\n\n               -  Uncontrolled glaucoma (irrespective of IOP)\n\n         12. Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following laboratory values:\n\n               -  Absolute neutrophil count <1.5 x 109/L\n\n               -  Platelet count <100 x 109/L\n\n               -  Haemoglobin <90 g/L\n\n               -  Alanine aminotransferase >2.5 x ULN (upper limit of normal) if no demonstrable\n                  liver metastases or >5 times ULN in the presence of liver metastases\n\n               -  Aspartate aminotransferase >2.5 x ULN if no demonstrable liver metastases or >5\n                  times ULN in the presence of liver metastases\n\n               -  Serum bilirubin ?1.5 x ULN. This will not apply to patients with confirmed\n                  Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia [predominantly\n                  unconjugated bilirubin] in the absence of evidence of haemolysis or hepatic\n                  pathology), who will be allowed in consultation with their physician\n\n               -  Creatinine clearance <50 mL/min (calculated by Cockcroft and Gault equation).\n                  Confirmation of creatinine clearance is only required when creatinine is >1.5\n                  times ULN\n\n         13. Refractory nausea and vomiting, chronic GI diseases, inability to swallow the\n             formulated product or previous significant bowel resection that would preclude\n             adequate absorption of selumetinib\n\n         14. History of hypersensitivity to active or inactive excipients of MEDI4736 or\n             selumetinib or drugs with a similar chemical structure or class to MEDI4736 or\n             selumetinib\n\n         15. 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         16. Involvement in the planning and conduct of the study (applies to both AZ staff or\n             staff at the study site)\n\n         17. Previous allogeneic bone marrow transplant\n\n         18. Body weight <30 kg

Active disease meeting ? 1 of the following IWCLL 2008 criteria for requiring treatment

Active disease meeting ? 1 of the following IWCLL 2008 criteria for requiring treatment.

The following medications are excluded:

The patient must meet one of the following (a) or (b) or (c):

The patient must meet one of the following (a) or (b) or (c):

Biopsy-proven diagnosis of primary systemic light chain amyloidosis (AL amyloidosis) according to the following standard criteria:

Treatment with any of the following:

Male patients must use a condom from the time of the first administration of ONO-7475 until 4 months following administration of the last dose.

Achieved less than a partial response (<PR) following at least 4 cycles and are without evidence of progression disease (PD). OR

Disease progression following an initial confirmed response of MR or better to the combination (according to IMWG response criteria).

Inclusion Criteria:\n\n        Patients must meet all of the following inclusion criteria in order to be entered into the\n        study:\n\n          1. Age 18 or older\n\n          2. Patient has signed informed consent\n\n          3. Patient must have a diagnosis of hepatocellular cancer confirmed by at least one of\n             the following:\n\n        i. Histological confirmation ii. Magnetic resonance imaging (MRI) result with early\n        enhancement and delayed enhancement washout of at least one solid liver lesion > 1 cm.\n        Patient must also have evidence of cirrhosis or have chronic hepatitis B.\n\n        iii. Contrast enhanced computed tomography (CT) with early enhancement and delayed\n        enhancement washout of at least one solid liver lesion > 1cm. Patient must also have\n        evidence of cirrhosis or have chronic hepatitis B.\n\n        d. Patient must not be suitable for treatment by resection or percutaneous ablation at time\n        of study entry.\n\n        Patients not suitable for ablation due to lesion location may be enrolled\n\n        e. Patient MUST meet at least ONE of the following criteria:\n\n        i. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1\n\n        f. Patient has a life expectancy of at least 6 months\n\n        g. Absence of occlusive thrombus to the main portal trunk\n\n        Exclusion Criteria:\n\n        If patients meet any of the following criteria they may not be entered into the study:\n\n          1. Current or previous treatment with chemo- or radiation therapy or sorafenib\n\n          2. Previous treatment with any form of transarterial embolization for HCC\n\n          3. Patients with current or history of any other cancer except non-melanomatous skin\n             cancer\n\n          4. Female patients who are pregnant, breastfeeding, or premenopausal and not using an\n             effective method of contraceptive\n\n          5. Performance status ECOG > 2\n\n          6. Child-Pugh scores >7\n\n          7. Active gastrointestinal bleeding\n\n          8. Evidence of uncorrectable bleeding diathesis\n\n          9. Extra-hepatic spread of the HCC\n\n         10. Total Bilirubin > 3 mg/dL\n\n         11. >50% tumor involvement of the liver\n\n         12. Infiltrative or diffuse HCC\n\n         13. Encephalopathy not adequately controlled medically\n\n         14. Presence of ascites not controlled medically\n\n         15. Presence of medically relevant localized or systemic infection, other than hepatitis\n             B, C, D, E or G\n\n         16. Any contraindication for MRI (eg. metallic implants)\n\n         17. Allergy to contrast media that cannot be managed with prophylaxis\n\n         18. Allergy to iodized oil\n\n         19. Any contraindication to arteriography\n\n         20. Any contraindication for doxorubicin administration, including the following:\n\n        i. White Blood Cell count (WBC) <3000 cells/mm?\n\n        ii. Absolute Neutrophil <1500 cells/mm?\n\n        iii. Cardiac ejection fraction <50%\n\n        iv. Other condition deemed exclusionary by physician\n\n        u. Any contraindication for hepatic embolization, including the following:\n\n        i. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior\n        to chemoembolization\n\n        ii. Hepatofugal blood flow\n\n        iii. Serum creatinine > 2mg/dL\n\n        iv. Uncorrectable impaired clotting\n\n          1. Platelet <50,000/mm?\n\n          2. International Normalized Ratio (INR) > 1.4\n\n          3. Activated Prothrombin Time (aPTT) less than 21 or greater than 40\n\n             v. AST > 5X upper limit of normal for lab\n\n             vi. ALT > 5X upper limit of normal for lab

Use of 5-alpha reductase inhibitors (5-ARIs) or hormone therapy within 3 months prior to the baseline visit. Baseline PSA must be established after a minimum of 3 months following 5-ARIs discontinuation. Additionally, use of 5-ARIs is not permitted following treatment during the study follow-up period.

Subjects must satisfy the following criteria to be enrolled into the study:

one or more of the following Myeloma-related organ dysfunction (at least one of the following);

Serum LDH > 2 x ULN (Upper limit of normal); 9. For Cohort B subject must be ? 65 years of age at the time of signing the informed consent form (ICF) and transplant non-eligible (TNE); excluding the subjects who meet the Cohort A criteria 10. For Cohort C subject must be after first autologous stem cell transplantation (ASCT) for NDMM and meet the following criteria:

The presence of any of the following will exclude a subject from enrollment:

Prior history of malignancies, other than MM, unless the subject has been free of the disease for ? 5 years with the exception of the following non-invasive malignancies:

The following medications are excluded:

Part 1 Dose Escalation subjects must meet 1 of the following criteria:

Part 2 Dose Expansion subjects must meet 1 of the following criteria:

Unidimensionally measurable disease; indicator lesions must not have been irradiated unless they have grown following radiation therapy

Diagnosis with confirmed histology of one or more of the following:

Relapsed following, or refractory to, previous ASCT

Male subjects must refrain from donating sperm starting at the planned first dose of investigational product (IP) until 30 days following the last dose of IP

Female partners of male subjects who are of childbearing potential must also adhere to one of the following:

3. Female subjects of childbearing potential1 may participate, providing they meet the following conditions:

Age ? 65 years at the time of signing the informed consent form (ICF). 11. Central confirmation of diagnosis of one of the following untreated AML as per WHO classification (Appendix I):

Use of any of the following within 28 days prior to the first dose of IP:

Indication for treatment consistent with IWCLL criteria, i.e. at least one of the following criteria should be met

Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:

Clinically quantifiable disease burden defined as at least one of the following:

Tissue Procurement Inclusion Criteria:\n\n        Patients 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 Ewing's Sarcoma Family of Tumors (ESFT).\n\n          2. Age ?2 years.\n\n          3. Estimated survival ? 6 months.\n\n          4. Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS).\n\n          5. Metastatic disease\n\n          6. Refractory or intolerant to at least 1 line of systemic chemotherapy.\n\n          7. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative\n             resection or thoracentesis) and expected availability of a cumulative mass of ~10-30\n             grams tissue (\golf-ball\ size) or pleural fluid estimated volume ? 500mL (must be\n             primary tap) for immunotherapy manufacture.\n\n          8. 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          9. Ability to understand and the willingness to sign a written informed consent document\n             for tissue harvest.\n\n        Tissue Procurement Exclusion Criteria:\n\n        Patients 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 history of allergies or sensitivities to gentamicin.\n\n          6. 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          7. Known HIV or chronic Hepatitis B or C infection.\n\n        Study Enrollment Inclusion Criteria:\n\n        Patients will be eligible for registration if they meet all of the following inclusion\n        criteria:\n\n          1. Successful manufacturing of at least 4 vials of Vigil.\n\n          2. Karnofsky performance status (PS) ?80%.\n\n          3. Estimated survival ? 6 months.\n\n          4. Normal organ and marrow function as defined below:\n\n             Absolute granulocyte count ?1,500/mm3 Absolute lymphocyte count ?400/mm3 Platelets\n             ?100,000/mm3 Total bilirubin ? institutional upper limit of normal AST(SGOT)/ALT(SGPT)\n             ?2x institutional upper limit of normal Creatinine <1.5 mg/dL\n\n          5. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated\n             with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or\n             symptoms must be recovered to CTCAE Grade 2 or better.\n\n          6. If female of childbearing potential, has a negative urine or serum pregnancy test. If\n             the urine test is positive or cannot be confirmed as negative, a negative serum test\n             will be required for study entry.\n\n          7. Ability to understand and the willingness to sign a written informed protocol specific\n             consent.\n\n        Study Enrollment Exclusion Criteria:\n\n        Measureable disease is not a requirement for enrollment onto the trial.\n\n        In addition to the procurement exclusion criteria, patients will NOT be eligible for study\n        registration and randomization if meeting any of the following criteria:\n\n          1. Any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start\n             of study therapy.\n\n          2. Live vaccine used for the prevention of infectious disease administered < 30 days\n             prior to the start of study therapy.\n\n          3. Post-surgery complication that in the opinion of the treating investigator would\n             interfere with the patient's study participation or make it not in the best interest\n             of the patient to participate.

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. Presumptive Stage IIIb, IIIc or IV high-grade papillary serous/clear cell/endometrioid\n             ovarian, fallopian tube or primary peritoneal cancer.\n\n          2. No chemotherapy prior or investigational agents prior to tissue acquisition for Vigil\n             manufacture.\n\n          3. No other malignancy (excluding surgically cured nonmelanoma carcinomas of the skin and\n             carcinoma in situ cervix) unless in remission for ? 2 years.\n\n          4. Anticipated availability of a cumulative mass of ~30 grams tissue (\golf-ball\ size or\n             approximately 3cm disease on CT scan) at time of diagnostic laparoscopy or primary\n             surgical debulking. Infiltrating lumen (bowel, fallopian tube, urethra) tissue should\n             not be used as Vigil immunotherapy material to minimize risk of bacterial\n             contamination.\n\n          5. ECOG performance status (PS) 0-2 prior to diagnostic laparoscopy or debulking\n             laparotomy.\n\n          6. No prior history of hypersensitivity reactions (HSR) with taxanes or platinums.\n\n          7. No prior history of allergies or sensitivities to gentamicin.\n\n          8. Female, 18 years of age or older.\n\n          9. Ability to understand and the willingness to sign a written informed consent document\n             for tissue harvest.\n\n        Subjects will be registered in this study if they meet all of the following inclusion\n        criteria:\n\n          1. Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous/clear\n             cell/endometrioid ovarian, fallopian tube or primary peritoneal.\n\n          2. Completion of primary surgical debulking including hysterectomy and bilateral salpingo\n             oophorectomy, and at least 5 but no more than 8 cycles of platinum / taxane adjuvant\n             chemotherapy or chemotherapy as per Category 1 recommendations of the NCCN guidelines,\n             including 5-8 cycles adjuvant intraperitoneal + intravenous (IP/IV) chemotherapy, or\n             5-8 cycles of intravenous chemotherapy divided and administered as neoadjuvant and\n             adjuvant therapy flanking primary debulking surgery.\n\n          3. Clinically defined complete response (cCR) following completion of primary surgical\n             debulking and eligible chemotherapy. cCR defined as no evidence of malignancy on chest\n             x-ray (CT scan is acceptable) and CT scan or MRI of the abdomen and pelvis, normal\n             physical examination, CA-125 antigen level ? 35 U/ml (assessed ? 2 weeks following\n             removal of catheter in subjects receiving intraperitoneal/intravenous chemotherapy)\n             and no findings on physical examination or symptoms suggestive of active cancer.\n\n          4. Subjects must have initiated adjuvant chemotherapy no more than 8 weeks following\n             primary debulking surgery.\n\n          5. Successful manufacturing of at least 4 doses (vials) of Vigil and placebo.\n\n          6. Recovered from all clinically relevant toxicities related to prior therapy (including\n             neuropathy ?Grade 2).\n\n          7. ECOG performance status (PS) 0-1.\n\n          8. Normal organ and marrow function as defined below: Absolute granulocyte count ?\n             1,500/mm^3, Absolute lymphocyte count ? 500/mm^3, Platelets ? 75,000/mm^3, Total\n             bilirubin ? 2 mg/dL, AST(SGOT)/ALT(SGPT)? 2x institutional upper limit of normal,\n             Creatinine < 1.5 mg/dL\n\n          9. Ability to understand and the willingness to sign a written informed protocol specific\n             consent.\n\n        Exclusion Criteria:\n\n        Subjects will be excluded from this study if they meet any of the following criteria (at\n        the time of tissue procurement or at randomization):\n\n          1. Surgery involving general anesthesia, radiotherapy, immunotherapy, or investigational\n             agents within 4 weeks prior to randomization.\n\n          2. Histologically confirmed papillary serous adenocarcinoma of the uterus or disease\n             involving myometrium/endometrium.\n\n          3. Systemic immunosuppressive therapy within 14 days of randomization.\n\n          4. Subjects requiring chronic steroid or immunosuppressive regimens are excluded except\n             inhaled / intranasal steroids and short term systemic steroids <30 days duration and\n             ?0.25 mg/kg prednisone-equivalent per day are allowed.\n\n          5. Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or\n             hemodynamically significant atrial arrhythmia, or cardiovascular disease such as\n             stroke or myocardial infarction (current or within the past 6 months).\n\n          6. Psychiatric illness/social situations that would limit compliance with study\n             requirements.\n\n          7. Subjects with history of brain metastases.\n\n          8. Subjects with known HIV or chronic Hepatitis B or C infection.\n\n          9. Prior solid organ or bone marrow transplant.\n\n         10. History of or active autoimmune disease (e.g., autoimmune neutropenia,\n             thrombocytopenia, or hemolytic anemia, systemic lupus erythematosus, Sjogren's\n             syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease,\n             Hashimoto's thyroiditis, or Graves disease). Persons with vitiligo are not excluded.\n             Diabetics are not excluded if the condition is well controlled.

