Participants must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; participants with uncontrolled Kaposi sarcoma are permitted (KS must be increasing despite HAART and HIV suppression for greater than or equal to 2 months, or stable KS despite HAART for greater than or equal to 3 months)\r\n* For participants in the 24 participant solid tumor cohort, only those histologies not known to respond to single agent nivolumab (such as pancreas, prostate, and microsatellite stable [MSS] colorectal cancer) will be excluded\r\n* For participants in the relapsed refractory HIV-cHL expansion cohort, participants must have histologically confirmed, relapsed/refractory (defined as relapsed/refractory to one or greater lines of therapy) HIV-associated classical Hodgkin lymphoma
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard Food and Drug Administration (FDA)-approved systemic curative or palliative antitumor therapies do not exist or are no longer effective or for which MK-3475 (pembrolizumab) is FDA-approved as standard of care therapy
Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:\r\n* Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR\r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival\r\n* NOTE: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage I or II cancer from which the patient is currently in complete remission; any other cancer from which the patient has been disease-free for 5 years
Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR \r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
No waiting period for patients who relapse while receiving standard maintenance therapy
For patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy
Eligible for standard induction chemotherapy according to their treating physician
Patient must meet at least one of the following criteria: a. Progressed or recurrent despite standard therapy, b. No standard therapy exists for this malignancy, c. Patient is intolerant of standard therapy, d. Patient is not a candidate for standard therapy, e. For AML and MDS patients: patient is not a candidate for allogeneic hematopoietic stem cell transplantation, f, For sarcoma patients: f-1. Patient has disease that is metastatic or unresectable, f-2. Patient with metastatic disease has had at least one prior line of therapy for metastatic disease, f-3. No curative multimodality options exist
Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
Part A and A2: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit
Part B: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit and/or participants must have progressed after at least 1 prior chemotherapy regimen in the metastatic setting, and for which carboplatin (for Part B1), gemcitabine (for Part B2), or cisplatin (for Part B3) would be considered standard of care.
Neuroblastoma- Patients that have relapsed following standard of care therapy (such as high risk patients, patient presenting after age 15 months or MYCN amplified, and only following (for eligible patients) high-dose chemotherapy followed by hematopoietic stem cell transplantation and maintenance therapy with retinoic acid and antibody therapy) or having progressed during standard of care therapy and non-responsive/progressive to accepted curative chemotherapy.
Medulloblastomas (At relapse after standard of care therapy [surgery, chemotherapy and/or radiation] and/or non-responsive/progressive on accepted curative therapy)
Gliomas (At relapse after standard of care therapy [surgery and/or radiation and/or chemotherapy] and/or non-responsive/progressive on accepted curative therapy)
Ependymomas (At relapse after standard of care therapy [surgery with or without radiation] and/or non-responsive/progressive on accepted curative therapy)
Choroid plexus tumors (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
Craniopharyngiomas (At relapse after standard of care therapy [surgery or suppressive therapy] and/or non-responsive/progressive on accepted curative therapy)
Dysembryoplastic neuroepithelial tumors (DNETs) (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
Meningiomas (At relapse after standard of care therapy [surgery] and/or non-responsive/progressive on accepted curative therapy)
Primitive Neuroectodermal Tumors (PNETs) (At relapse after standard of care therapy [surgery, chemotherapy, and/or radiation] and/or non-responsive/progressive on accepted curative therapy)
Germ cell tumors (At relapse after standard of care therapy [surgery, and/or radiation and/or chemotherapy] and/or non-responsive/progressive on accepted curative therapy)
Renal Wilms tumor (At relapse after standard of care therapy [surgery, and/or radiation, chemotherapy] and/or non- responsive/progressive to accepted chemotherapy) Renal cell carcinoma (At relapse after standard of care therapy [surgery, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy) Malignant rhabdoid tumor (At diagnosis, as there is no known curative therapy) Clear Cell Sarcoma- (At relapse after standard of care therapy [radiation, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy) Germ Cell tumors (At relapse after standard of care therapy [surgery, chemotherapy] and/or non-responsive/progressive to accepted curative chemotherapy)
Liver Tumors (At relapse after standard of care therapy [surgery, chemotherapy] and/or non- responsive/progressive to accepted curative chemotherapy)
Histologically or cytologically proven diagnosis of prostate cancer, sqNSCLC, TNBC, or known PTEN-deficient solid malignancy, and is refractory to standard therapies.
2. Part A, must have a histologically or cytologically documented, incurable, or metastatic solid tumor that has progressed on, or been intolerant to, all standard systemic therapy options for the tumor type in the metastatic setting, or must have a tumor type for which no such standard systemic option exists;
Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
Patients who, in the judgment of their treating physician, have available standard of care therapies will be excluded
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists
HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available
Diagnosis of advanced/metastatic solid malignancy for which no standard treatment option exists that will confer clinical benefit
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy
Patients who are women of childbearing potential must have a negative pregnancy test documented =< 14 days prior to registration; this is not specific to dose escalation and is mandatory for standard care for patients being treated with radiation therapy; the cost of this test will be covered by standard of care
Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy
Histologically confirmed diagnosis of advanced unresectable or metastatic STS, not amenable to curative treatment and after available standard therapies have failed to provide clinical benefit. Note: Participants with a diagnosis of Grade 1 liposarcoma (atypical lipomatous neoplasms) are eligible if there is histological or radiographic evidence of evolution to more aggressive disease.
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.
1. Written informed consent must be obtained prior to any screening procedures\n\n          2. Male or female patients ? 18 years of age who present with one of the following:\n\n             Arms 1-3:\n\n               -  Refractory/relapsed AML following ?1 prior therapies and are deemed by the\n                  investigator not to be candidates for standard therapy, including re-induction\n                  with cytarabine or other established chemotherapy regimens for patients with AML\n                  (patients who are suitable for standard re-induction chemotherapy or\n                  hematopoietic stem cell transplantation and willing to receive it are excluded)\n\n               -  De novo AML patients who are suitable for treatment with decitabine (patients who\n                  are suitable for standard induction chemotherapy or hematopoietic stem cell\n                  transplantation and willing to receive it are excluded)\n\n               -  High risk MDS (patients who are suitable for standard re-induction chemotherapy\n                  or hematopoietic stem cell transplantation and willing to receive it are\n                  excluded)\n\n             Arms 4-5:\n\n               -  Refractory / relapsed AML following ?1 prior therapies (Arms 4a & 5a)\n\n               -  High risk MDS who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note:\n                  hypomethylating agent failure is defined as progressive disease on\n                  hypomethylating agent therapy or lack of clinically meaningful response as deemed\n                  by investigator after at least 4 cycles of hypomethylating agent therapy.)\n\n          3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n          4. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to\n             the institutions guidelines and be willing to undergo a bone marrow aspirate\n             and/biopsy at screening, during and at the end of therapy on this study. Exceptions\n             may be considered after documented discussion with Novartis.\n\n          5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by\n             the investigator and as per local decitabine package insert.