Prior treatment with the following:

Blood counts performed within 28 days prior to randomization must meet the following criteria:

History of erythema multiforme, Grade >= 3 rash, or blistering following prior treatment with immunomodulatory derivatives such as thalidomide and lenalidomide

Positive serology for HTLV 1 or 2. Furthermore and prior to lymphodepleting chemotherapy, a subject meeting the following criteria is not eligible for participation in the study:

Subjects must satisfy the following criteria to be enrolled in the study:

Documented diagnosis of any of the following:

Females of childbearing potential (FCBP) may participate, providing the subject meets the following conditions:

Documented progressive metastatic CRPC will be based on at least one of the following criteria:

Patients with prior radiation therapy are eligible if they meet the following criteria:

Patients must have progressive mCRPC defined by meeting at least one of the following criteria:

Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL)

Must have progressed following or have been unable to tolerate at least one prior anthracycline or alkylating agent containing regimen (with or without anti-CD20).

For Phase 2, subjects with the following tumor types who meet protocol-defined criteria: advanced or metastatic NSCLC, melanoma, urothelial carcinoma, SCCHN, SCLC, and CRC.

Post-, pre- or peri-menopausal women considered to be in the post?menopausal state as defined by one of the following:

Subjects may be eligible to receive MK-3475 in the second course phase of this study if the study remains open and the subject meets the following conditions:

Patients must have at least one “target” lesion to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Have confirmed diagnosis of MPM with the following characteristics:

Have any history of the following:

Prior anticancer or investigational drug treatment within the following windows:

Patients must have at least one \target lesion\ to be used to assess response on this protocol as defined by RECIST 1.1 (Section 8.1). Tumors within a previously irradiated field will be designated as \non-target\ lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.

Patients with any of the following risk factors:

Patients must have progressive disease defined as at least one of the following:

Previous or concomitant malignancies at any other site with the exception of the following:

Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which includes at least one of the following criteria:\r\n* Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)\r\n* Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly\r\n* Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy\r\n* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy\r\n* Constitutional symptoms, which include any of the following:\r\n** Unintentional weight loss of 10% or more within 6 months\r\n** Significant fatigue\r\n** Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection\r\n** Night sweats > 1 month without evidence of infection

Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide

At least one measurable target lesion according to mRECIST meeting the following criteria:

Subjects with any of the following MEDICATIONS within 4 weeks prior to randomization:

Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined at least one of the following:

Baseline serum PSA value performed with an Food and Drug Administration (FDA)-approved assay (e.g., Abbott, Hybritech) within 60 days prior to registration\r\n* Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride

History of prior therapy that satisfies one of the following criteria:

A female subjects is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:

Subject has any of the following comorbidities:

Relapsed or refractory B-precursor ALL defined as one of the following:

Tumors within previous radiated field will be designated “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Are receiving chronic therapy with any of the following medications within 7 days prior to enrollment:

Relapsed or progressed following endocrine therapy.

Inclusion Criteria:\n\n        A subject will be eligible for inclusion in this study only if all of the following\n        criteria are met:\n\n          1. Male or female subject is between 18 and 65 years of age at the time of signing the\n             Informed Consent Form (ICF).\n\n          2. Subject has definitive histologically or cytologically confirmed metastatic pancreatic\n             adenocarcinoma.\n\n          3. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.\n\n          4. Subject has one or more tumors measurable by CT scan (or (MRI), if allergic to CT\n             contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST)\n             1.1.\n\n          5. Subject has the following blood counts / Hemoglobin (Hgb) at screening:\n\n               -  Absolute neutrophil count (ANC) ? 1.5 × 10^9/L;\n\n               -  Platelet count ? 100,000/mm3 (100 × 10^9/L);\n\n               -  Hgb ? LLN or 10 g/dL.\n\n          6. Subject has the following blood chemistry levels at screening:\n\n               -  AST (SGOT), ALT (SGPT) ? 2.5 x upper limit of normal range (ULN); if hepatic\n                  metastases present ? 5.0 x ULN\n\n               -  Total bilirubin ? 1.5 X ULN\n\n               -  Creatinine clearance ? 60 mL/min (by Cockroft-Gault)\n\n               -  Albumin ? 3.5 grams/dL7.\n\n          7. Females of childbearing potential (FOCBP) [defined as a sexually mature woman who (1)\n             have not undergone hysterectomy (the surgical removal of the uterus) or bilateral\n             oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally\n             postmenopausal for at least 24 consecutive months (ie, has had menses at any time\n             during the preceding 24 consecutive months)] must:\n\n               -  Have a negative pregnancy test (?-human chorionic gonadotropin [? -hCG]) as\n                  verified by the study doctor within 72 hours prior to starting study therapy\n\n               -  Commit to complete abstinence from heterosexual contact, or agree to use medical\n                  doctor-approved contraception throughout the study without interruption; while\n                  receiving study medication and for at least 6 months following last dose of study\n                  IP.\n\n          8. Males must practice complete abstinence or agree to use a condom (even if he has\n             undergone a successful vasectomy) during sexual contact with a pregnant female or a\n             female of childbearing potential while participating in the study, during dose\n             interruptions and for at least 6 months following last dose of study IP.\n\n          9. Subject has no clinically significant abnormalities in urinalysis results at baseline.\n\n         10. Subject is able to adhere to the study visit schedule and other protocol requirements.\n\n         11. Subject understands the nature of the study, and has agreed to participate in the\n             study, and has voluntarily signed the ICF prior to participation in any study-related\n             activities.\n\n         12. Subject must consent to provide protocol-mandated tumor and blood samples for\n             molecular analysis.\n\n         13. Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements\n\n        Exclusion Criteria:\n\n        A subject will not be eligible for inclusion in this study if any of the following criteria\n        apply:\n\n          1. Subject has received previous systemic chemotherapy or investigational therapy (other\n             than that as a radiosensitizer concomitant with radiotherapy) for the treatment of\n             pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy.\n\n          2. Subject has known brain metastases unless previously treated and controlled for a\n             minimum of 2 weeks prior to enrollment. Subject is not receiving corticosteroids with\n             no evidence of cerebral edema.\n\n          3. Pre-existing peripheral neuropathy > Grade 1\n\n          4. Subject with unstable stent.\n\n          5. History of malignancy in the last 3 years. Subjects with prior history of in situ\n             cancer or basal or squamous cell skin cancer are eligible. Subjects with other\n             malignancies are eligible if they were cured by surgery alone or surgery plus\n             radiotherapy and have been continuously disease-free for at least 3 years.\n\n          6. Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring\n             systemic therapy , defined as ongoing signs/symptoms related to the infection without\n             improvement despite appropriate antibiotics, antiviral therapy, and/or other\n             treatment.\n\n          7. Subject has known historical or active infection with human immunodeficiency virus\n             (HIV), hepatitis B, or hepatitis C or subject receiving immunosuppressive or\n             myelosuppressive medications that would, in the opinion of the Investigator, increase\n             the risk of serious neutropenic complications.\n\n          8. Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done\n             to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to\n             Day 1 of treatment in this study or surgical wound has not fully healed.\n\n          9. Subject has a history of allergy or hypersensitivity to any of the IP or any of their\n             excipients, or the subject exhibits any of the events outlined in the\n             Contraindications or Special Warnings and Precautions sections for and of the\n             products' Summary of Product Characteristics or Prescribing Information.\n\n         10. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).\n\n         11. Subject with a history of interstitial lung disease, history of slowly progressive\n             dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis,\n             pulmonary hypersensitivity pneumonitis or multiple allergies that in the opinion of\n             the Investigator may put them at increased risk of interstitial pneumonitis.\n\n         12. Subject with high cardiovascular risk, including, but not limited to:\n\n               -  uncontrolled hypertension\n\n               -  unstable angina\n\n               -  diagnosis of ischemic heart disease\n\n               -  heart disease of New York Heart Association functional classification ? 3 (see\n                  Appendix C)\n\n               -  prior history of hemorrhagic or thrombolytic stroke\n\n               -  prior exposure to anthracycline\n\n               -  history of peripheral artery disease (eg, claudication, Leo Buerger's disease)\n\n               -  any of the following within the prior 6 months\n\n               -  coronary stenting\n\n               -  myocardial infarction\n\n               -  coronary bypass surgery\n\n         13. Recent history of clinically significant hemoptysis.\n\n         14. Pregnant and nursing (lactating) women.\n\n         15. Any significant medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the subject from participating in the study.\n\n         16. Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n         17. Subject has any condition that confounds the ability to interpret data from the study.

Subject has used any of the following within 28 days before the Day 1 visit:

Patients with measurable disease must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Subjects must not donate blood while on study and for at least 90 days following the last MEDI4736 treatment.

Relapsed or refractory CLL patients must meet the following requirements:\r\n* Received at least 1 prior therapy\r\n* Require treatment in the opinion of the investigator\r\n* Relapsed patients must have developed progressive disease following a response to a prior therapy\r\n* Refractory patients must have failed to respond or relapsed within 6 months to the last prior therapy

Histologically confirmed AML (defined using World Health Organization [WHO] criteria) with one of the following:\r\n* Primary refractory disease following =< 2 cycles of induction chemotherapy, or\r\n* First relapse with no prior unsuccessful salvage chemotherapy, or\r\n* Relapsed or refractory to hypomethylating agent, defined as a lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator

A survivor of prior cancer is eligible provided that ALL of the following criteria are met and documented:

Symptomatic disease because of active PVNS or GCT-TS, defined as one or more of the following:

Adequate coagulation functioning within 28 days prior to registration for protocol therapy defined by either of the following criteria:

Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as bevacizumab

Disease progression following therapy with erlotinib, afatinib, or gefitinib

Treatment with any of the following:

No evidence of Calcium, Renal, Anemia, and Bone (CRAB) criteria or new criteria of active MM which including the following:\r\n* Increased calcium levels: corrected serum calcium > 0.25 mmol/L (> 1 mg/dL) above the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)\r\n* Renal insufficiency (attributable to myeloma)\r\n* Anemia (hemoglobin [Hgb] 2 g/dL below the lower limit of normal or < 10 g/dL)\r\n* Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\r\n* No evidence of the following new criteria for active MM including the following:\r\n** Bone marrow plasma cells > 60%, serum involved/uninvolved free light-chain (FLC) ratio >= 100, and MRI with more than one focal lesion\r\n* Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible

Tumors within a previously irradiated field will be designated as \non-target\ lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

No prior systemic therapy for RCC with the following exception:

Previously untreated subjects that meet ANY of the following criteria:\r\n* Subjects that refuse to be treated with chemotherapy based agents (this should be documented in the consent form)\r\n* Subjects that are not candidates for treatment with chemotherapy agents based on ANY of the following:\r\n** ECOG performance status >= 2\r\n** Advance age (>= 65 years)\r\n** Cumulative Illness Rating Scale (CIRS score) >= 6\r\n** Cytopenias\r\n*** Hemoglobin (Hb) =< 100 g/L (10 g/dL)\r\n*** Platelet count =< 100 x 10^9/L (100,000/uL)\r\n*** Absolute neutrophil count (ANC) =< 1.5 x 10^9/L (1,500/uL)

Subjects must meet the following criteria:

Multiple myeloma which has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.

Must meet one of the following two criteria:

Cholangiocarcinoma subjects must have progressed following gemcitabine-based regimen.

Patients have to meet one of the following criteria to be eligible:\r\n* Disease determined unresectable or entailing unacceptably morbid surgery based on 1 or more of the following characteristics:\r\n** Multifocal disease\r\n** Disease in which there is involvement or inadequate plane from: neurovascular bundle, bone, skin, or viscera\r\n** Large size in relationship to location OR multi-compartment involvement\r\n* Progression by radiographic imaging (10% increase in size by RECIST v1.1 within 6 months of registration)\r\n* Patients with symptomatic disease which meets the following criteria Brief Pain Inventory (BPI) score greater than or equal to 3 AND one of the following:\r\n** Inability to control pain with NSAIDs and considering addition of narcotics OR\r\n** > 30% increase in current use of narcotics OR\r\n** Addition of a new opioid narcotic

Baseline hematologic studies and chemistry profiles must meet the following criteria:

Inclusion Criteria:\n\n        Patients in both treatment groups must meet all of the following criteria to be considered\n        eligible to participate in the study:\n\n          -  Adult men or women, aged 18 years or older, with histologically-confirmed, metastatic\n             adenocarcinoma of the colon or rectum that is resistant to available treatment options\n\n          -  Radiographically documented evidence of disease progression.\n\n          -  Life expectancy of at least 6 weeks, in the investigator's opinion, at the time\n             disease progression is documented.\n\n          -  Considered surgical candidates on the basis of co-morbidity risks, number and sites of\n             metastases, and ability to withstand general anesthesia.\n\n          -  Able to provide written informed consent.\n\n        Patients in Group A must also meet all of the following additional criteria:\n\n          -  ECOG performance status score of 0, 1, or 2.\n\n          -  Adequate hematologic function, defined as follows:\n\n               1. absolute neutrophil count (ANC) ?1500 /mL\n\n               2. hemoglobin ?9 g/dL\n\n               3. platelets ?75,000 /mL\n\n          -  Adequate hepatic function, defined as follows:\n\n               1. bilirubin ?1.5 times the upper limit of normal (x ULN)\n\n               2. aspartate transaminase (AST) ?3 x ULN, or ?5 x ULN if liver metastases are\n                  present\n\n               3. alanine transaminase (ALT) ?3, x ULN, or ?5 x ULN if liver metastases are present\n\n          -  Adequate renal function, defined as creatinine ?2.0 mg/dL.\n\n          -  Adequate coagulation function, defined as follows:\n\n               1. International Normalized Ratio (INR) ?1.5 or between 2 and 3 if the patient is\n                  receiving anticoagulation\n\n               2. partial thromboplastin time (PTT) ?5 seconds above the ULN Note: Patients\n                  receiving full-dose anticoagulation therapy must be receiving a stable dose of\n                  oral anticoagulant therapy or low-molecular-weight heparin.\n\n          -  Clinically significant toxic effects of chemotherapy (excluding alopecia),\n             radiotherapy, hormonal therapy, or prior surgery must have resolved to Grade 1 or\n             better, with the exception of peripheral neuropathy, which must have resolved to Grade\n             2 or better.\n\n          -  Agrees to contraceptive use while on study if sexually active\n\n        Exclusion Criteria:\n\n        Patients in either treatment group who meet any of the following criteria will be excluded\n        from participating in the study:\n\n          -  Hepatic blood flow abnormalities, i.e., portal vein hypertension and thrombosis,\n             and/or a large volume of ascites.\n\n          -  Concurrent cancer of any other type, except skin cancers other than melanoma.\n\n          -  A positive test result for HIV or any hepatitis other than A at screening.\n\n          -  Considered by the investigator to be unsuitable for participation in the study\n\n        Patients in Group A who meet any of the following criteria will be excluded from\n        participating in the study:\n\n          -  Received FDA-approved chemotherapy within 3 weeks of Day 0, or bevacizumab (or similar\n             drugs) within 4 weeks of Day 0, or radiation therapy at any site within 4 weeks of Day\n             0\n\n          -  Investigational anticancer therapy within 4 weeks of Day 0\n\n          -  Positive reaction to the skin test for allergy to mouse antigen\n\n          -  History of hypersensitivity reaction that, in the opinion of the investigator, poses\n             an increased risk of an allergic reaction to the RENCA macrobeads, particularly any\n             known allergy to murine antigens or body tissues.\n\n          -  Ongoing or active infection, symptomatic congestive heart failure, unstable angina\n             pectoris, serious cardiac arrhythmias (with the exception of well controlled atrial\n             fibrillation), active bleeding, or psychiatric illness, or social situations that\n             could interfere with the patient's ability to participate in the study.