PART I: participants must have histologically confirmed malignancy that is metastatic or unresectable and resistant to standard therapy or for which no standard therapy is available
Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.
Progressed following all standard of care therapies for advanced breast cancer. OR
Patients must be candidates for standard of care treatment consisting of chemotherapy (cisplatin) and radiation
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available. Patients must fit into one of the following groups:
Disease that has progressed on standard therapy or for whom there is no other therapy option available
Histologically or pathologically confirmed malignancy (hematologic or solid tumor) that is metastatic or unresectable and for which standard of care therapy does not exist or is no longer effective
COHORT 2: Is eligible for treatment with a standard cytarabine and anthracycline or similar intensive induction chemotherapy, or is willing to receive intensive induction therapy; if subject is not considered eligible for treatment with standard or similar intensive induction chemotherapy due to comorbidities or other factors, or is unwilling to receive intensive induction therapy will be allowed to participate in this study
Patients without a curative therapy or whose tumor does not have standard chemotherapy
Received standard of care treatment for primary malignancy and standard of care treatment for relapsed cancer
Patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer.
Have documented relapse or refractoriness after at least 1 line (MB and ARMS subjects) or 2 lines (NB and ES subjects) of standard-of-care therapy, including each of the following:
Pathologically-confirmed, locally advanced or metastatic solid tumors that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment (Dose Escalation Phase)
Histologically-diagnosed, advanced Gl tumors that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment (Dose Expansion Phase)
Histologically-diagnosed advanced colorectal tumors that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment (Phase 1b)
Diagnosis of tumor type with the potential to have P-cadherin expression that is resistant to standard therapy or for which no standard therapy is available
Dose escalation phase only: Subject not responding to standard therapy or for whom no standard treatment exists
Dose expansion phase: Subject not responding to standard therapy or for whom no standard treatment exists with:
Patients who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option; eligible patients should not have available therapies that will convey clinical benefit
Documented radiographic or clinical disease progression on no more or less than one previous line of standard therapy
Patients must have a histologically confirmed nonhematological, metastatic or locally advanced, incurable malignancy for which paclitaxel is clinically appropriate. Patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible.
Single agent (SA) Dose Escalation: Histologically or cytologically proven acute leukemia or high-risk MDS as defined by the World Health Organization (WHO) criteria and IPSS-R, respectively, that is relapsed or refractory (R/R) to standard therapy or for whom standard treatments are contraindicated, OR
AML SA expansion group 1: histologically or cytologically proven AML with a FLT3 ITD or TKD mutation previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated
AML SA expansion group 2: histologically or cytologically proven AML with intermediate or unfavorable risk cytogenetics in the absence of a detectable FLT3 ITD or TKD mutation as previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated
AML/MDS combination treatment (dose escalation and expansion): histologically or cytologically proven AML or MDS as defined by WHO criteria and IPSS-R, respectively, that is: R/R to standard therapy, or AML: who are unfit for, or unwilling to receive standard induction therapy, or MDS: eligible to receive azacitidine
Histological documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Subjects should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Subjects whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority approved appropriate targeted therapy for their tumor types before enrollment.
Histopathologically confirmed diagnosis of an advanced solid tumor such as breast cancer or midline carcinoma with NUT rearrangement, that has progressed despite standard therapy, or for which no standard therapy exists. For enrollment in the expansion cohorts, histopathological confirmation of triple-negative breast cancer or high-grade serous ovarian cancer is required.
Pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
Histologic evidence of advanced solid tumors (excluding central nervous system (CNS) primary tumors) non-resectable, refractory to standard therapies, or patient cannot receive or refuses standard therapy.
Patients with AML refractory to primary induction chemotherapy, relapsed disease, or age >= 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
Histologically confirmed triple negative breast cancer that are refractory, intolerant, or ineligible to receive approved standard therapies
have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or
no longer be candidates for standard therapy or
have tumors for which there is no standard therapy
Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available. Subjects with melanoma who are ineligible to receive or have declined ipilimumab treatment, or who are refractory or intolerant to ipilimumab may enroll.
Patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have histopathologically /cytologically confirmed advanced solid tumor which is refractory to standard therapeutic options, or for which there are no standard therapeutic options, or for whom paclitaxel is an appropriate palliative treatment option (patients for whom paclitaxel or nab-paclitaxel are established treatment options with a proven survival benefit in first line will be excluded)
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Have a histologically confirmed diagnosis of an advanced solid tumor or lymphoma that has progressed in spite of at least one prior line of treatment, and for which additional effective standard therapy is not available. For this study, effective standard therapy is defined as treatment that has been shown to be curative and/or to prolong survival. In addition, subjects who are considered to not be candidates for standard therapy or who decline standard therapy are eligible for this study; in such cases, documentation of the reason for omitting or declining a standard therapy is required.
A patient with low grade glioma who has failed standard therapy
Received 1 or 2 prior standard of care regimens for advanced or metastatic disease
Failure of, inability to, or refusal to receive standard of care.
Participant must have metastatic CRPC or AML not amenable to curative therapy, refractory to standard of care therapy or for which standard of care therapy does not exist. Participants with AML who are candidates for stem cell transplantation must have been offered this therapeutic option. Must meet additional criteria specific for each diagnosis, metastatic CRPC and relapsing/remitting AML, as described in the protocol.
Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed following at least one line of therapy and no other standard therapy with proven clinical benefit is available
At least one line of prior combination and no other standard therapy with proven clinical benefit is available.
Must have received at least one prior line chemotherapy regimen and no other standard therapy with proven clinical benefit is available.
Histologically or cytologically confirmed solid tumors of the types specified below, with incurable, locally advanced or metastatic disease that has failed standard therapy or for which no standard treatment option exists. For Ovarian Cancer
Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.
Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.
Histologically or cytologically confirmed advanced TNBC that is relapsed, refractory, or progressive and not eligible for another standard therapy that would confer clinical benefit to the subject.
Participants must have a histologically or cytologically confirmed advanced solid tumor of a non-breast origin, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective
Deemed a suitable candidate for radiation therapy by the treating radiation oncologist as documented in a standard pretreatment visit per standard practice at each participating institution
Prior standard or investigational anti-cancer therapy, as specified below:
Histologically confirmed advanced solid tumors with no clear curative treatment options available after at least 1 prior systemic anticancer therapy.
standard of care androgen deprivation treatment
Part 1: any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
Participants must have received, and then progressed, relapsed, or been intolerant to, all standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists
Expansion cohort(s): Progression during or following at least 1, and up to 5, previous systemic therapies, consistent with the standard of care for the specific tumor type.