Adequate cardiac conduction by ECG without evidence of second- or third-degree atrioventricular block and meeting all of the following ECG criteria:

Prior history of malignancies, other than MM, unless the patient has been free of the disease for ? 3 years. Exceptions include the following:

Subject has disease progression by at least one of the following:

One of the following acceptable forms of contraception is required:

Treatment with any of the following:

Patient must have a histologically verified diagnosis of craniopharyngioma\r\n* Stratum 1: patients with progressive unresectable or recurrent craniopharyngiomas treated with surgery alone, who have not received radiation therapy; patients with unresectable craniopharyngiomas, (i.e. residual measurable disease following surgical resection) will be enrolled at the time of progression\r\n* Stratum 2: patients with progressive or recurrent craniopharyngiomas following radiation therapy; the patient must be at least 6 months post irradiation to be eligible

Patients must meet all of the following criteria to be enrolled in the study:

The presence of any of the following will exclude a patient from enrollment:

Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined as at least one of the following:

Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject is ? 18 years of age at the time of signing the informed consent form (ICF).\n\n          2. Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          3. Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n          4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.\n\n          5. Subjects must have a documented diagnosis of MM and measurable disease at enrollment.\n\n          6. Subjects must have the following laboratory values:\n\n               -  Absolute neutrophil count (ANC) ? 1.25 x 109/L without growth factor support for\n                  ? 7 days (? 14 days for pegfilgrastim).\n\n               -  Hemoglobin (Hgb) ? 8 g/dL.\n\n               -  Platelets (plt) ? 75 x 109/L without transfusion for ? 7 days (? 50 x 109/L for\n                  subjects with > 50% plasma cells in bone marrow).\n\n               -  Corrected serum calcium ? 13.5 mg/dL (? 3.4 mmol/L).\n\n               -  24-hr creatinine clearance (CrCl) ? 45 mL/min.\n\n               -  AST/SGOT and ALT/SGPT ? 3.0 x upper limit of normal (ULN).\n\n               -  Serum bilirubin ? 1.5 x ULN.\n\n               -  Uric acid ? 7.5 mg/dL (446 ?mol/L).\n\n               -  PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for\n                  subjects not receiving therapeutic anticoagulation).\n\n          7. Females of childbearing potential (FCBP) must:\n\n               1. Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after discontinuation of CC-92480. This applies even if\n                  the subject practices true abstinence* from heterosexual contact.\n\n               2. Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis and source documented) or agree to use, and be able\n                  to comply with, two reliable forms of contraception without interruption, 28 days\n                  prior to starting CC-92480, during the study therapy (including during dose\n                  interruptions), and for 28 days after discontinuation of study therapy.\n\n          8. Male subjects must:\n\n               1. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to\n                  use of a condom during sexual contact with a pregnant female or a female of\n                  childbearing potential while participating in the study (even during dose\n                  interruptions) and for at least 3 months following CC-92480 discontinuation, even\n                  if he has undergone a successful vasectomy.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Subject has a significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n          2. Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n          3. Subject has any condition that confounds the ability to interpret data from the study.\n\n          4. Subject has non- or oligosecretory multiple myeloma.\n\n          5. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.\n\n          6. Subject has documented, systemic light chain amyloidosis or Polyneuropathy,\n             Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS)\n             Syndrome.\n\n          7. Subject has immunoglobulin class M (IgM) myeloma.\n\n          8. Subject has a history of allogeneic bone marrow transplantation.\n\n          9. Subject is undergoing dialysis.\n\n         10. Subjects with peripheral neuropathy ? Grade 2.\n\n         11. Subjects with gastrointestinal disease that may significantly alter the absorption of\n             CC-92480.\n\n         12. Subject has impaired cardiac function or clinically significant cardiac disease,\n             including any of the following:\n\n               -  LVEF < 45% as determined by ECHO or MUGA scan at Screening.\n\n               -  Complete left bundle branch, bifascicular block or other clinically significant\n                  abnormal electrocardiographic (ECG) finding at Screening.\n\n               -  A prolongation of QT interval on Screening ECG; a history of or current risk\n                  factors for Torsades de Pointe; and concurrent administration of medications that\n                  prolong the QT/QTc interval.\n\n               -  Congestive heart failure (New York Heart Association Class III or IV).\n\n               -  Myocardial infarction ?6 months prior to starting CC-92480.\n\n               -  Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n                  of angina pectoris.\n\n         13. Concurrent administration of strong CYP3A modulators.\n\n         14. Subject had prior systemic myeloma treatment (approved or investigational) ? 5\n             half-lives or 4 weeks prior to starting CC-92480, whichever is shorter.\n\n         15. Subject had major surgery ? 2 weeks prior to starting CC-92480.\n\n         16. Subject is a pregnant or nursing female or intends to become pregnant during\n             participation in the study.\n\n         17. Subject has known human immunodeficiency virus (HIV) infection.\n\n         18. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.\n\n         19. Subject has a history of concurrent second cancer requiring ongoing systemic\n             treatment.\n\n         20. Subjects has a history of prior malignancy other than MM, unless the subject has been\n             free of disease for ?3 years except for the following noninvasive malignancies treated\n             with curative intent:\n\n         21. Subject has known or suspected hypersensitivity to the excipients contained in the\n             formulation of CC-92480 or dexamethasone.\n\n         22. Subject has undergone either of the following within 14 days of initiating CC-92480:\n\n               -  Plasmapheresis.\n\n               -  Radiation therapy other than local therapy for symptomatic relief of MM\n                  associated bone lesions.\n\n         23. Subject has received immunosuppressive medication within 14 days prior to the first\n             dose of CC-92480.

Progression following treatment with fluoropyrimidine/oxaliplatin/bevacizumab-regimen in the metastatic setting.

Participants who have had or are planning to have the following invasive procedures

Subjects should not have severe peritoneal metastases. The following criteria were applied:

Patients must be greater than 12 weeks following completion of chemoradiation or any additional radiation to reduce the chance of pseudoprogression

Patient must have one of the following:

Patients for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for high-dose therapy followed by stem-cell transplantation (HDT-SCT) for 1 or more of the following reasons:

Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:

Measurable disease (tumors within a previously irradiated field will be designated as \nontarget\ lesions unless progression is documented incontrovertibly either radiographically or pathologically; for clinicians relying on biopsy documentation of recurrence, this must be obtained to confirm persistence at least 90 days following completion of radiation therapy)

Participants must have achieved a complete or partial response per disease-appropriate imaging technique (to be determined by the study principal investigator) within 4 weeks of study entry following administration of chemotherapy

Diagnosis of one of the following:

Depending upon patient prior treatment the following apply:

Patients with \anaplastic\ features are eligible for this trial as defined by at least one of the following: a) any of the following metastatic presentations: exclusive visceral metastases, radiographically predominant lytic bone metastases identified by plain X-ray or CT scan, bulky (> 5 cm in longest dimension) lymphadenopathy or high-grade (Gleason > 8) tumor mass in the prostate/pelvis; b) low PSA (=< 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases; c) elevated serum lactate dehydrogenase (LDH) (>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (>= 2 x ULN) in the absence of other etiologies; d) short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy

Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Must be ? 18 years at the time of signing the informed consent form\n\n          2. Must understand and voluntarily sign an informed consent document prior to any\n             study-related assessments/procedures\n\n          3. Must be able to adhere to the study visit schedule and other protocol requirements\n\n          4. Must have documented diagnosis of relapsed or refractory multiple myeloma and have\n             measurable disease (serum M-protein ? 0.5 g/dL or urine M-protein ? 200 mg/24 hours)\n\n          5. Must have had at least 1 prior anti-myeloma regimen\n\n          6. Must have documented progression as per the International Myeloma Working Group\n             uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen\n\n          7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2\n\n          8. Females of childbearing potential (FCBP) must agree to utilize two reliable forms of\n             contraception simultaneously or practice complete abstinence from heterosexual contact\n             for at least 28 days before starting study drug, while participating in the study\n             (including dose interruptions), and for at least 28 days after study treatment\n             discontinuation, and must agree to regular pregnancy testing during this timeframe\n\n          9. Females must agree to abstain from breastfeeding during study participation and for 28\n             following discontinuation from study treatment\n\n         10. Males must agree to use a latex condom during any sexual contact with FCBP while\n             participating in the study and for 28 days following discontinuation from study\n             treatment, even if he has undergone a successful vasectomy\n\n         11. Males must also agree to refrain from donating semen or sperm while on pomalidomide\n             and for 28 days after discontinuation from study treatment\n\n         12. All subjects must agree to refrain from donating blood while on study drug and for 28\n             days after discontinuation from study treatment\n\n         13. All subjects must agree not to share medication\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Peripheral neuropathy ? Grade 2\n\n          2. Non-secretory multiple myeloma\n\n          3. Any of the following laboratory abnormalities:\n\n               -  Absolute neutrophil count (ANC) < 1,000/µL\n\n               -  Platelet count < 75,000/µL\n\n               -  Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)\n\n               -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human\n                  erythropoietin use is permitted)\n\n               -  Serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) or\n                  serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) > 3.0 x\n                  upper limit of normal (ULN)\n\n               -  Serum total bilirubin > 2.0 mg/dL\n\n          4. Prior history of malignancies, other than the disease being studied, unless the\n             subject has been free of the malignancy for ? 5 years from initiating study treatment,\n             with the following exceptions:\n\n               -  Basal cell carcinoma of the skin\n\n               -  Squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (T1a or T1b using the TNM\n                  [tumor, nodes, metastasis] clinical staging system).\n\n          5. Previous therapy with Pomalidomide\n\n          6. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone\n\n          7. Rash ? Grade 3 during prior thalidomide or lenalidomide therapy\n\n          8. Incidence of gastrointestinal disease that may significantly alter the absorption of\n             pomalidomide\n\n          9. Subjects with any one of the following:\n\n               -  Congestive heart failure (New York Heart Association Class III or IV)\n\n               -  Myocardial infarction within 12 months prior to starting study treatment\n\n               -  Unstable or poorly controlled angina pectoris, including Prinzmetal variant\n                  angina pectoris\n\n         10. Subjects who received any of the following within the last 14 days of initiation of\n             study treatment:\n\n               -  Plasmapheresis\n\n               -  Major surgery (kyphoplasty is not considered major surgery)\n\n               -  Radiation therapy (with the exception of radiation therapy to a pathological\n                  fracture site to enhance bone healing or to treat post-fracture pain that is\n                  refractory to narcotic analgesics)\n\n               -  Any anti-myeloma drug therapy\n\n         11. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer)\n             of initiating study treatment\n\n         12. Subjects with conditions requiring chronic steroid or immunosuppressive treatment,\n             such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need\n             additional steroid or immunosuppressive treatments in addition to the study treatment.\n             Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent)\n             within 3 weeks prior to initiating study treatment\n\n         13. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not\n             be eligible to participate in this study\n\n         14. Any condition, including the presence of laboratory abnormalities, which places the\n             subject at unacceptable risk if he/she were to participate in the study\n\n         15. Any serious medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the subjects from signing the informed consent form\n\n         16. Pregnant or breastfeeding females

Progression following prior ofatumumab-based therapy

Duodenal polyposis as a stratification site; one or more of the following:

No response, progression, or relapse (according to 2006 International Working Group [IWG] criteria) following at least 4 cycles of either azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine or decitabine, or SGI-110 defined as drug-related >= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years

Prior disease progression/recurrence during or immediately following treatment with bevacizumab; any questions should be directed to the PI

Patient must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1\r\n* Tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

PRIMARY SITE (ONE OF THE FOLLOWING CRITERIA):

Subject has positive test result at the screening visit for one or more of the following:

Subject has hematopoietic failure at baseline as defined by one of the following:

Patients with relapsed multiple myeloma following autologous stem cell transplantation must have achieved at least partial response following additional chemotherapy (cohort 1):\r\n* Patients are eligible if relapse occurs with complex/high-risk cytogenetics or occurs with normal cytogenetics but within 15 months following the autologous transplant

Patients achieving < partial response following preceding chemotherapy (cohort 1) or < very good partial response following autologous stem cell transplantation (cohort 2)

Patients should agree to not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or tremelimumab

Resistant to or intolerant of hydroxyurea, that is, fulfilling at least 1 of the following criteria:

Patient must be available for follow-up; after 2 years of follow-up following post-treatment biopsy, telephone-based follow-up will be acceptable

Patients must have at least one \target lesion\ to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as \non-target\ lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

The patient must currently have at least one of the following:\r\n* Uncontrolled symptoms, defined as any of the following:\r\n** Headaches associated with mass effect\r\n** Uncontrolled seizures despite 2 different antiepileptic drug regimens (i.e., 2 antiepileptic drugs tested either sequentially or in combination)\r\n** Focal neurological symptoms\r\n** Cognitive symptoms or deficits OR\r\n* Tumor progression by serial magnetic resonance imaging (MRIs), defined as any of the following:\r\n** New or progressive enhancement\r\n** New or progressive T2 or fluid attenuated inversion recovery (FLAIR) signal abnormality OR\r\n* Age >= 40 years\r\n** NOTE: Patients aged less than 40 whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs, and who have no evidence of radiographic progression, are ineligible

Patients with the following hematologic malignancies will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) and the principal investigators:

Must have been treated with one of the following in first and/or second line:

CRITERIA FOR RANDOMIZATION\r\n* Participants must meet the following criteria to qualify for HD-ADE versus Clo/AraC randomization; participants who do not meet these criteria may still be enrolled, but will be treated on HD-ADE arm and will NOT be randomized

LOW RISK MEDULLOBLASTOMA (patients must meet all of the following criteria):

Progression following at least 6 weeks of standard doses of Herceptin (Arm A only)

Any of the following treatments, within the specified time frame, prior to the first dose of TAS4464:

ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:

Agree to abstain from donating blood while taking CC-122 or sorafenib and following discontinuation of their use.

Currently pregnant or nursing, or planning pregnancy (in the period up to 6 months) following the index procedure(s),

Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject received at least 3 prior anti-myeloma regimens including a proteasome\n             inhibitor (PI) and an immunomodulatory agent or is double-refractory to a PI and an\n             immunomodulatory agent.\n\n               -  Induction, bone marrow transplant with or without maintenance therapy is\n                  considered one regimen.\n\n               -  Refractory is defined as disease that is nonresponsive on therapy, or progresses\n                  within 60 days of last therapy. Nonresponsive disease is defined as either\n                  failure to achieve minimal response or development of progressive disease while\n                  on therapy.\n\n               -  For subjects who received more than 1 regimen containing a PI their disease must\n                  be refractory to the most recent PI containing regimen.\n\n               -  For subjects who received more than 1 regimen containing a immunomodulatory agent\n                  their disease must be refractory to the most recent immunomodulatory agent\n                  containing regimen.\n\n          2. All subjects must have failed Daratumumab (DARA) either as a single agent or in\n             combination on last Multiple myeloma (MM) therapy. Failure is defined as disease\n             progression(PD) on DARA either as a single agent or in combination.\n\n          3. Subject has measurable disease defined as:\n\n               1. M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis\n                  (uPEP): sPEP ? 0.5 g/dL or uPEP ? 200 mg/24 hours) and/or\n\n               2. Light chain MM without measurable disease in the serum or the urine: serum\n                  immunoglobulin free light chain ?10 mg/dL and abnormal serum immunoglobulin kappa\n                  lambda free light chain ratio\n\n          4. Subject achieved a response (minimal response [MR] or better) to at least 1 prior\n             treatment regimen.\n\n          5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2\n             or less.\n\n          6. Subject's toxicities resulting from previous therapy (including peripheral neuropathy)\n             have resolved or stabilized to ? Grade 1.\n\n          7. Subject is at least 18 years of age the time of signing the informed consent form\n             (ICF).\n\n          8. Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          9. Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n         10. Females of childbearing potential (FCBP) must:\n\n             a. Have 2 negative pregnancy tests as verified by the investigator prior to starting\n             study treatment. This applies even if the subject practices true abstinence from\n             heterosexual contact.\n\n             i. Negative serum pregnancy test at screening ii. Negative serum or urine pregnancy\n             test (investigator's discretion) within 72 hours prior to starting study treatment\n             (Cycle 1, Day 1), and before beginning each subsequent cycle of treatment, and after\n             end of study treatment.\n\n             b. Either practice true abstinence from heterosexual contact (which must be reviewed\n             on a monthly basis and source documented) or agree to use, and be able to comply with,\n             effective contraception without interruption (eg, oral, inject able, or implantable\n             hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive\n             with spermicide; true abstinence; or vasectomized partner), 28 days prior to starting\n             study treatment, during the study therapy (including dose interruptions), and for at\n             least 90 days after discontinuation of study treatment.\n\n             c. Agree to abstain from breastfeeding during study participation and for at least 90\n             days after the last dose of Daratumumab (DARA) or Durvalumab (DURVA), whichever is\n             later.\n\n             d. Refrain from egg cell donation for at least 90 days after the final dose of DURVA\n             or DARA, whichever is later.\n\n         11. Male subjects must:\n\n               1. Either practice true abstinence (which must be reviewed on a monthly basis) or\n                  agree to use a condom during sexual contact with a pregnant female or a female of\n                  childbearing potential while participating in the study, during dose\n                  interruptions and for at least 90 days following study treatment discontinuation,\n                  even if he has undergone a successful vasectomy.\n\n               2. Refrain from sperm donation for at least 90 days after the final dose of DURVA or\n                  DARA, whichever is later.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Subject has had prior exposure to anti-CTLA-4, anti-PD-1 (Programmed cell death-1),\n             anti-PD-L1 (Programmed death-ligand 1) Monoclonal antibody (mAbs), or cancer vaccines\n\n          2. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks\n             before the date of randomization.\n\n          3. History of organ or allogeneic stem cell transplantation\n\n          4. Subject received any of the following within the last 14 days of initiating study\n             treatment:\n\n               1. Plasmapheresis\n\n               2. Major surgery (as defined by the investigator)\n\n               3. Radiation therapy other than local therapy for myeloma associated bone lesions\n\n               4. Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in\n                  combination with other agents given with it)\n\n          5. Subject received prior treatment with a monoclonal antibody within 5 half-lives of\n             initiating study treatment, other than DARA.\n\n          6. Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for\n             cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions\n             (eg, insulin for diabetes and hormone replacement therapy) is acceptable.\n\n          7. Subject has any of the following laboratory abnormalities:\n\n               1. Absolute neutrophil count (ANC) < 1,000/µL\n\n               2. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to\n                  reach this level)\n\n               3. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject\n                  to reach this level)\n\n               4. Creatinine clearance (CrCl) < 45 mL/min (calculated using the Cockcroft-Gault\n                  formula or directly calculated from the 24-hour urine collection method)\n\n               5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)\n\n               6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×\n                  upper limit of normal (ULN)\n\n               7. Serum total bilirubin > 1.5 × upper limit of normal (ULN) or > 3.0 mg/dL for\n                  subjects with documented Gilbert's syndrome\n\n          8. Subject has clinical evidence of central nervous system (CNS) or pulmonary\n             leukostasis, disseminated intravascular coagulation, or CNS MM\n\n          9. Subject has known chronic obstructive pulmonary disease (COPD) with a forced\n             expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that forced\n             expiratory testing (FEV1) is required for subjects suspected of having COPD and\n             subjects must be excluded if FEV1 is < 50% of predicted normal.\n\n         10. Subject has known moderate or severe persistent asthma within the past 2 years or\n             uncontrolled asthma of any classification. Note that subjects who currently have\n             controlled intermittent asthma or controlled mild persistent asthma are allowed to\n             participate in the study.\n\n         11. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome\n             (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),\n             or amyloidosis\n\n         12. Subject has nonsecretory MM\n\n         13. Subject has known allergy or hypersensitivity to study drug formulations\n\n         14. Subject has active or prior documented autoimmune or inflammatory disorders (including\n             inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis, celiac\n             disease, irritable bowel disease, or other serious gastrointestinal chronic conditions\n             associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia\n             gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the\n             past 3 years prior to the start of treatment. The following are exceptions to this\n             criterion:\n\n               1. Subjects with vitiligo or alopecia.\n\n               2. Subjects with hypothyroidism (eg, following Hashimoto's disease) stable on\n                  hormone replacement.\n\n               3. Psoriasis not requiring systemic treatment.\n\n         15. Subject has history of primary immunodeficiency\n\n         16. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active\n             hepatitis B or active hepatitis A or C.\n\n         17. Subject has received live, attenuated vaccine within 30 days prior to the first dose\n             of DURVA (NOTE: Subjects, if enrolled, should not receive live vaccine during the\n             study and through 30 days after the last dose of DURVA)\n\n         18. Subject is currently using or has used immunosuppressive medication within 14 days\n             prior to the first study dose of study treatment. The following are exceptions to this\n             criterion:\n\n               1. Intranasal, topical, inhaled, or local steroid injections (eg, intra-articular\n                  injection).\n\n               2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of\n                  prednisone or equivalent.\n\n               3. Steroids as premedication for hypersensitivity reactions (eg, infusion-related\n                  reactions, computed tomography [CT] scan premedication).\n\n         19. Subject has any one of the following:\n\n               1. Clinically significant abnormal Electrocardiogram (ECG) finding at screening\n\n               2. Congestive heart failure (New York Heart Association Class III or IV)\n\n               3. Myocardial infarction within 12 months prior to starting study treatment\n\n               4. Unstable or poorly controlled angina pectoris, including Prinzmetal variant\n                  angina pectoris\n\n         20. Subject has prior history of malignancies, other than MM, unless the subject has been\n             free of the disease for ? 5 years with the exception of the following noninvasive\n             malignancies:\n\n               1. Basal cell carcinoma of the skin\n\n               2. Squamous cell carcinoma of the skin\n\n               3. Carcinoma in situ of the cervix\n\n               4. Carcinoma in situ of the breast\n\n               5. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM\n                  [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is\n                  curative\n\n         21. Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to\n             become pregnant during the participation in the study.\n\n         22. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study\n\n         23. Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study\n\n         24. Subject has any condition that confounds the ability to interpret data from the study

Key Inclusion Criteria:\n\n          -  Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition\n             (Rajkumar et al 2014):\n\n          -  Clonal bone marrow plasma cells ? 10% or biopsy-proven bony or extramedullary\n             plasmacytoma and any one or more of the following myeloma defining events:\n\n          -  Evidence of end organ damage that can be attributed to the underlying plasma cell\n             proliferative disorder\n\n          -  Any one or more of the following biomarkers of malignancy:\n\n               1. Clonal bone marrow plasma cell percentage ? 60%\n\n               2. Involved: uninvolved serum free light chain ratio ? 100\n\n               3. >1 focal lesions on MRI studies\n\n          -  Patient with measurable disease defined by at least 1 of the following conditions\n             present at screening:\n\n          -  Serum M-protein by Protein Electrophoresis (PEP) ? 1.0 g/dL (? 10 g/L).\n\n          -  Urine M-protein by PEP ? 200 mg/24 hours. Involved serum free light chain level ? 10\n             mg/dL (? 100 mg/L), provided that the serum free light chain ratio is abnormal.\n\n          -  Patient eligible for autologous stem cell transplantation based on the investigator's\n             clinical judgment.\n\n          -  Patient with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 2\n\n          -  Patient's age ? 18 and <75 years at time of signing the informed consent\n\n          -  Patient provided written informed consent prior to any screening procedures\n\n          -  Women of childbearing potential (WOCBP) with a negative serum pregnancy test at\n             screening and a negative urine pregnancy test at baseline\n\n        Key Exclusion Criteria:\n\n        Patients eligible for this study must not meet any of the following criteria:\n\n          -  Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone;\n             bisphosphonates are permitted only if commenced prior to the start of screening\n             period)\n\n          -  Unresolved diarrhea ? CTCAE grade 2 or presence of medical condition associated with\n             chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).\n\n          -  Allogeneic stem cell transplant recipient presenting with graft versus host disease\n             either active or requiring immunosuppression\n\n          -  Patient shown intolerance to bortezomib or to dexamethasone or components of these\n             drugs or has any contraindication to one or the other drug, following locally\n             applicable prescribing information\n\n          -  Patient with rade ? 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain\n             on clinical examination at screening\n\n          -  Patient received prior treatment with DAC inhibitors including Panobinostat\n\n          -  Patient needing valproic acid for any medical condition during the study or within 5\n             days prior to first administration of panobinostat/study treatment.\n\n          -  Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted\n             only if commenced prior to the start of screening period)\n\n          -  Patient who received:\n\n               1. prior anti-myeloma chemotherapy or medication including Immunomodulator (IMiDs)\n                  and Dex ? 3 weeks prior to start of study.\n\n               2. experimental therapy or biologic immunotherapy including monoclonal antibodies ?\n                  4 weeks prior to start of study.\n\n               3. prior radiation therapy ? 4 weeks or limited field radiotherapy ? 2 weeks prior\n                  start of study.\n\n          -  Patient has not recovered from all therapy-related toxicities associated with above\n             listed treatments to < grade 2 CTCAE.\n\n          -  Patient undergone major surgery ? 2 weeks prior to starting study drug or who have not\n             recovered from side effects of such therapy to < grade 2 CTCAE\n\n          -  Patients with evidence of mucosal or internal bleeding\n\n          -  Clinically significant, uncontrolled heart disease and/or recent cardiac event (within\n             6 month prior to screening)\n\n          -  Inability to determine the Fridericia's Correction Formula (QTc) F interval\n\n          -  Patient with an impairment of gastrointestinal (GI) function or GI disease that may\n             significantly alter the absorption of panobinostat (e.g. ulcerative disease,\n             uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or\n             small bowel resection)\n\n          -  Sexually active males unless they use a condom during intercourse while taking the\n             drug during treatment, and for 6 months after stopping treatment\n\n          -  Pregnant or nursing (lactating) women.

Having documented disease progression on enzalutamide defined by 1 or more of the following criteria:

One of the following is required:

The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

One of the following is required:

Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or peritoneal). Must have disease that has relapsed following at least one prior line of chemotherapy.

Candidate committed to HCT independent of participation in this study, with the following requirements:

Treatment with chronic immunosuppressant (e.g., cyclosporine following transplantation)

Subject has adequate biological parameters as demonstrated by the following blood counts at screening (obtained ? 14 days prior to starting Cycle 1 Day 1):

Subject has the following blood chemistry levels at screening (obtained ? 14 days prior to starting Cycle 1 Day 1):

Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).

Presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

Disease progression following radiation & TMZ

Subject requires the use of the following concomitant treatments/procedures at any time, per protocol.

Have had anti-cancer treatment following liver resection that exceeded a duration of 6 months.