Has failed (refractory) or relapsed after no more than 2 prior regimens, and for whom for whom no other standard therapy options are available.
no standard therapeutic options available (to be supplemented)
Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option
Participants who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible participants should not have available therapies that will convey clinical benefit and/or are not suitable options per the treating physician's judgment
Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
Standard treatment is not available
Dose escalation cohorts of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor, who have progressed despite standard therapy, or for whom no standard therapy is available.
Dose expansion groups of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with at least one measurable lesion as determined by RECIST version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor (for FAZ053 single agent no treatment with an anti-PD-L1 inhibitor is permitted), who have progressed despite standard therapy, or for whom no standard therapy is available and fit into one of the following groups:
Malignancies for which there is no standard therapy, or previously treated locally advanced, refractory/relapsed or metastatic disease for which local curative surgery, curable radiotherapy, or satisfactory systemic anticancer therapy is no longer available
Participants must have a pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
Have histologically or cytologically confirmed diagnosis of advanced solid tumor cancer (excluding lymphomas) for which there is no further standard therapy or when standard therapy is contraindicated. Patients with HGG must have shown unequivocal evidence for recurrence or progression by MRI scan or must have histologically proven tumor recurrence.
Patients must have histological diagnosis of melanoma or non-small cell lung cancer (biopsy will be done per standard of care, if needed to prove metastatic melanoma and/or NSCLC as well as for clinically relevant mutation analysis); additional biopsy will be per standard of care
All melanoma patients may be tested for BRAF as part of routine standard of care, but is not a requirement for the trial; all NSCLC patients may be tested for with EGFR and ALK as part of standard of care, but is not a requirement of the trial
A positive pregnancy test will exclude patients from the study in addition to excluding them from receiving standard therapy
Not pregnant per radiation oncology standard procedures
Phase 1a: histological or cytological confirmation of a solid, malignant tumor, excluding CNS tumors, that is refractory to standard therapies or for which no standard therapies exist.
Patients must have previously received and progressed on standard-of-care therapy(ies).
Patients with other immune checkpoint naïve histologically/ cytologically confirmed advanced solid tumor type that has received and progressed on standard-of-care therapy(ies).
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
The patient must have histologic or cytologic evidence of a malignant solid tumor and must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit.
All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
Inclusion Criteria:\n\n          -  Histologically confirmed solid malignancy that is metastatic or unresectable for which\n             standard curative or palliative measures do not exist or are no longer effective (Dose\n             Escalation phase only)\n\n          -  Measurable disease according to RECIST v 1.1\n\n          -  Eastern Cooperative Oncology Group (ECOG) score of 0 or 1\n\n          -  Normal organ and marrow function\n\n        Dose Expansion phase specific additional inclusion criteria:\n\n          -  Patients with metastatic colorectal cancer with no available therapy options that are\n             known to provide clinical benefit per institutional standard of care. (colorectal\n             cancer cohort only)\n\n          -  Patients must have a histologically confirmed epithelial ovarian cancer, primary\n             peritoneal cancer or fallopian tube solid tumor cancer that is locally advanced or\n             metastatic with no available therapy options that are known to provide clinical\n             benefit per institutional standard of care. (ovarian cancer cohort only)\n\n          -  Patients must have histologically or cytologically confirmed cervical squamous cell\n             carcinoma that is locally advanced or metastatic with no available therapy options\n             that are known to provide clinical benefit per institutional standard of care.\n             (cervical cancer cohort only)\n\n          -  Patients must have histologically or cytologically confirmed head and neck squamous\n             cell carcinoma that is locally advanced or metastatic with no available therapy\n             options that are known to provide clinical benefit per institutional standard of care.\n             (various solid tumors cohort: head and neck squamous cell carcinoma groups only).\n\n          -  Patients must have received prior therapy with an anti-PD-1 or anti-PD-L1 antibody, or\n             previously participated in Merck MK 3475 clinical trials. Patients must have\n             experienced documented, confirmed radiographic progression of disease by iRECIST, or\n             by RECIST v1.1 (various solid tumors cohort head and neck squamous cell carcinoma,\n             Check point inhibitor experienced group only).\n\n          -  Patients must have histologically or cytologically confirmed small cell lung carcinoma\n             that is locally advanced or metastatic with no available therapy options that are\n             known to provide clinical benefit per institutional standard of care. (various solid\n             tumors cohort, SCLC group only)\n\n          -  Patients must have histologically or cytologically confirmed cholangiocarcinoma that\n             is locally advanced or metastatic with no available therapy options that are known to\n             provide clinical benefit per institutional standard of care. (various solid tumors\n             cohort, cholangiocarcinoma group only)\n\n          -  Patients must have histologically or cytologically confirmed mesothelioma that is\n             locally advanced or metastatic with no available therapy options that are known to\n             provide clinical benefit per institutional standard of care. (various solid tumors\n             cohort, mesothelioma group only)\n\n          -  Patients must have histologically or cytologically confirmed carcinoma of the\n             esophagus including the gastroesophageal junction that is locally advanced or\n             metastatic with no available therapy options that are known to provide clinical\n             benefit per institutional standard of care. (various solid tumors cohort,\n             gastroesophageal carcinoma group only)\n\n        Exclusion Criteria:\n\n        Exclusion criteria apply to all phases and cohorts in the study unless otherwise stated\n\n          -  Prior monoclonal antibody, within 4 weeks prior to first dose of study drug.\n\n          -  Prior chemotherapy, targeted small molecule therapy or radiotherapy within 2 weeks\n             prior to first dose of study drug.\n\n          -  Patients who have received any other investigational agents within 4 weeks of first\n             dose of study drug.\n\n          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic\n             T-lymphocyte-associated antigen-4 (CTLA-4) antibody. (Not applicable for various solid\n             tumors cohort, head and neck squamous cell carcinoma check-point inhibitor experienced\n             group)\n\n          -  History of allergic reactions attributed to compounds of similar chemical or biologic\n             composition to birinapant or pembrolizumab or their constituents.\n\n          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic\n             congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia,\n             autoimmune disease or inflammatory diseases, or psychiatric illness/social situations\n             that would limit compliance with study requirements.\n\n          -  Evidence of active, non-infectious pneumonitis or a history of interstitial lung\n             disease.\n\n          -  Known history of Human Immunodeficiency Virus (HIV (HIV1/2 antibodies), or Active\n             Hepatitis B (HBsAg reactive. Active Hepatitis C (HCV-RNA qualitative).\n\n          -  Currently breast feeding, pregnant or planning to conceive or father Children from\n             screening through 120 Days after last dose of study drug.\n\n          -  Patients who have received anti-PD-L2, anti-CD137, or anti-Cytotoxic\n             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other\n             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)\n             (Various solid tumor cohort, head and neck squamous cell carcinoma check point\n             inhibitor experienced group only)
DOSE ESCALATION COHORT: Histologically or cytologically confirmed diagnosis of advanced extracranial solid tumor for which standard curative or palliative measures do not exist or are no longer effective
CMML that is refractory to, or progressed following treatment with a hypomethylating agent or other standard of care treatment
Subject has any evidence of metastatic disease (pre-operative staging will be undertake per urologic standard of care) as deemed by the Investigator
Progression on standard therapy, not a candidate for further chemotherapy or patient declines other options
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy
Must have received appropriate standard of care
recurrent/refractory disease after they received at least one prior standard treatment regimen
Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of non-critical location accessible to biopsy (with exception of non-small cell lung cancer [NSCLC] participants), and with confirmed progression at baseline that has progressed on, or participant is intolerant to, the standard of care therapy
Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded; for eligibility on this trial, allogeneic stem cell transplantation is not considered a standard curative option
Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
(Part 1 only) Have a histologically or cytologically confirmed diagnosis of advanced solid tumor that has relapsed or is refractory to standard curative or palliative therapy or has a contraindication to standard therapy.