Unresolved immune related adverse events following prior biological therapy.

interval of at least 3 months following initial radiotherapy and temozolomide

Patients must not have the following foods/ supplements at least 7 days prior to initiation of and during study treatment:

Patients with other cardiac diseases may be excluded at the discretion of the principal investigator (PI) following consultation with cardiology consultants

High-risk NMIBC defined by the following: BCG-unresponsive NMIBC: Persistence of high-grade CIS at 6 months following an adequate course of BCG; or Stage/grade progression at 3 months after induction BCG; or Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs less than (<) 6 months after the last exposure to BCG BCG-relapsing NMIBC: Recurrence of high-grade CIS after achieving a disease-free state following induction of an adequate course of BCG that occurs greater than or equal to (>/=) 6 months after the last exposure to BCG Very high-risk (VHR) BCG-naïve NMIBC: VHR NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than [>] 3 centimeters [cm]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma

Inclusion Criteria:\n\n        All subjects must meet the following criteria for inclusion:\n\n          -  ? 18 years of age\n\n          -  Life expectancy of ? 3 months\n\n          -  Histological or cytological evidence of advanced and/or metastatic carcinoma or\n             melanoma , excluding sarcoma\n\n          -  At least 1 measurable disease lesion as defined by RECIST 1.1\n\n          -  Serum creatinine clearance ? 60 mL/min and serum creatinine ? 2.0 x the upper limit of\n             normal (ULN) as determined by either of the following: Estimation as calculated by\n             Cockcroft-Gault equation or Direct measurement by 24-hour urine collection\n\n          -  Total bilirubin ? 1.5 x ULN (unless elevated due to Gilbert's syndrome)\n\n          -  Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ? 2.5 x\n             ULN (<5x ULN if liver metastasis)\n\n          -  Adequate hematological function, defined as absolute neutrophil count ?1.5 x 109/L,\n             hemoglobin ? 9.0 g/dL, and platelet count ? 100 x 109/L\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status ? 2 (corresponds to\n             Karnofsky Performance Status (KPS) ? 60%)\n\n        Subjects entering Part A, B, C, or D must also meet the following additional criterion:\n\n        • Failure to respond to standard therapy, or for whom no appropriate therapies are\n        available (based on the judgement of the Investigator)\n\n        Subjects entering Part D, E, F or G must also meet the following additional criterion:\n\n        • Willing to undergo 1 pre-treatment and 1 on-treatment tumor biopsy\n\n        Subjects entering Part E must also meet the following additional criteria:\n\n          -  Histological or cytological evidence of NSCLC, melanoma, , human papillomavirus (HPV)\n             positive or HPV negative SCCHN (oral cavity, pharynx, hypopharynx, larynx,\n             nasopharyngeal [including undifferentiated nasopharyngeal carcinoma]), or another\n             tumor type to be determined\n\n          -  Failure to respond to standard therapy, or for whom no appropriate therapies are\n             available (based on the judgment of the Investigator The most recent treatment prior\n             to study entry must be an anti-PD-1 or anti-PD-L1 antibody given as either monotherapy\n             or in combination\n\n          -  Subjects with NSCLC Tumors that harbor an actionable genetic alteration for which\n             there is a corresponding approved therapy for that specific alteration (including but\n             not limited to alterations in EGFR, ALK, and ROS) must have progressed on, or had\n             intolerance to, the respective therapy\n\n        Subjects entering Part F must also meet the following additional criteria:\n\n          -  Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone\n             receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-)\n             Breast Cancer by local laboratory testing, based on last available tumor tissue; or\n             another tumor type to be determined\n\n               -  ER/PgR negativity to follow local guidelines\n\n               -  If IHC HER2 2+, a negative FISH test is required\n\n               -  Inflammatory triple negative breast cancer is allowed\n\n          -  Must have received and failed/progressed a cytotoxic chemotherapy as first line\n             therapy per standard of care\n\n          -  No prior anti-PD-1 or anti-PD-L1 therapy\n\n        Subjects entering Part G must also meet the following additional criteria:\n\n          -  Histological or cytological evidence of ACC, mesothelioma, or another tumor type to be\n             determined\n\n               -  Both pleural and peritoneal mesothelioma are allowed\n\n               -  Epithelioid, sarcomatoid, or biphasic mesothelioma subtypes are allowed\n\n          -  Progression after at least first line available therapy\n\n        Exclusion Criteria:\n\n        Subjects are to be excluded from the study if they meet any of the following criteria:\n\n          -  Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine\n             protein, or known hypersensitivity to any excipient in the study drugs\n\n          -  Major surgery within 4 weeks prior to Screening\n\n          -  Subjects who have been treated with chemotherapy, biologic therapy, or other\n             investigational agent within < 5 times the half-life of the agent or < 28 days\n             (whichever is shorter) of starting study drug\n\n        NOTE: Subjects whose immediate prior treatment was with nivolumab may start study drug 2\n        weeks after the last dose of nivolumab\n\n          -  Symptomatic or untreated brain metastases\n\n          -  Primary central nervous system (CNS) malignancy\n\n          -  Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus\n\n          -  Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic\n             steroids\n\n          -  Ongoing systemic bacterial, fungal, or viral infections at Screening\n\n        NOTE: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically\n        excluded if all other inclusion/exclusion criteria are met\n\n          -  Administration of a live vaccine within 6 weeks of first dose of study drug\n\n          -  Administration of any of the following within 1 week prior to the administration of\n             study drug:\n\n               -  Strong inhibitors or inducers of CYP3A4, including grapefruit products and herbal\n                  supplements\n\n               -  P-glycoprotein (P-gp) inhibitors\n\n               -  Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow\n                  therapeutic range\n\n               -  Medications associated with QTc interval prolongation or Torsades de Pointes\n\n          -  Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of\n             triplicate readings) NOTE: criterion does not apply to subjects with a right or left\n             bundle branch block\n\n          -  Parts C, D-Annex, and E only: Subjects with active, known, or suspected autoimmune\n             disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due\n             to autoimmune condition only requiring hormone replacement, psoriasis not requiring\n             systemic treatment, or conditions not expected to recur in the absence of an external\n             trigger are permitted to enroll\n\n          -  Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg,\n             gastric bypass surgery, gastrectomy)\n\n          -  Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of\n             the cervix, or prostate intraepithelial neoplasia\n\n          -  Past medical history of interstitial lung disease, drug-induced interstitial lung\n             disease, radiation pneumonitis which required steroid treatment, or any evidence of\n             clinically active interstitial lung disease\n\n          -  History of peptic ulcer and/or gastrointestinal bleed\n\n          -  History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia\n             requiring medication or mechanical control within the last 6 months prior to Screening\n\n          -  Unstable or severe uncontrolled medical condition (eg, unstable cardiac function,\n             unstable pulmonary condition including pneumonitis and/or interstitial lung disease,\n             uncontrolled diabetes) or any important medical illness or abnormal laboratory finding\n             that would, in the Investigator's judgment, increase the risk to the subject\n             associated with his or her participation in the study.

Satisfy at least one of the following criteria

mTNBC (confirmed from most recent tissue sample) meeting the following criteria:

Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to ? 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows: a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions: i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria;

Subjects must have the following lab values:

Agree to abstain from donating blood while taking IP and following discontinuation of IP.

Subjects in Cohort 2 of Arm C must meet the following criteria:

History of second malignancies with life expectancy of < 2 years or requirement of therapy that would confound study results. This does not include the following:

Chemotherapy-refractory disease, defined as one of more of the following:

Any of the following as this regimen may be harmful to a developing fetus or nursing child:

Bone metastases and one of the following:

MDS refractory to treatment with HMA therapy or with recurrence or progression of MDS following a response to an HMA

Patients must have relapsed or refractory disease following:

Have either of the following diagnoses:

Documented clinical benefit following 6th cycle of DI-Leu16-IL2.

Bone metastases and one of the following:

Patient must have an advanced stage malignancy defined as meeting at least one of the following criteria:

Patient has received any of the following treatments within the specified timeframe:

Patients must have one of the following:

History of exposure to the following cumulative doses of anthracyclines:

The two most recent measurements of serum testosterone prior to enrollment must fulfill the following criteria:

Prior therapy must meet all of the following criteria:

For leukapheresis, patients must meet the following criteria (any exceptions to this will require prior approval by the apheresis director and principal investigator [PI]):

The presence of any of the following will exclude a subject from enrollment:

Primary resistance or acquired resistance (i.e., acquired resistance will be defined as disease progression following a period of response defined as >= 50% decline in PSA within 12 weeks of starting therapy and not otherwise meeting criteria for primary resistance) to any of the following agents/combinations of therapy:

History of any of the following toxicities associated with a prior immunotherapy:

For patients who have undergone resection of recurrent or progressive tumor prior to study enrollment, the following conditions must apply:

Bone metastases and one of the following:

Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)

Have taken any of the following drugs within 7 days prior to Study Day 1:

Patients with Ph+ B-precursor ALL, with any of the following:

Patients enrolling on the retreatment cohort must have locally and systemically stable disease following the definite local treatment.

Bone metastases and one of the following:

Patients with any of the following serum chemistry abnormalities at baseline:

Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of\n        the following criteria are met:\n\n          1. Female subjects, age ? 18 years at the time informed consent is signed\n\n          2. Pathologically confirmed adenocarcinoma of the breast\n\n          3. Pathologically confirmed as triple negative, source documented, defined as both of the\n             following\n\n               1. Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: < 1% of tumor\n                  cell nuclei are immunoreactive in the presence of evidence that the sample can\n                  express ER or PgR (positive intrinsic controls)\n\n               2. Human Epidermal Growth Factor Receptor 2 (HER2) negative as per American Society\n                  of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines i.\n                  Immunohistochemistry (IHC) 0 or 1 Fluorescence In Situ Hybridization (FISH)\n                  negative (or equivalent negative test). Subjects with IHC 2 must have a negative\n                  by Fluorescence In Situ Hybridization (FISH),, (or equivalent negative test).\n\n          4. Subjects with prior breast cancer history of different phenotypes (ie, ER/PgR/HER2\n             positive) must have pathologic confirmation of triple negative disease in at least one\n             of the current sites of metastasis\n\n          5. Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy;\n             unless (a) anthracycline treatment was not indicated or was not the best treatment\n             option for the subject in the opinion of the treating physician; and (b) anthracycline\n             treatment remains not indicated or, in the opinion of the treating physician, is not\n             the best treatment option for the subject's metastatic disease.\n\n             a. Newly diagnosed subjects presenting with TNMBC are eligible for the study if\n             anthracycline treatment is not indicated or is not the best treatment option for the\n             subject in the opinion of the treating physician.\n\n          6. Subjects with measurable metastatic disease, defined by Response Evaluation Criteria\n             in Solid Tumors 1.1 (RECIST 1.1) guidelines\n\n          7. Life expectancy ? 16 weeks from randomization\n\n          8. No prior cytotoxic chemotherapy for metastatic breast cancer. Prior immunotherapy\n             and/or monoclonal antibody therapy are acceptable. Prior treatments must have been\n             discontinued at least 30 days prior to start of study treatment and all related\n             toxicities must have resolved to Grade 1 or less.\n\n          9. Prior neoadjuvant or adjuvant chemotherapy, if given, must have been completed at\n             least 6 months before randomization with all related toxicities resolved, and\n             documented evidence of disease progression per RECIST 1.1 guidelines is required.\n\n             a. If prior neoadjuvant or adjuvant chemotherapy contained taxane, gemcitabine, or\n             platinum agents, the treatment must have completed at least 12 months before\n             randomization\n\n         10. Prior radiotherapy must have completed before randomization, with full recovery from\n             acute radiation side effects. At least one measurable lesion must be completely\n             outside the radiation portal or there must be unequivocal radiologic or clinical exam\n             proof of progressive disease within the radiation portal, in accordance with RECIST\n             1.1 guidelines\n\n         11. At least 30 days from major surgery before randomization, with full recovery\n\n         12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n\n         13. Subject has the following blood counts at screening:\n\n               -  Absolute Neutrophil Count (ANC) ? 1500/mm^2 ;\n\n               -  Platelets ? 100,000/mm^2 ;\n\n               -  Hemoglobin (Hgb) ? 9 g/dL\n\n         14. Subject has the following blood chemistry levels at screening:\n\n               -  Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT),\n                  Alanine Aminotransferase (ALT ) Serum Glutamic Pyruvate Transaminase (SGPT) ? 2.5\n                  x upper limit of normal range (ULN); if hepatic metastases present ? 5.0 x ULN\n\n               -  Total serum bilirubin ? ULN; or total bilirubin ? 3.0 × ULN with direct bilirubin\n                  within normal range in subjects with documented Gilbert's Syndrome\n\n               -  Creatinine clearance > 60 mL/min (by Cockcroft-Gault)\n\n         15. Females of child-bearing potential [defined as a sexually mature women who (1) have\n             not undergone hysterectomy (the surgical removal of the uterus) or bilateral\n             oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally\n             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time\n             during the preceding 24 consecutive months)] must:\n\n               -  Demonstrate a negative serum pregnancy test result at screening (performed by\n                  central lab) confirmed by local negative urine pregnancy dipstick within 72 hours\n                  prior to the first dose of IP); pregnancy test with sensitivity of at least 25\n                  mIU/mL; and\n\n               -  Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis) or agree to use, and be able to comply with, two\n                  physician approved effective contraception methods (oral, injectable, or\n                  implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier\n                  contraceptive with spermicide; or vasectomized partner) without interruption for\n                  28 days or longer as required by local guidelines, prior to starting study drug,\n                  during the study therapy (including dose interruptions), and for 28 days after\n                  discontinuation of the study or longer as required by local guidelines\n\n         16. Females must abstain from breastfeeding starting at randomization, during study\n             participation and for 28 days or longer as required by local guidelines, after IP\n             discontinuation\n\n         17. Understand and voluntarily sign an informed consent document prior to any study\n             related assessments/procedures are conducted\n\n         18. Able to adhere to the study visit schedule and other protocol requirements\n\n        Exclusion Criteria:\n\n        A subject will not be eligible for inclusion in this study if any of the following criteria\n        apply:\n\n          1. Male subjects\n\n          2. Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior\n             immunotherapy & monoclonal antibody therapy are acceptable.\n\n          3. Subjects who received prior cytotoxic chemotherapy after incomplete resection of\n             locoregional recurrent disease\n\n          4. History of, or known current evidence of brain metastasis, including leptomeningeal\n             involvement.\n\n          5. Subjects with bone as the only site of metastatic disease\n\n          6. Subjects with regional lymph node as the only site of metastatic disease\n\n          7. Serious intercurrent medical or psychiatric illness, including serious active\n             infection\n\n          8. History of class II-IV congestive heart failure or myocardial infarction within 6\n             months of randomization\n\n          9. History of other primary malignancy in the last 5 years prior to randomization.\n             Subjects with prior breast cancer history are eligible, however, the most recently\n             obtained biopsy must demonstrate triple negative disease (source documented). Subjects\n             with prior history of in situ cancer or basal or localized squamous cell skin cancer\n             are eligible.\n\n         10. Subjects with a history of interstitial lung disease, history of slowly progressive\n             dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis,\n             pulmonary hypersensitivity pneumonitis or multiple uncontrolled or unstable allergies\n             which, in the opinion of the investigator, may lead to serious complications\n\n         11. Peripheral neuropathy Grade ? 2 by National Cancer Institute Common Terminology\n             Criteria for Adverse Events (NCI CTCAE) v4.0\n\n         12. Subjects who have received an investigational product within the previous 4 weeks\n             prior to randomization\n\n         13. Subject is currently enrolled, or will enroll in a different clinical study in which\n             investigational therapeutic procedures are performed or investigational therapies are\n             administered while participating in this study\n\n         14. Pregnant or nursing women\n\n         15. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or\n             any other platin, or nucleoside analogue agents\n\n         16. Any significant medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the subject from participating in the study\n\n         17. Any condition including the presence of laboratory abnormalities, which places the\n             subject at unacceptable risk if she were to participate in the study\n\n         18. Any condition that confounds the ability to interpret data from the study\n\n         19. History of seropositive human immunodeficiency virus (HIV)\n\n         20. Subjects who are receiving immunosuppressive or myelosuppressive medications that\n             would, in the opinion of the investigator, increase the risk of serious neutropenic\n             complications

Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:

Anticancer treatment within 4 weeks of randomization, with the following exceptions:

Objective, measureable, symptomatic organ involvement, defined as one or more of the following:

Specifically, subjects must meet one or more of the following criteria:

Patients with any of the following serum chemistry abnormalities at baseline:

Patients must meet one or more of the following indications for treatment:

Inclusion Criteria:\n\n        Patients are eligible if they:\n\n          1. have undergone noncardiac surgery;\n\n          2. are ?45 years of age;\n\n          3. have suffered MINS based upon fulfilling one of the following criteria: A. Elevated\n             troponin or CK-MB measurement with one or more of the following defining features i.\n             ischemic signs or symptoms (i.e., chest, arm, neck, or jaw discomfort; shortness of\n             breath, pulmonary edema); ii. development of pathologic Q waves present in any two\n             contiguous leads that are ?30 milliseconds; iii. electrocardiogram (ECG) changes\n             indicative of ischemia (i.e., ST segment elevation [?2 mm in leads V1, V2, or V3 OR ?1\n             mm in the other leads], ST segment depression [?1 mm], OR symmetric inversion of T\n             waves ?1 mm) in at least two contiguous leads; iv. new LBBB; or v. new or presumed new\n             cardiac wall motion abnormality on echocardiography or new or presumed new fixed\n             defect on radionuclide imaging B. Elevated troponin measurement after surgery with no\n             alternative explanation (e.g., pulmonary embolism, sepsis) to myocardial injury; AND\n\n          4. provide written informed consent to participate within 35 days of suffering their\n             MINS.\n\n        Exclusion Criteria:\n\n        Patients meeting any of the following criteria will be excluded:\n\n          1. hypersensitivity or known allergy to dabigatran;\n\n          2. history of intracranial, intraocular, or spinal bleeding;\n\n          3. hemorrhagic disorder or bleeding diathesis;\n\n          4. known hepatic impairment or liver disease expected to have an impact on survival;\n\n          5. condition that requires therapeutic dose anticoagulation (e.g., prosthetic heart\n             valve, venous thromboembolism, atrial fibrillation);\n\n          6. currently using or plan to initiate rifampicin, cyclosporine, itraconazole,\n             tacrolimus, ketoconazole, or dronedarone;\n\n          7. women who are pregnant, breastfeeding, or of childbearing potential who refuse to use\n             a medically acceptable form of contraception throughout the study;\n\n          8. investigator considers the patient unreliable regarding requirement for study\n             follow-up or study drug compliance; OR\n\n          9. previously enrolled in the MANAGE Trial.\n\n        Also excluded will be patients in whom any of the following criteria persist beyond 35 days\n        of their suffering MINS:\n\n          1. the attending surgeon believes it is not safe to initiate therapeutic dose\n             anticoagulation therapy;\n\n          2. the attending physician believes ASA, intermittent pneumatic compression, or elastic\n             stockings are not sufficient for venous thromboembolism (VTE) prophylaxis and that the\n             patient requires a prophylactic-dose anticoagulant;\n\n          3. the patient has an indwelling epidural or spinal catheter that cannot be removed, or\n             the first dose of dabigatran will occur within 4 hours of epidural catheter removal;\n             OR\n\n          4. estimated glomerular filtration rate (eGFR) <35 ml/min as estimated by calculated\n             creatinine clearance.\n\n          5. it is expected that the patient will undergo cardiac catheterization for MINS.\n\n        Exclusion Criteria Specific to Patients in the Omeprazole Factorial Component of the Trial:\n\n        Patients meeting any of the following criteria:\n\n          1. hypersensitivity or known allergy to omeprazole;\n\n          2. requirement for a proton pump inhibitor, an H2-receptor antagonist, sucralfate,\n             atazanavir, clopidogrel, or misoprostol;\n\n          3. esophageal or gastric variceal disease; OR\n\n          4. patient declines participation in the omeprazole arm of MANAGE.

Progressive disease defined as one or more of the following three criteria (Note: subjects who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen):

Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):

Current or planned glucocorticoid therapy, with the following exceptions:

Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)

Inclusion Criteria:\n\n        Among other criteria, patients must meet the following conditions to be eligible for the\n        study:\n\n          1. 18 years of age or older.\n\n          2. Body Weight ? 120 kg.\n\n          3. Histologic diagnosis of either a B-cell or T-cell hematologic malignancy known to\n             express CD27 or one of the following solid tumors: metastatic melanoma, renal (clear)\n             cell carcinoma, hormone-refractory prostate adenocarcinoma, ovarian cancer, colorectal\n             adenocarcinoma or non-small cell lung cancer. For the solid tumor expansion cohorts,\n             enrollment is limited to the following solid tumors: melanoma and renal cell\n             carcinoma.\n\n          4. Tumor must be recurrent or treatment refractory with no remaining alternative,\n             approved therapy options, with the following exception: melanoma patients enrolled in\n             the expansion phase must have previously received ipilimumab and, for patients with\n             the BRAF V600E mutation, vemurafenib, or have been offered such therapies and refused,\n             and patients must have progressive disease subsequent to previous therapies.\n\n          5. Measurable or evaluable disease.\n\n          6. Have adequate blood, bone marrow, liver and kidney function as determined by\n             laboratory tests.\n\n          7. If of childbearing potential (male or female), agree to practice an effective form of\n             contraception during study treatment.\n\n          8. Have little or no side effects remaining from prior cancer therapies.\n\n          9. Provide written informed consent.\n\n        Exclusion Criteria:\n\n        Among other criteria, patients who meet the following conditions are NOT eligible for the\n        study:\n\n          1. Known prior primary or metastatic brain or meningeal tumors.\n\n          2. Receiving treatment with immunosuppressive agents, including any systemic steroids.\n\n          3. Active infection requiring systemic therapy, known HIV infection, or positive test for\n             hepatitis B surface antigen or hepatitis C.\n\n          4. Is being treated for anti-coagulation (i.e. warfarin) for reasons other than catheter\n             patency.\n\n          5. Women who are pregnant or lactating.\n\n          6. Prior allogeneic bone marrow transplant.\n\n          7. Autologous bone marrow transplant within 100 days of first dosing.\n\n          8. Recent chemotherapy or other anti-cancer therapy (within 2 - 14 weeks depending on\n             treatment type).\n\n          9. Systemic radiation therapy within 4 weeks or prior focal radiotherapy within 2 weeks\n             prior to first dosing.

Recipient must have one of the following diagnoses:

Recipient must not have had (the following therapies within the following timeframe):

Patients eligible for HSCT at the time of screening. However, patients who meet one or both of the following criteria may be eligible for study participation:

Patients with relapsed disease following a prior HSCT may be enrolled into this study as an alternative to a second HSCT or as a bridge-to-transplant regimen.

Relapsed is defined as experiencing PD that requires therapy but which is not refractory following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.

Patients with HER2-positive disease must have progressed on or following trastuzumab

Vital signs criteria defined as 3 or more of the following at Baseline:

b. ?1 prior therapy and one of the following abnormalities: 17p del, p53, 1q amp, 1p del, t(4;14)

One or more of the following indications for treatment:

Because the effects of ofatumumab on fetuses and nursing infants are not known, the following are ineligible for study entry:

presence of at least one of the following B-symptoms:

Patient had recurrence of osteosarcoma in the lung following standard therapy including: adriamycin, cisplatin, ifosfamide and methotrexate.

Neuroblastoma\r\n * Neuroblastoma patients will be eligible if relapse occurs following an autologous transplant or if the patient relapses following initial treatment, but is not eligible for an autologous transplant\r\n * Patients who do not achieve a CR with initial therapy will also be eligible provided they can be rendered free of bulky disease as defined above

Two out of three of the following (in peripheral blood): neutrophils less than 0.5 x 10^9/L; platelets less than 20 x 10^9/L; reticulocytes less than 20 x 10^9/L

All patients must have completed therapy including intensive induction followed by ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor; examples of such therapies include:              \r\n* Following treatment per A3973 protocol\r\n* Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol\r\n* Following treatment per CCG3891\r\n* Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02\r\n* Enrollment on or following treatment per ANBL02P1\r\n* Enrollment on or following treatment per ANBL07P1\r\n* Tandem transplant patients are eligible:                     \r\n** Following treatment on or per ANBL0532\r\n** Following treatment per POG 9640\r\n** Following treatment per COG ANBL00P1\r\n** Following treatment per CHP 594/Dana-Farber Cancer Institute (DFCI) 34-DAT

Subject who requires the following medications will be excluded:

Patients with other cardiac diseases may be excluded at the discretion of the principal investigator (PI) following consultation with cardiology consultants

Patients previously treated with carfilzomib are eligible as long as they meet the following criteria:

Previous treatment with all of the following: lapatinib, and trastuzumab emtansine; (patients are eligible if treated with 3 or less of these agents)

Patients must be at increased risk for cardiotoxicity defined by at least one of the following:\r\n* Previous anthracycline exposure, OR\r\n* 1 or more of the following risk factors for heart disease:\r\n** Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography (ECHO) read\r\n** Age >= 65\r\n** Body mass index (BMI) >= 30 kg/m^2\r\n** Current or prior anti-hypertensive therapy\r\n** Diagnosis of coronary artery disease (CAD)\r\n** Diabetes mellitus\r\n** Atrial fibrillation/flutter

The use of memantine during or following radiation is NOT allowed

Thrombocytopenia with untransfused platelet counts < 20 x 10^9/L in the out-patient or in the in-patient setting and one of the following criteria:

Women must agree not to breast feed while on abemaciclib treatment and for at least three months following the last dose of study therapy

Subject has received or plans to receive the following therapy/treatment within the following periods prior to leukapheresis or lymphodepleting chemotherapy:

Subject requires treatment with or plans to use either of the following:

For participants in all combination arms (Cohorts A-E), use or consumption of any of the following substances:

Additionally, for participants in the ibrutinib combination arm (Cohort E), use or consumption of any of the following substances:

28 days from administration of prior cytotoxic therapy with the following exceptions:

Patient cannot be on the following medications: GABA analogues (such as Neurontin, Lyrica), tricyclic antidepressants (such as amitriptyline or nortriptyline)

Recurrent cancer following prior resection

The following exclusion criteria will avoid the possibility of preexisting muscle impairment: history of congenital myopathies; neurologic disorder involving sequelae of spinal derangement; disk disease; tremor and rigidity

Is a candidate for immediate hysterectomy, following evaluation by a physician

Planned surgeries or radiation treatment within 10 weeks following study inclusion

Receiving a G-CSF for one of the following indications:\r\n* Prevention/treatment of neutropenia along with treatment for leukemia or lymphoma\r\n* Mobilization of hematopoietic progenitor cells\r\n* Neutropenia prevention following autologous hematopoietic cell transplant

Has all of the following:

Hearing levels that interfere with following test instruction

For Aim 2, all patients must meet the following criteria:

Patients are to be excluded from randomization for Aim 2 of this study if they meet any of the following criteria:

Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID) Exclusions specific to Arms A and F (HCC) (Patients who meet any of the following specific exclusion criteria will be excluded from enrollment in Arms A and F:)

Presence of islet cell neoplasms Exclusions Specific to Arm E (Metastatic Esophageal Cancer) (Patients who meet any of the following specific exclusion criteria will be excluded from enrollment in Arm E:)

Dose Escalation only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone

Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone

Prior treatment for AML, except for the following allowances:

Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFR?.

Participants must have organ and marrow function within the following parameters within 16 weeks before Segment B enrollment:

Evidence of any of the following conditions per subject self-report or medical chart review:

Subjects are to receive autologous PBSC transplant following mobilization, CD34+ cells collected by apheresis, and conditioning chemotherapy

Subjects for whom prophylactic platelet transfusions, at platelet counts >10× 109/L, are anticipated following PBSC transplant

Informal Caregivers will be accrued using the following inclusion criteria:\r\n* The primary informal caregiver as identified by patients participating in the study; this refers to either a family member or friend who will be providing the majority of care following surgery\r\n* Able to read and understand English

Note: Post-surgical patients should proceed to registration immediately following preregistration

Participants must meet any one of the following 6 criteria:

Participants with thyroid carcinoma or thyroid disease for whom systemic radioactive iodine therapy is part of planned diagnostic work-up or treatment within 2 months following the contrast mammogram study.

Participants with thyroid carcinoma or thyroid disease for whom systemic radioactive iodine therapy is part of planned diagnostic work-up or treatment within 2 months following the contrast mammogram study

Women scheduled for screening WBUS and a screening full field digital mammography (FFDM) on the same day or within the following 30 days of each other

Any women scheduled for screening WBUS and a screening FFDM on the same day or within the following 30 days of each other

For female patients of childbearing potential, all of the following criteria must be met:

Patients with any of the following are not eligible:

Patient is not enrolled on an investigational nonmyeloablative HCT protocol, in which case protocol 2546 serves as an independent primary treatment protocol and the patient must meet the following inclusion and exclusion criteria:

Receipt of locoregional therapy (LRT) with verification of complete response at least 30 days following treatment

Willing to repeat RPFNA at 12 months following initiation of study agent

Have documented or anticipated neutropenia expected to last for at least 7 days, following treatment in at least one of the following clinical situations: acute leukemia, myelodysplasia, severe aplastic anemia, recipients of Autologous hematopoietic stem cell transplant (HSCT), high risk neuroblastoma, advanced stage non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis

Subjects must fit into ONE of the following menopausal categories:\r\n* Premenopausal (n = 40) – defined as meeting all the following criteria:\r\n** Have had at least 8 menstrual cycles in the past 12 months\r\n** Have had no hormonal contraception in the past 3 months prior to registration\r\n** Have serum hormone parameters (estradiol [E2], progesterone, follicle stimulating hormone [FSH]) in premenopausal range on the day of random fine needle aspiration (rFNA); NOTE: subjects will self-report menopausal status at registration, and confirmation of hormonal parameters will occur after registration as part of pre-intervention procedures; if there is mis-assignment of status, the recruitment of future subjects will be adjusted accordingly\r\n* Postmenopausal (n = 40) – defined as meeting all of the following criteria:\r\n** Last menstrual period (LMP) > 1 year previously\r\n** Have had no hormone use in the past 3 months prior to registration\r\n** Serum E2, progesterone, FSH in postmenopausal range on the day of rFNA; NOTE: subjects will self-report menopausal status at registration, and confirmation of hormonal parameters will occur after registration as part of pre-intervention procedures; if there is mis-assignment of status, the recruitment of future subjects will be adjusted accordingly

Patients who have received a single dose of mitomycin C following staging trans-urethral resection (TUR)

Females subjects of childbearing potential (FCBP)1 may participate, providing they meet the following conditions:

Males enrolled into treatment arms receiving CC-122 must: Agree to abstain from donating sperm while taking IP and for at least 3 months following discontinuation of IP

Stable or better disease on re-staging scans following induction mFOLFIRINOX

Pathologic complete response following preoperative chemotherapy

Patients should agree to not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or tremelimumab

Inclusion Criteria:\n\n        Diagnosis and Criteria for Inclusion:\n\n        All patients:\n\n        To be considered eligible to participate in this study, all of the following requirements\n        must be met:\n\n          1. Patient, male or female, is at least 18 years of age.\n\n          2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy\n             or for which standard therapy is not likely to provide meaningful benefit, or patient\n             has refused standard therapy.\n\n          3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n\n          4. Patient is able to take oral medications.\n\n          5. Female patient, if of childbearing potential, has a negative serum pregnancy test\n             within 72 hours prior to taking study drug and agrees to abstain from activities that\n             could result in pregnancy from enrollment through 120 days after the last dose of\n             study treatment, or be of non-childbearing potential. Non-childbearing potential is\n             defined as (by other than medical reasons):\n\n               -  ?45 years of age and has not had menses for > 1 year.\n\n               -  Amenorrheic for < 2 years without a hysterectomy Post hysterectomy, bilateral\n                  oophorectomy, or tubal ligation..\n\n             Note: Abstinence is acceptable if this is the established and preferred contraception\n             for the patient.\n\n          6. Male patient agrees to use an adequate method of contraception starting with the first\n             dose of study treatment through 120 days after the last dose of study treatment..\n\n          7. Patient is able to understand the study procedures and agrees to participate in the\n             study by providing written informed consent.\n\n        Patients with normal hepatic function (Group 1):\n\n        Patients screened for the normal hepatic function group must meet the following additional\n        criteria to be eligible for enrollment:\n\n          1. Patient has no history of hepatic impairment.\n\n          2. Patient has liver function test (LFT) results within normal range:\n\n               -  Total bilirubin ? ULN\n\n               -  Aspartate aminotransferase (AST) ? ULN.\n\n               -  INR ?1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR\n                  is within therapeutic range of intended use of anticoagulants.\n\n          3. Patient has adequate hematologic and renal function as defined below:\n\n               -  Absolute neutrophil count ?1500/µL\n\n               -  Platelets ?100,000/µL\n\n               -  Hemoglobin ?9 g/dL\n\n               -  Serum creatinine ?1.5 × ULN or a calculated creatinine clearance ?60 mL/min using\n                  the Cockcroft-Gault equation.\n\n        Patients with moderate hepatic impairment (Group 2):\n\n        Patients screened for the moderate hepatic impairment group must meet the following\n        additional criteria to be eligible for enrollment:\n\n          1. Patient has stable, moderate hepatic impairment, defined as:\n\n               -  BILI: >1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1\n\n               -  AST: Any value\n\n               -  INR less than 1.8 unless the patient is receiving anticoagulant therapy and the\n                  INR is within therapeutic range of intended use of anticoagulants.\n\n          2. Patient has hematologic and renal function as defined below:\n\n               -  Absolute neutrophil count ?1000/µL\n\n               -  Platelets ?75,000/µL\n\n               -  Hemoglobin ?8 g/dL\n\n               -  Serum creatinine ?1.5 × ULN or a calculated creatinine clearance ?60 mL/min using\n                  the Cockcroft-Gault equation.\n\n          3. Patient's hepatic disease is deemed stable by the Investigator\n\n        Criteria for Exclusion:\n\n        Patients will not be eligible for study entry if any of the following criteria are met:\n\n        All patients:\n\n          1. Patient has undergone palliative radiotherapy within 1 week of study drug\n             administration, encompassing >20% of the bone marrow.\n\n          2. Patient is starting chemotherapy within 3 weeks of study drug administration.\n\n          3. Patient has a known hypersensitivity to the components of niraparib or excipients\n\n          4. Patients who received colony-stimulating factors within 2 weeks prior to the first\n             dose of study treatment are not eligible.\n\n          5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for\n             neuropathy, alopecia or fatigue.\n\n          6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.\n\n          7. Patient has undergone major surgery within 3 weeks of starting the study or patient\n             has not recovered from any effects of any major surgery.\n\n          8. Patient is considered a poor medical risk due to a serious, uncontrolled medical\n             disorder (other than hepatic impairment) or active, uncontrolled infection.\n\n          9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of\n             receiving niraparib.\n\n         10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving\n             study treatment or for 3 months after the last dose of study treatment.\n\n         11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid\n             leukemia (AML).\n\n             NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the\n             study.\n\n         12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to\n             dosing until the time of the last PK blood draw, any of the following cytochrome (CYP)\n             1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and\n             theophylline.\n\n         13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within\n             4 days of the first administration of niraparib until the final PK sample collection.\n\n         14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to\n             dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp)\n             inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin,\n             conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine,\n             itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine,\n             ticagrelor and verapamil.\n\n         15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers\n             within 48 hours prior to niraparib administration, and/or within 6 hours after\n             niraparib administration.\n\n         16. Patient has esophagogastrointestinal disease or resection that is likely to interfere\n             with the absorption of niraparib.\n\n        Patients with moderate hepatic impairment (Group 2):\n\n        Patients screened for the moderate hepatic impairment group who meet any of the following\n        additional criteria will be excluded from the study:\n\n          1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic\n             shunt.\n\n          2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the\n             investigator within the screening period.\n\n          3. Patient has acute liver disease caused by drug toxicity or by an infection.\n\n          4. Patient has biliary obstruction or other causes of hepatic impairment not related to\n             parenchymal disorder and/or disease of the liver.\n\n          5. Patient has esophageal variceal bleeding within the past 2 months.\n\n          6. Patient is receiving anticoagulant therapy with warfarin or related coumarins.\n\n          7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic\n             coma.

Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ? 2 years with the exception of the following non-invasive malignancies:

Use of the following:

Exposure to any of the following:

Subject is planned to undergo either of the following:

Subject has one of the following underlying diseases:

hospitalized with one of the following

Cohort B only: (N = 5 evaluable patients): Planned nephrectomy within 12 weeks following protocol scan

At least one of the following:

Individuals who have any of the following will not be eligible to participate:

If the patient is a survivor of a prior invasive cancer, all of the following criteria must apply: *Patient has undergone potentially curative therapy for all prior malignancies \r\n*No evidence of active/recurrent disease within 5 years

Participants with thyroid carcinoma or thyroid disease for whom systemic radioactive iodine therapy is part of planned diagnostic work-up or treatment within 2 months following the contrast mammogram study

Participants who do not have residual calcifications present on mammogram following biopsy

Treatment with any of the following:

Abnormal c-MET dysregulation, defined as the following from archival historical results of molecular pre-screening evaluations.

the use of one of the following: diaphragm, Lea's shield, FemCap, sponge, and

Patients are to be excluded from the study if they have any of the following:

Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject has eligible disease status:\n\n               1. Newly diagnosed and are undergoing induction therapy prior to undergoing first\n                  Autologous stem cell transplant (ASCT) or\n\n               2. Myeloma patients with prior relapse undergoing first ASCT. or\n\n               3. Myeloma patients with relapsed disease after first ASCT who are undergoing second\n                  ASCT. Subjects must have achieved at least a partial response (PR) prior to\n                  proceeding to ASCT.\n\n          2. Subject is > 18 and ? 70 years of age at the time of signing the informed consent form\n             (ICF).\n\n          3. Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          4. Subject is willing and able to adhere to the study schedule and other protocol\n             requirements.\n\n          5. Performance status of Karnofsky performance status ? 70% or Eastern Cooperative\n             Oncology Group (ECOG) < 2\n\n          6. Ability to be off immunosuppressive drugs for at least 3 days prior to the PNK-007\n             cell infusion. Steroids at the equivalent of no more than 5 mg prednisone per day are\n             permissible.\n\n          7. Be a candidate for ASCT based on institutional practices.\n\n          8. Subjects must have autologous peripheral blood stem cell graft available in storage\n             for additional transplant in the event of engraftment failure.\n\n          9. Female of childbearing potential (FCBP) must:\n\n               1. Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after the end of study treatment. This applies even if\n                  the subject practices true abstinence* from heterosexual contact.\n\n               2. Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed at applicable study visits and source documented) or agree to use, and\n                  be able to comply with, effective contraception without interruption, during the\n                  study therapy (including dose interruptions), and for 28 days after\n                  discontinuation of PNK-007.\n\n                  A female of childbearing potential (FCBP) is a female who:\n\n                  1) has achieved menarche at some point, 2) has not undergone a hysterectomy or\n                  bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea\n                  following cancer therapy does not rule out childbearing potential) for at least\n                  24 consecutive months (ie, has had menses at any time in the preceding 24\n                  consecutive months).\n\n         10. Male subjects must:\n\n               1. Practice true abstinence* (which must be reviewed at applicable study visits) or\n                  agree to use a condom during sexual contact while participating in the study,\n                  during dose interruptions and for at least 28 days following PNK-007\n                  discontinuation, even if he has undergone a successful vasectomy. * True\n                  abstinence is acceptable when this is in line with the preferred and usual\n                  lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation,\n                  symptothermal, post ovulation methods] and withdrawal are not acceptable methods\n                  of contraception]).\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Subject has plasma cell leukemia.\n\n          2. Subject has non-secretory myeloma.\n\n          3. Subject has previously undergone allogeneic stem cell transplant.\n\n          4. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n          5. Subject has any condition including the presence of laboratory abnormalities which\n             places the subject at unacceptable risk if he or she were to participate in the study.\n\n          6. Subject has any condition that confounds the ability to interpret data from the study.\n\n          7. Subject has a body weight exceeding 120 kg.\n\n          8. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or\n             alkaline phosphatase ? 2.5 x the upper limit of normal (ULN) at screening.\n\n          9. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening\n             calculated using the Modification of Diet in Renal Disease Study equation.\n\n         10. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease)\n             at screening.\n\n         11. Subject has had prior treatment with biologic antineoplastic agents no less than 7\n             days before PNK-007 infusion and at least 5 half-lives. For agents that have known AEs\n             occurring beyond 7 days after administration (ie, monoclonal antibodies), this period\n             must be extended beyond the time during which acute AEs are known to occur.\n\n         12. Subject is pregnant or breastfeeding.\n\n         13. Subject has new or progressive pulmonary infiltrates or pleural effusion large enough\n             to be detected by chest x-ray or computed tomography (CT) scan.\n\n         14. Subject has active autoimmune disease other than controlled connective tissue disorder\n             or those who are not on active therapy.\n\n         15. Subject has human immunodeficiency virus (HIV) are excluded due to increased risk of\n             lethal infections when treated with myeloablative chemotherapy.\n\n         16. Subject has history of malignancy, other than multiple myeloma (MM), unless the\n             subject has been free of disease for > 3 years from the date of signing the ICF.\n             Exceptions include the following:\n\n               1. Basal cell carcinoma of the skin\n\n               2. Squamous cell carcinoma of the skin\n\n               3. Carcinoma in situ of the cervix\n\n               4. Carcinoma in situ of the breast\n\n               5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)\n\n         17. Subject has a history of severe asthma and is presently on chronic medications or has\n             a history of other symptomatic pulmonary disease.\n\n         18. Untreated chronic infection or treatment of any infection with systemic antibiotics\n             within 2 weeks prior to melphalan.\n\n         19. Subject has any other organ dysfunction that will interfere with the administration of\n             the therapy according to this protocol.\n\n         20. Subject has a resting left ventricular ejection fraction (LVEF) of < 35% obtained by\n             echocardiography or multigated acquisition scan (MUGA).\n\n         21. Subject was treated with an investigational product no less than 28 days before\n             PNK-007 infusion. Subject must no longer be a participant in the previous\n             interventional study at the time of the PNK-007 infusion.

Cohort A only (N = 5 evaluable patients):- Planned radical prostatectomy within 12 weeks following protocol scan

If the patient is a survivor of a prior invasive cancer, all of the following criteria must apply: \r\n* Patient has undergone potentially curative therapy for all prior malignancies\r\n* No evidence of active/recurrent disease

Vitamin B12, folate or vitamin A deficiency. Rescreening following repletion therapy is acceptable.

Must meet at least 1 of the following 3 criteria for progressive metastatic disease, according to Prostate Cancer Working Group 2 (PCWG2) criteria:

Seeing a participating physician for less than a year and expecting to see this physician at least once in the following year

The patient must have one negative cystoscopy 3 months following most recent biopsy

Inclusion Criteria:\n\n        Subjects who meet all of the following criteria may be enrolled in this Study:\n\n          1. Subject is male or female, age 18 or older.\n\n          2. Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n             lesions suspicious for lung cancer.\n\n          3. Subject's pulmonary nodule or lesion is greater than 4mm. Size is determined by the\n             largest nodule or lesion dimension identified from CT imaging.\n\n          4. Subject meets one or more of the following conditions:\n\n               -  indicated for a tissue biopsy\n\n               -  indicated for surgical resection of the lung\n\n          5. Subject must be able to receive a ProLung Test\n\n               -  within 60 days of abnormal CT (Inclusion Criterion 2 & 3)\n\n               -  within 60 days prior to the tissue biopsy or surgical resection (Inclusion\n                  Criterion 4).\n\n          6. Subject is capable of understanding and agreeing to fulfill the requirements of this\n             Protocol.\n\n          7. Subject has signed the IRB/IEC approved Informed Consent Form (\ICF\).\n\n        Exclusion Criteria\n\n        The following criteria will disqualify a subject from enrollment into this Study:\n\n          1. Subject has an implanted electronic device in the chest.\n\n          2. Subject receiving therapy for suspected chest infection such as fungal infection or\n             tuberculosis.\n\n          3. Subject with diagnosed malignancy other than lung cancer, non-melanoma skin cancer or\n             any cancer in which the Principal Investigator does not suspect metastatic disease to\n             the lung, who has 2 or more suspicious pulmonary nodules.\n\n          4. Subject has received an invasive medical or surgical procedure within the thoracic\n             cavity within 30 days prior to the ProLung Test or within the previous 14 days for a\n             bronchoscopic procedure.\n\n          5. Subject presents with an anomalous physical or anatomical condition that precludes\n             ProLung Test measurement.\n\n          6. Subject will have undergone unusually strenuous exercise within 24 hours.\n\n          7. Subject who has significant systemic diseases such as uncontrolled diabetes, advanced\n             heart failure, or a recent myocardial infarction, or other medical condition such as\n             severe morbid obesity that in the judgment of the Principal Investigator would make\n             him/her unsuitable for the Study.