Advanced stage solid tumors as documented by histological or cytological evidence, with no available approved therapies known to cure metastatic disease or extend survival, and who have received all standard therapy.
Patients with the TP53wt hematological tumors (AML, ALL, HR-MDS) who have failed prior therapies or who are considered inappropriate candidates for standard induction therapy.
Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed or for which standard therapies do not exist
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Patient must have an advanced (metastatic or recurrent) pathologically proven solid tumor which has not responded to standard therapy or which has progressed following standard therapy for advanced disease and/or for which no standard therapy is known to be effective; patients in expansion cohort A must have accessible tumor for biopsy
Patients must have disease that is no longer considered responsive to available conventional modalities or treatments (failed any known standard curative or effective therapy for that disease).
Progressive disease following at least one first line standard therapy.
Relapsed following or progressed through standard therapy
Have a disease for which no standard effective therapy exists (i.e., a therapy that demonstrates a significant increase in survival)
Disease that is refractory to or relapsed from either a hypomethylating agent (e.g. decitabine or azacitidine) or a standard AML-type intensive regimen
For the cohort 1, eligible patients must have a histologically, cytologically or radiographically proven metastatic or locally advanced solid tumor of any type, for which there is no curative standard therapy or standard therapy has failed
Non-GCB of origin by standard immunohistochemical classification
Subjects must have progressed on or after standard first-line systemic chemotherapy
Locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care; or for whom a clinical trial of an investigational agent is considered an acceptable treatment option
Patients for whom no standard curative therapy exists
Patients must have a diagnosis of a solid tumor malignancy and is refractory to standard therapies who have relapsed after standard therapy, or whose cancers have no standard therapy.
For the dose escalation phase: Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumor and have failed available standard of care (SoC) therapy and for whom no curative therapy is available or who are not eligible, intolerant to or refuse standard therapy.
Part A of the study will include patients that have histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
Previously untreated patients who decline standard therapy for their cancer are allowed to enroll
Histologically-proven, unresectable locally advanced or metastatic solid tumors of any histology that test positive for B7-H3 expression on tumor cells or vasculature for whom no approved therapy with demonstrated clinical benefit is available. For all tumor types, the requirement for previous systemic therapy may be waived if a patient was intolerant of or refused standard first-line therapy
Has relapsed from or is refractory to standard treatment or for which no standard treatment is available
Patients must have histologically confirmed melanoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
COHORT 3: ENDOMETRIAL CANCER: Patients must have histologically or cytologically confirmed persistent or recurrent advanced or metastatic invasive endometrial cancer (EC) for which standard curative measures do not exist or are no longer effective
Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
Patients for whom other curative or established standard-of-care therapeutic options with acceptable morbidity exist
Patient must have recurrent or advanced cancer (i.e., solid tumors) for whom standard therapy offers no curative potential.
Subjects must not have received any prior standard or investigational anti-tumor therapy other than surgery and must not intend to receive any standard or investigational anti-tumor therapy other than the study regimen
Prior use of any standard or investigational anti-tumor therapy other than surgery
Must have refused standard of care chemotherapy for metastatic disease
Patients must be considered candidates for prostatectomy as per standard of care
Surgically sub-total or unresectable tumors, i.e. in insula, including but not limited to the insula and received standard of care (SOC) radiation
Prior treatment with sipuleucel-T (on clinical trial or as part of standard of care)
Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after failing at least one course of community standard systemic treatment with chemotherapy (and endocrine therapy if appropriate)
AML that is refractory to or relapsed after standard induction therapy.
Subjects with histologically or cytologically proven advanced or metastatic solid malignancies for whom no effective standard therapy exists or has failed or subjects who are intolerant to established therapy known to provide clinical benefit for their condition (dose escalation cohorts; Part I).
All patients must be refractory to approved standard systemic therapy
Have had at least 1 prior line of standard therapy
For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy.
Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
Histologically confirmed advanced cancer or metastasis, which has not responded to standard therapy, producing intractable chronic pain in the target area.
Failure to respond to standard of care checkpoint blockade therapy or previously responding patients who progress on checkpoint blockade therapy
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part 1 (minimum of 1 prior line of AML-directed therapy)
Patients who have received and failed, or have been intolerant to, standard first line therapies known to confer clinical benefit; patients who refuse standard therapy would also be eligible, as long as their refusal is documented
Patients must have histologically confirmed HER2-positive breast cancer for which standard curative measures do not exist or are no longer effective; HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity
Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
Patients must have progressive tumor growth after having received established standard of care treatment for their disease
Patients with advanced cancer that is refractory to standard therapy, or that has either relapsed after standard therapy or has no standard therapy that increases survival by at least three months
Must have a histological diagnosis of epithelial adenocarcinoma of ovarian, tubal or peritoneal origin that is persistent or progressive following multiple rounds of prior standard of care and experimental therapy.
At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2)
Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor
Must be refractory or intolerant to standard lines of therapy
Meets standard of care to undergo embolization
Follow standard of care donor eligibility procedure, outlined in the standard operation procedure (SOP)
This study will include all patients clinically suspected or histologically confirmed solid or hematological malignancy who have undergone or will undergo genetic testing of their tumor; patients may have failed first-line or standard therapy for their disease (refractory) or have no options for curative therapies; rare cancers that are metastatic at diagnosis are by definition refractory and may be included in the first line setting, at the discretion of the principal investigators; rare cancers may not have standard of care therapies - a disease/tumor is considered rare if the incidence is < 6/100,000/year using the National Cancer Institute (NCI) RareCare tumor list, or if the disease is a molecular or biologically defined subset such that the annual incidence is < 20,000 in the United States
Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:\r\n* Failed to respond to standard therapy or\r\n* For whom no standard therapy is available or\r\n* Refuse to receive standard therapies
Completion of at least one standard of care IV chemotherapy course; hematologic recovery must be confirmed prior to study entry;
To commence first-line standard nab-paclitaxel and gemcitabine chemotherapy, or gemcitabine alone, (per standard of care according to the approved prescribing schedule), within 7 to 14 days post enrolment, with OncoSil™ implantation to occur during the fourth (4th) week of the first chemotherapy cycle
Being considered for trabectedin as standard of care
Patients must be planning to undergo standard radiation/chemotherapy
Planning to undergo additional treatment for the brain tumor other than standard of care
Patients may be enrolled in any line of standard treatment (without investigational agents); the start date of current treatment should be at least two 2 weeks or more prior to registration; (Note: patients will continue to receive the planned active treatment with chemotherapy or endocrine therapy [standard of care] and initiate denosumab at the recommended dose for this protocol)
Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after failing at least one course of community standard systemic treatment with chemotherapy (and endocrine therapy if appropriate)
Subjects with advanced or metastatic solid tumors that are refractory to standard therapies known to provide clinical benefit. Subjects with hematologic malignancy including lymphoma/myeloma will not be enrolled on this study.
Patients with advanced solid tumors that are refractory to approved therapy and have had at least one line of systemic treatment with chemotherapy, immunotherapy, hormonal therapy, or other standard treatments for metastatic disease
Patients must have disease that has relapsed after or is refractory to at least 2 lines of standard therapy; the remaining standard treatment options are unlikely to be effective in the opinion of the treating physician, or patient is felt to be ineligible for such therapies or the patient refuses such therapies; patients who have undergone autologous stem cell transplant are eligible as long as they meet all other criteria
Any candidate eligible for standard of care Y90 radioembolization for treatment of their primary or metastatic liver tumors
Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy
During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC. Prior use of cisplatin (or carboplatin) is permitted.
Arm A dose escalation: patients with histologically or cytologically proven advanced solid tumors for which standard treatments are not available, or for whom the current dose level of cisplatin in combination with pemetrexed is appropriate; =< 2 prior cytotoxic chemotherapy regimen
Patients must have a diagnosis of advanced or metastatic malignancy that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients must have histologically confirmed neuroendocrine tumor (grades 1-3) that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective
Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy or not amendable to a curative treatment
Subjects must have a histologically or cytologically proven advanced solid tumor malignancy for which palliative radiation is recommended. In solid tumors where pembrolizumab has been approved for use, patients may receive pembrolizumab as indicated, in the context of this protocol; in solid tumors where pembrolizumab has not been approved for use, the following criteria apply:\r\n* Patients must be resistant to at least 1 prior conventional chemotherapy regimen or other standard of care regimen,\r\n* Patient must have no remaining conventional treatment options proven to provide long-term disease control, and\r\n* Patient has declined other conventional treatment options\r\nPalliative radiation therapy may be recommended for primary tumor and/or any metastatic site that is accessible to biopsy
All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
Must be eligible for treatment with nivolumab as standard of care
Patients with advanced or metastatic cancer that is refractory to standard therapy or that has relapsed after standard therapy or has no standard therapy that increases survival by at least three months
Recurrent or refractory disease for which no further effective standard treatment is available
Diagnosis with a histologically confirmed non-small cell lung cancer (NSCLC) or other refractory solid tumor that is metastatic or unresectable for which there is no standard curative or palliative treatment option available and where targeting EGFR may be appropriate
If an approved first-line standard therapy for the patient’s tumor is available, subjects must have failed, be intolerant to, be ineligible for, or have refused that treatment; enrollment of patients for whom no standard therapy exists or who decline standard therapy should be discussed with the principal investigator prior to enrollment; patients must have progressive disease on study entry
All patients must have received prior first line standard therapy or declined standard therapy
Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred
Patients for whom no standard curable therapy exists
Diagnosis of one of the following: 1. Part 1: Histologically- or cytological-confirmed diagnosis of non-resectable or metastatic solid malignancy. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected to achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy, OR have a disease for which no generally-accepted standard-of-care exists. 2. Part 2: Histologically- or cytologically-confirmed diagnosis of metastatic or non-resectable triple-negative breast cancer (TNBC) (estrogen receptor [ER]-/ progesterone receptor [PR]-/Human Epidermal Growth Factor Receptor 2 [Her2]-, as defined by local laboratory standards); metastatic or non-resectable transitional cell carcinoma of the bladder, ureter, or renal pelvis; recurrent GBM; or non-Hodgkin's lymphoma. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy.
PHASE I: Patients must have advanced solid tumor that is resistant or refractory to standard therapy
Recurrence or progression of disease (confirmed by MRI and measurable by RANO criteria) following receipt of standard of care therapy, which includes maximum safe surgical resection, standard adjuvant radiation/temozolomide treatment. Participants must have completed at least 21 days of temozolomide treatment in combination with radiation therapy to be considered to have received standard of care therapy.
Failure to respond to standard therapy, or for whom standard or curative therapy does not exist, or is not tolerable. a. Subjects enrolled in the Expanded Cohort should have no more than 3 prior systemic regimens with confirmed disease progression. If the subject is refractory or has disease progression within 6 months of the adjuvant treatment, then the previous treatment should be considered as the line of treatment rather than an adjuvant therapy.
Dose Escalation Cohort: Patients must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists
Subjects with solid tumor types other than TNBC may also be enrolled after discussion with the sponsor; these subjects must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists
Be within 6 months (+/-1 week) between last dose of an immunotherapy agent and study enrollment\r\n* Patients may continue with maintenance immunotherapy as part of standard of care therapy while receiving radiation
Has a histologically or cytologically confirmed diagnosis of a solid tumor malignancy (except for any excluded malignancies listed in the Exclusion Criteria) that is not responsive to standard therapy(ies) or for which there is no approved therapy.
The patient must be eligible for standard of care treatment with gemcitabine +nab-paclitaxel.
Planning to undergo standard preoperative radiotherapy
Patients must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist
Histologically or cytologically confirmed advanced or metastatic solid tumor or l lymphoma, that is refractory to standard therapy, relapsed after standard therapy, or for which no standard therapy available that is expected to improve survival by at least three months
Subjects must be planning to start standard of care radiation therapy and chemotherapy
Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy
Patients must have histologically (or cytologically)-confirmed diagnosis of solid tumor, refractory after standard therapy for the disease or for which conventional systemic therapy is not reliably effective or no effective therapy is available.
Failed any previous front line standard of care therapy that is currently used for the patient’s initial diagnosis
Patients who are refusing first line standard of care chemotherapy
Solid tumor specific:\r\n* Patients must have a histologically/cytologically confirmed primary solid tumor\r\n* Radiographic or clinical evidence of advanced/metastatic disease that is resistant to standard therapy or for which no standard therapy is available; lesions may be measurable or non-measurable
Agree to attend study visits outside of standard of care visits, if needed
Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
Histologically or cytologically confirmed solid tumors or lymphomas that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Histologically or cytologically documented, locally advanced or metastatic solid malignancy that has progressed on available standard systemic therapy, and for whom no effective therapy or standard of care exists.
Patients currently receiving any other standard or investigational therapy for the treatment of AML
EGFR wt as per patient standard of care by a validated test
AND ALK-negative rearrangement as part of the patient standard of care by a validated test
Relapsed disease after standard chemotherapy
Cancer treatment other than radiation therapy, including investigational or standard of care, within 30 days prior to treatment with REGN2810
Patients for whom there is no further standard therapy available at the time of enrollment (Part A)
Have refused standard therapy
Progressed, or been intolerant to, at least one standard treatment regimen, except for subjects in 1st line cohorts.
PHASE I COMPONENT: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist; patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation
PHASE I: Patients with clear cell RCC must have either declined, be ineligible to receive, have progressed on, or be intolerant to high dose interleukin (IL)-2 , or standard first and second line VEGF, or mechanistic target of rapamycin (mTOR) targeted agents; as there is no standard therapy for metastatic non-clear cell RCC, no prior therapy is required
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients must have histologically or cytologically confirmed advanced solid tumor that is refractory to standard treatment or for which no standard treatment exists
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Recurrent, refractory or relapsed advanced stage melanoma defined as progression of disease through standard therapy or patient choice to not receive standard therapy; for those that received standard systemic therapy, treatment agents may have included (but are not limited to) ipilimumab or vemurafenib (for those patients that are BRAF v600e positive)
Patients with histologically confirmed, advanced or metastatic cancer for which standard curative or palliative measures do not exist or are no longer effective
Failure to respond to or refractory to approved/standard therapy; or for whom standard therapy does not exist, or is not tolerable; or for whom approved/standard therapy is not considered to be sufficient or appropriate by the Investigator.
Advanced solid tumor that has progressed during or after treatment with approved therapies or for which there is no standard effective therapy available\r\n* Note: patients with solid tumors for which regorafenib would be considered a standard treatment are eligible as long as regorafenib has not been previously administered
Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options. (Note: Osteosarcoma participants must be in first or subsequent relapse [greater than or equal to first relapse]). Only the osteosarcoma participants enrolled to Cohorts 3A and 3B must be deemed candidates for ifosfamide and etoposide chemotherapy).
Anticoagulants < 7 days prior to Day 1. Aspirin is permitted in Phase 1b per standard of care with lenalidomide-based therapy.
Patients with refractory or recurrent solid tumors for which there is no standard therapy are eligible; patients must have had histologic verification of malignancy at original diagnosis or at the time of relapse
Patients must have had a previous histological verification of a solid tumor at the original diagnosis and/or recurrence including brain tumors; for patients with brain stem gliomas and optic pathway tumors, the requirement for histological evaluation may be waived; the patient’s disease must be considered refractory to conventional/standard therapy, or a disease for which no conventional therapy exists and is progressive
PROCUREMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
TREATMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
Patients with a recurrent/metastatic or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists or is too toxic
Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that has failed or become intolerant to standard therapy
Completed all standard of care therapy (surgery + radiation as clinically necessary) prior to vaccination
Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment
Patient is receiving concomitant standard and/or investigational anticancer therapy; local palliative radiotherapy is permissible upon discussion with the principal investigator
Documented progression of disease according to RECIST v1.1 following primary standard of care (e.g. erlotinib, gefitinib) Group 2 patients:
Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
Candidate for known standard therapy for the patient’s disease that is potentially curative
Patients with an advanced solid tumor that is refractory to standard treatment, or for which no standard therapy is available, or the subject refuses standard therapy
Have failed, or could not tolerate, other standard of care therapies
Failed at least one standard chemotherapeutic treatment for NSCLC
Patients must have pathologically-confirmed solid tumors, refractory after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available.
Patients with advanced or metastatic cancer that is refractory to standard therapy or relapsed after standard therapy; patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients who have completed standard of care and recovered with mild to no residual toxicity from recent therapy
Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective
For initial VSTs and subsequent infusions: patients will be eligible following any type of allogeneic transplant if they have CMV, adenovirus, EBV, BK virus and/or HHV6 infection/disease persistent or recurrent despite 14 days of standard therapy OR after failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy; patients with persistent human polymavirus type II (JC) virus infection will be eligible as well
Patients must have histologically- or cytologically-confirmed diagnosis of KRAS or NRAS mutation-positive malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective; patients must have activating mutations affecting codons 12, 13, 61, or 146 as determined in a Clinical Laboratory Improvement Amendments (CLIA)-certified lab to be eligible for this study
If prior standard-of-care pre-treatment biopsy is inadequate for analysis by immunohistochemistry, and the patient is unwilling to undergo an additional biopsy procedure
Have histologic or cytological proof of advanced cancer that has progressed and for which there is no further standard anticancer therapy available in the opinion of the investigator.
Planned stereotactic biopsy as standard of care (i.e., for confirmation of disease progression)
Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any phase of standard therapy (any new lesion or an increase in size > 25% of a pre-existing lesion); patients may enter this study with or without re-induction therapy for recurrent tumor
Relapsed/refractory to at least one prior standard systemic treatment regimen, but no more than 4.
Patients with GI disorders who have failed standard therapy
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response of at least 10% or improves survival by at least three months; in addition, patients with disease that are “benign” by pathology, but relentlessly progressive, leading to disability, pain, and premature death in the majority of cases (including, but not limited to lymphangioleiomyomatosis [LAM], type 2 neurofibromatosis [NF], Erdheim Chester disease, and Castleman’s disease) may also be considered for enrollment
Patients with advanced or metastatic cancers and BRAF mutations that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months; patients with BRAF mutation in cell free deoxyribonucleic acid (DNA) (tested in Clinical Laboratory Improvement Amendments [CLIA] lab) are also eligible
Patients with advanced or metastatic cancer that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients aged < 60 years who are unsuitable for standard induction therapy may be eligible after discussion with principal investigator (PI)
Patients must have either (1) refractory or relapsed high-risk NB (including v-myc myelocytomatosis viral related oncogene [MYCN]-amplified stage 3/4/4S and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies\r\n* For NB, standard therapy generally includes 5-8 cycles of high dose induction chemotherapy followed by resection of gross residual tumor, then usually myeloablative chemotherapy with peripheral blood stem cell rescue and radiation therapy to the primary site; there are also salvage chemotherapy regimens for residual disease after standard induction therapy or for relapsed NB; some examples of these chemotherapy combinations are: high-dose cyclophosphamide, topotecan and vincristine; high-dose cyclophosphamide, irinotecan and vincristine; irinotecan and temozolomide; or ifosfamide, carboplatin and etoposide
Patients must have failed standard therapy and at the time of study entry have recurrent, progressive or refractory disease with no known curative options
Evidence that the tumor MGMT promoter is unmethylated by standard of care assays
Must not be a candidate for potentially curative therapy or standard-of-care approved therapy
Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
During the Dose Escalation Phase: only adult patients with active disease failing standard therapy
Subjects must have primary or metastatic liver malignancies for which are surgically unresectable, and exhausted all standard therapeutic options to be eligible for this study
Histologically and/or cytologically confirmed malignant solid tumor that is refractory to standard therapies, or for which no standard therapies exist; disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* For the non-small cell lung cancer (NSCLC) expanded cohort only: only histologically proven adenocarcinoma that is refractory to standard therapies
Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study
Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy
Must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy
no standard therapy options
Unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
Phase I: Patients must have histologic verification of a solid tumor or lymphoma malignancy at diagnosis for which there is no standard curative anti-cancer treatment or treatment is no longer effective and must have received ? 1 prior line of therapy.
Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (example, intolerance).
Progressive disease after failure of or intolerant to all available standard systemic treatments that have shown a documented benefit in overall survival for their respective tumor type.
Patients who refuse standard therapy are excluded from the study
Dose escalation: Patients with accessible tumors and with measurable disease as determined by RECIST 1.1 who have received at least one but no more than three prior lines of treatment for their disease and progressed despite standard treatment or are intolerant of standard treatment, or for whom no standard treatment exists
Dose expansion: Patients with advanced/metastatic solid tumors: head and neck squamous cell carcinoma (HNSCC), melanoma, accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients must have measurable disease as determined by RECIST 1.1, and have progressed despite standard treatment or are intolerant to standard treatment, or for whom no standard treatment exists and have received at least one but no more than three prior lines of treatment for their disease.
Mismatch repair deficiency as identified by immunohistochemistry or other institutional standard, or Epstein-Barr virus positivity as determined by in situ hybridization or other institutional standard
Patients must have metastatic disease that is either refractory to standard therapy or for which no effective standard therapy that confers clinical benefit is available
Patients with confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy; they could not tolerate standard therapy; or such measures are not acceptable to the subject.
Has disease that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
Have a histologically confirmed diagnosis of an advanced and/or metastatic solid tumor that is relapsed and/or refractory to standard therapy, as defined as progression on at least one prior line of therapy in the relapsed/metastatic setting and no existing options are felt to provide clinical benefit.
Patient with documented pathological evidence of a cancer from which has developed advanced unresectable solid tumors that are, in the opinion of their treating physician, refractory to standard therapy or for which no standard therapy is available
Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists.
Patients without confirmed progressive and/or refractory SM using standard RECIST criteria, or those with confirmed progressive and/or refractory SM using standard RECIST criteria.
Has histologically or cytologically confirmed advanced, unresectable metastatic solid tumor(s) for which the patients have no available therapy likely to provide clinical benefit, or for which paclitaxel is considered a standard of care.
Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed
Patients must be refractory or intolerant to at least 1 prior standard systemic therapy, if a candidate for systemic therapy
Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy
Histologically or cytologically confirmed malignancy or lymphoproliferative disorder known to over express CK2 which has failed standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy) or for which effective therapy is not available, including the following types: (examples)
Completed standard therapy ( at least 3 months of chemotherapy ± radiotherapy )
Within 120 days of completion of standard therapy (surgery, chemotherapy ± radiotherapy)
Must not be a candidate for potentially curative therapy or standard-of-care approved therapy.
Patients must have disease that is recurrent or refractory to standard therapy; patients must have failed front-line therapy and declined or are not candidates for autologous stem cell transplant (ASCT) or have failed prior ASCT
Histologically or cytologically confirmed diagnosis of advanced cancer in patients with solid tumors that are refractory to standard treatment, or for whom no effective therapy exists.
Patient has a desire to preserve organ, understanding the risks of delaying standard of care
Must have received or been intolerant to standard therapy.
For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors.
For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective.
Dose escalation cohort: histologically or cytologically confirmed diagnosis of a solid tumor that can be treated with either pembrolizumab or nivolumab as part of standard of care or whom no standard of therapy exists except pembrolizumab or nivolumab
Patients with planned standard of care ASCT using melphalan 200 mg/m^2
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Subject’s current disease state must be one for which there is no known curative therapy, or in the case of a new diagnosis there must be ? 15% chance of cure if given standard-of-care chemotherapy (prognosis to be determined at the discretion of the treating physician)
For the expansion cohort of non-small cell lung cancer (NSCLC) patients previously treated with and having progressed on immunotherapy patients must have no standard of care option available or have contraindications to such treatment (including those who decline such treatment)
Eligible for checkpoint inhibitor immunotherapy (pembrolizumab) per standard of care
Patient has advanced or metastatic breast cancer that is refractory to at least one standard therapy or that has relapsed after standard therapy or that has no standard systemic therapy that increases survival by at least 3 months.
Solid tumor malignancy for which no standard of care therapy is available which has a proven overall survival benefit
Treatment with bisphosphonates or denosumab is allowed and recommended per the standard of care
For Dose Escalation Cohort: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patient must have non-resectable disease that has progressed following standard therapy or has not adequately responded to standard therapy, or the patient must be intolerant to or have declined available standard therapies, or there must be no accepted standard therapy for their disease.
For the dose escalation part: Patients with selected, relapsed solid tumors who have failed available standard therapy or who are not candidates for standard therapy.
For the expansion part: Patients with relapsed, advanced and/or metastatic solid tumors who are not candidates for standard therapy
Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be intolerant of, have relapsed following, or have refused all standard life-prolonging therapies
For stratum A, patients must have local recurrent disease (defined as negative spine magnetic resonance imaging [MRI] and negative cytology within 21 days prior to study registration) and undergo resection of local recurrence as part of their standard of care; children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy
For the dose escalation cohort, patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
One of the following:\r\n* Age >= 60 years\r\n* Age < 60 years but unsuitable for standard chemotherapy because of a cardiac ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine clearance >= 30 and < 60 mL/min, or refused standard chemotherapy despite efforts to convince them otherwise
< 60 years who are considered candidates for standard chemotherapy
Phase 1: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists, or infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists, or patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. The Phase I dose escalation cohorts are closed to enrollment. In addition to the above stated Inclusion Criteria, patients eligible for enrollment into this cohort must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS.
In Cohorts A3 and A4 only, participants with AML eligible for standard intensive induction therapy with an anthracycline and cytarabine
Planned standard treatment with pembrolizumab
Patients must have relapsed after or be refractory to effective standard therapies; for NF1 PN there is no standard medical therapy, and therefore no requirement for prior therapy; there are no limits on number of prior therapeutic regimens
Standard, curative or palliative measures do not exist or are no longer effective
TUMOR BIOPSY SEQUENCING: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival
TREATMENT: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy or for which no standard therapy exists that has been shown to prolong survival
ARM B: Histologically or cytologically confirmed solid tumor with subcutaneous/cutaneous lesions that is refractory (RECIST or with unequivocal clinical progression of disease) to or intolerant to standard therapy
Patients must have histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (i.e., lung, ovarian, breast, melanoma, head and neck, endometrial, urothelial, testicular, esophageal, carcinoma of unknown primary); for indications not listed, eligibility based on disease must be verified by the principal investigator before they are considered
PHASE I: Adult patients with histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative measures or other therapy definitely capable of extending life expectancy does not exist
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
DOSE ESCALATION COHORT: Subjects with advanced and unresectable solid tumor who progressed on at least one line of systemic therapy, and no approved therapy or standard therapy with demonstrated clinical benefit exists; and all subjects with T790M mutation positive NSCLC have progressed on osimertinib\r\n* Note: disease measurability is not required for dose escalation
Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins
Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:\r\n* Non-M3 AML refractory to standard primary induction therapy \r\n* Non-M3 AML relapsed after (i) any standard induction therapy (ii) any number of standard or experimental salvage therapies\r\n* Newly diagnosed non-M3 AML not eligible for intensive induction chemotherapy
Subjects who are suitable for and willing to receive standard intensive induction therapy
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
Cohort 1 (dose escalation): histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes
Known standard therapy for the patient’s disease that is potentially curative
Ability to tolerate intensive therapy with vosaroxin 90 mg/m^2 and standard dose of cytarabine as per investigator discretion
Patients must have pathologically confirmed diagnosis of a solid tumor cancer for which there is no known standard therapy capable of extending life expectancy
Histologically or cytologically proven diagnosis of hematologic malignancies for whom all standard therapy options have failed
Malignancy that is incurable and for which standard (FDA approved or established standard clinical practice) curative, or palliative measures do not exist or are no longer effective
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy; EXCEPTION: For platinum-resistant ovarian cancer, because nab-paclitaxel has known benefit, patients who may benefit from standard single agent chemotherapy are also eligible to participate
Subjects must be within 4 to 6 weeks of standard of care treatment for their particular stage of disease
Subjects must not be more than 6 weeks from standard of care treatment for their particular stage of disease
COHORT I (DOSE ESCALATION): histologic proof of cancer that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
COHORT I (DOSE ESCALATION): known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy
Subjects having histologically and/or cytologically confirmed non-haematological\n             malignancy that is metastatic or unresectable and for which standard curative or\n             palliative treatment does not exist or is no longer effective
Participants must have histologically or cytologically confirmed diagnosis of either:\r\n* Ovarian, fallopian tube, or primary peritoneal cancer of high grade serous histology which has recurred despite standard therapy or\r\n* Triple-negative breast cancer which has recurred despite standard therapy
Advanced or metastatic cancer for which no standard therapy exists or that has\n             progressed despite standard therapy
STANDARD RISK PATIENTS:
Both patients who will and will not receive standard of care concomitant mitomycin C are eligible to enroll in this study
Advanced (unresectable) solid tumors: patients must have failed or been intolerant to at least one line of standard therapy or refuse standard treatment
Patients must have advanced/metastatic solid malignancy or lymphoma for which no standard treatment option exists that will confer clinical benefit
DOSE ESCALATION PHASE: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists
Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:\r\n* Failed to respond to standard therapy or\r\n* For whom no standard therapy is available or\r\n* Refuse to receive standard therapies\r\n** The study is intended to enroll patients with melanoma, renal cell, and pancreatic cancer; patients with other types of solid tumors will require approval by the principal investigator
Patients must have a histologically/cytologically confirmed diagnosis of recurrent glioblastoma or an advanced solid tumor in which bevacizumab has shown benefit in specific disease population and for which standard or curative measures do not exist or are no longer effective
Any standard therapy for leukemia within 14 days before enrollment (except for hydrea)
Must have prior biopsy at any time point diagnostic for confirmed MF stage IIA-IVA, and must have failed at least one standard therapy (topical or systemic); this is mandatory
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
Patients must have adequate TIL available as described in the Moffitt Cell Therapy Core standard operating procedures (SOP)
Subjects with advanced refractory cancer for which standard curative or palliative\n             measures do not exist or are no longer effective. There is no limitation on the\n             number or types of prior therapy.
Histologic proof of cancer which is now not amenable to alternative curative or clearly superior standard treatment options
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy
Patients with histologically or cytologically proven advanced solid cancer and have undergone treatment with at least one regimen of standard therapy, either cytotoxic chemotherapy, a molecularly targeted agent, or immunotherapy, or have a form of cancer for which no standard therapy exists; patients with prostate cancer may continue on androgen-deprivation therapy if they are currently receiving it
Histologic or cytologic confirmation of a solid malignancy with established intolerance or refractoriness to standard therapies
Patients must have histologically proven solid tumors (Phase I) with biopsiable tumor (expansion cohort) refractory to standard therapy or for whom no standard therapy exists or who decline standard therapy
Eligibility for brachytherapy is determined per clinical standard of care
Patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease
Potential patients referred for the study may not be eligible for the experimental protocol therapy due to reasons such as uncertainty about donor HLA typing or need to control malignant disease, infection, or metabolic abnormality such as hypercalcemia on an emergent basis; should a referred patient present to us in such a scenario, the patient will be referred back to their primary hematologist-oncologist for treatment; however, if referral back to the referring physician is