Inclusion Criteria:\n\n        Subjects who meet all of the following criteria may be enrolled in this Study:\n\n          1. Subject is male or female, age 18 or older.\n\n          2. Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n             lesions suspicious for lung cancer.\n\n          3. Subject's pulmonary nodule or lesion is greater than 4mm. Size is determined by the\n             largest nodule or lesion dimension identified from CT imaging.\n\n          4. Subject meets one or more of the following conditions:\n\n               -  indicated for a tissue biopsy\n\n               -  indicated for surgical resection of the lung\n\n          5. Subject must be able to receive a ProLung Test\n\n               -  within 60 days of abnormal CT (Inclusion Criterion 2 & 3)\n\n               -  within 60 days prior to the tissue biopsy or surgical resection (Inclusion\n                  Criterion 4).\n\n          6. Subject is capable of understanding and agreeing to fulfill the requirements of this\n             Protocol.\n\n          7. Subject has signed the IRB/IEC approved Informed Consent Form (\ICF\).\n\n        Exclusion Criteria\n\n        The following criteria will disqualify a subject from enrollment into this Study:\n\n          1. Subject has an implanted electronic device in the chest.\n\n          2. Subject receiving therapy for suspected chest infection such as fungal infection or\n             tuberculosis.\n\n          3. Subject with diagnosed malignancy other than lung cancer, non-melanoma skin cancer or\n             any cancer in which the Principal Investigator does not suspect metastatic disease to\n             the lung, who has 2 or more suspicious pulmonary nodules.\n\n          4. Subject has received an invasive medical or surgical procedure within the thoracic\n             cavity within 30 days prior to the ProLung Test or within the previous 14 days for a\n             bronchoscopic procedure.\n\n          5. Subject presents with an anomalous physical or anatomical condition that precludes\n             ProLung Test measurement.\n\n          6. Subject will have undergone unusually strenuous exercise within 24 hours.\n\n          7. Subject who has significant systemic diseases such as uncontrolled diabetes, advanced\n             heart failure, or a recent myocardial infarction, or other medical condition such as\n             severe morbid obesity that in the judgment of the Principal Investigator would make\n             him/her unsuitable for the Study.

Patients eligible for this companion sample collection protocol must not meet any of the exclusion criteria in the CLEE011A2404 study, in addition to the following:

Key Inclusion Criteria Includes:\n\n        Patients meeting all of the following criteria may be enrolled in the study:\n\n          1. Must be able to understand and voluntarily sign an ICF.\n\n          2. Must be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy\n             (REMS)™ program, and be willing and able to comply with the requirements of the\n             POMALYST REMS™ program (Appendix 9.3).\n\n          3. Must be ? 18 years of age at the time of signing the ICF.\n\n          4. Must be able to adhere to the study visit schedule and other protocol requirements.\n\n          5. Must have a documented diagnosis of MM and have relapsed or relapsed and refractory\n             disease. Patients must have received at least 2 lines of prior therapies. Patients\n             must have relapsed after having achieved at least stable disease for at least 1 cycle\n             of treatment to at least 1 prior regimen and then developed PD. Relapsed and\n             relapsed-and-refractory patients must have documented evidence of PD during or within\n             60 days (measured from the end of the last cycle) of completing treatment with the\n             last antimyeloma drug regimen used just prior to study entry.\n\n          6. Patients must have undergone prior treatment with at least 2 cycles of lenalidomide\n             and at least 2 cycles of a proteasome inhibitor (either in a separate regimen or\n             within the same regimen.\n\n          7. Must not be a candidate for autologous stem cell transplant (ASCT), have declined the\n             option of ASCT, or have relapsed after prior ASCT.\n\n          8. Must have measurable levels of myeloma paraprotein in serum (? 0.5 g/dL) or urine (?\n             0.2 g/24 hours). Patients who do not have myeloma paraprotein must have serum free\n             light chain (SFLC) concentration of ? 10 mg/dL, provided SFLC ratio is abnormal.\n             Nonsecretory myeloma is excluded.\n\n          9. Must have Eastern Cooperative Oncology Group performance status score of 0, 1, or 2.\n\n         10. Females of childbearing potential must have a negative serum or urine pregnancy test\n             as described in Appendix 9.3 for the POMALYST REMS™ program. Females of childbearing\n             potential and males must either commit to continued abstinence from heterosexual\n             intercourse or must abide by birth control requirements as described in Appendix 9.3\n             for the POMALYST REMS™ program.\n\n         11. Must agree to refrain from donating blood while on study drug and for 28 days after\n             discontinuation from this study.\n\n         12. Must agree not to share study medication with another person.\n\n         13. Must be able to take ASA (81 or 325 mg) daily as prophylactic anticoagulation.\n             Patients intolerant to ASA may use low molecular weight heparin. Lovenox is\n             recommended. Coumadin will be allowed provided the patient is fully anticoagulated,\n             with an international normalized ratio of 2 to 3.\n\n        Key Exclusion Criteria Includes:\n\n        Patients meeting any of the following criteria will be excluded from enrollment in the\n        study:\n\n          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the patient from signing the ICF or from following the study\n             requirements.\n\n          2. Pregnant or lactating females.\n\n          3. Prior therapy with histone deacetylase inhibitor or pomalidomide.\n\n          4. Any of the following laboratory abnormalities:\n\n               -  ANC < 1,000/µL\n\n               -  Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated\n                  cells are plasma cells, or a platelet count < 50,000 for patients in whom ? 50%\n                  of bone marrow nucleated cells are plasma cells\n\n               -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or\n                  recombinant human erythropoietin use is permitted).\n\n               -  Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If\n                  creatinine clearance calculated from the 24 hour urine sample is ? 45 mL/min,\n                  patient will qualify for the trial.\n\n               -  Serum glutamic oxaloacetic transaminase/aspartate aminotransferase, or serum\n                  glutamic pyruvic transaminase/alanine aminotransferase > 3.0 × ULN\n\n               -  Serum total bilirubin > 2.0 mg/dL\n\n          5. Prior history of malignancies, other than MM, unless the patient has been free of the\n             disease for ? 3 years. Exceptions include the following:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Ductal carcinoma in situ; or cervical intraepithelial neoplasia\n\n               -  Carcinoma of the prostate with a current prostate-specific antigen below the\n                  upper limit of normal\n\n          6. Corrected QT interval (QTc) using Fridericia's formula value > 480 msec at Screening;\n             family or personal history of long QTc syndrome or ventricular arrhythmias including\n             ventricular bigeminy at Screening; previous history of drug-induced QTc prolongation\n             or the need for treatment with medications known or suspected of producing prolonged\n             QTc intervals on electrocardiogram.\n\n          7. Known human immunodeficiency virus, hepatitis B virus, and known or suspected active\n             hepatitis C virus infection.\n\n          8. Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone (such as\n             Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically\n             managed is allowable.\n\n          9. Peripheral neuropathy ? Grade 2 despite supportive therapy.\n\n         10. Radiotherapy or systemic therapy (standard or an investigational or biologic\n             anticancer agent) within 14 days of initiation of study drug treatment.\n\n         11. Current enrollment in another clinical trial involving treatment and/or receiving an\n             investigational agent for any reason.\n\n         12. Inability or unwillingness to comply with birth control requirements or any of the\n             POMALYST REMS™ requirements per Appendix 9.3.

Use of a combination of any two of the following:

TKI treatment failure will be defined as 1 of the following:

Intolerance to TKI therapy will be defined as 1 of the following:

For inclusion in the study as a patient with hepatic impairment, the following criterion\n        must be met:\n\n        1. Patients must have stable chronic hepatic impairment for at least 2 weeks prior to Day\n        1, see Section 4.1.1. Patients with hepatic metastases and/or HCC are eligible for the\n        study, providing the hepatic metastases or HCC are not the sole reason for any changes in\n        liver function satisfying the criteria for mild or moderate hepatic impairment as defined\n        by the Child Pugh criteria. Patients must have globally impaired hepatic function to\n        participate in the study.\n\n        For inclusion in the study as a patient with normal hepatic function, the following\n        criteria must be met:\n\n          1. Negative result for serum hepatitis B surface antigen and hepatitis C antibody\n\n          2. Total bilirubin less than or equal to1.5 x institutional ULN, albumin and prothrombin\n             time within normal limits and must not have ascites (unless related to disease under\n             study) or encephalopathy.\n\n          3. AST and ALT less than or equal to2.5 x institutional ULN unless liver metastases are\n             present in which case it must be less than or equal to5 x ULN.\n\n        All patients must fulfil the following criteria:\n\n          1. Male or female, aged at least 18 years.\n\n          2. Histological or, where appropriate, cytological confirmation of any malignant solid\n             tumour refractory or resistant to standard therapy or for which no suitable effective\n             standard therapy exists. Tumours in which inhibition of the EGFR pathway is considered\n             relevant by the Investigator are not mandated but are encouraged.\n\n          3. ECOG performance status less than or equal to2.\n\n          4. Patients must have a life expectancy of greater than or equal to12 weeks, as estimated\n             at the time of screening.\n\n          5. Females should be using adequate contraceptive measures and must have a negative\n             pregnancy test prior to start of dosing if of child-bearing potential or must have\n             evidence of non-child-bearing potential by fulfilling one of the following criteria at\n             screening: post-menopausal defined as aged more than 50 years and amenorrhoeic for at\n             least 12 months following cessation of all exogenous hormonal treatments; women under\n             50 years old would be consider postmenopausal if they have been amenorrheic for 12\n             months or more following cessation of exogenous hormonal treatments and with LH and\n             FSH levels in the postmenopausal range for the institution; documentation of\n             irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or\n             bilateral salpingectomy but not tubal ligation\n\n          6. Male patients should be willing to use barrier contraception, ie, condoms, until 6\n             months after last study drug is taken.\n\n        Exclusion criteria:\n\n          1. Participation in another clinical study with an IP during the last 14 days (or a\n             longer period depending on the defined characteristics of the agents used).\n\n          2. Treatment in the previous 3 months before dosing in this study with any drug known to\n             have a well-defined potential for fulminant hepatotoxicity (eg, halothane and\n             methotrexate).\n\n          3. Treatment with any of the following: an EGFR TKI w/in 8 days or approximately 5x\n             half-life, whichever is the longer, of the first dose of study treatment; Any\n             cytotoxic chemotherapy, investigational agents or other anticancer drugs w/in 14 days\n             of the first dose of study treatment; Major surgery (excluding placement of vascular\n             access) w/in 4 weeks of the first dose; Radiotherapy with a limited field of radiation\n             for palliation within 1 week of the first dose of study treatment, with the exception\n             of patients receiving radiation to more than 30% of the bone marrow or with a wide\n             field of radiation which must be completed within 4 weeks of the first dose of study\n             treatment; Patients currently receiving (or unable to stop use prior to receiving the\n             first dose of study treatment) medications or herbal supplements known to be potent\n             inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3\n             week prior) (Appendix H). All patients in Part B and continued access must try to\n             avoid concomitant use of any medications, herbal supplements and/or ingestion of foods\n             with known potent inducer/inhibitory effects on CYP3A4 (Appendix H).\n\n          4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\n             starting study treatment with the exception of alopecia and Grade 2 prior\n             platinum-therapy related neuropathy.\n\n          5. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,\n             or other products containing grapefruit or Seville oranges within 7 days of the first\n             administration of the IP until final PK sample collection on Day 22.\n\n          6. Spinal cord compression or brain metastases unless asymptomatic, stable and not\n             requiring steroids for at least 4 weeks prior to start of study treatment.\n\n          7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension and active bleeding diatheses, which in the Investigator's opinion makes\n             it undesirable for the patient to participate in the study or which would jeopardise\n             compliance with the protocol, or active infection including hepatitis B, hepatitis C\n             and human immunodeficiency virus (HIV). Screening for chronic conditions is not\n             required.\n\n          8. Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following laboratory values: ANCless than1.5x10.9/L; platelet count less\n             than100x10.9/L; haemoglobinless than90 g/L; Creatinine greater than1.5 x institutional\n             ULN concurrent with creatinine clearance less than50 mL/min (measured or calculated by\n             Cockcroft-Gault formula); confirmation of creatinine clearance is only required when\n             creatinine is greater than1.5 x institutional ULN.\n\n          9. Any of the following cardiac criteria: Mean resting corrected QT interval corrected\n             for heart rate using Fridericia's correction factor (QTcF) greater than470 msec\n             obtained from 3 ECGs; Any clinically important abnormalities in rhythm, conduction or\n             morphology of resting ECG eg, complete left bundle branch block, third degree heart\n             block, second degree heart block, PR interval greater than250 msec; Any factors that\n             increase the risk of QTc prolongation or risk of arrhythmic events such as heart\n             failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome\n             or unexplained sudden death under 40 years of age or any concomitant medication known\n             to prolong the QT interval.\n\n         10. Patients unable to swallow oral medication or patients with GI disorders or\n             significant GI resection likely to interfere with the absorption of AZD9291.\n\n         11. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation\n             pneumonitis which required steroid treatment, or any evidence of clinically active\n             ILD.\n\n         12. Women who are breastfeeding.\n\n         13. Patients with a known hypersensitivity to AZD9291 or any of its excipients. Patients\n             with normal hepatic function should not have a history or presence of hepatic disease\n             known to interfere with the absorption, distribution, metabolism or excretion of\n             AZD9291.\n\n        Patients with mild or moderate hepatic function should not enter if the following are\n        fulfilled:\n\n          1. Patients with hepatic encephalopathy within the last 4 weeks prior to Day 1.\n\n          2. Fluctuating or rapidly deteriorating hepatic function as indicated by widely varying\n             or worsening of clinical and/or laboratory signs of hepatic impairment within the\n             screening period.\n\n          3. Presence of acute liver disease caused by drug toxicity or by an infection.\n\n          4. Severe portal hypertension or surgical porto-systemic shunts.\n\n          5. Biliary obstruction or other causes of hepatic impairment not related to parenchymal\n             disorder and/or disease of the liver.\n\n          6. Oesophageal variceal bleeding within the past 2 months.\n\n          7. Anticoagulant therapy with warfarin or related coumadine.NOTE: Preferred format\n             includes lists of inclusion and exclusion criteria

Use or consumption of any of the following substances:

Chemotherapy-refractory disease, defined as one or more of the following:

Use or consumption of any of the following substances:

Diagnosis of 1 of the following diseases:

Measurable disease meeting the following criteria and confirmed by central radiographic review:

Participants must be Iodine-131 refractory/resistant as defined by at least one of the following: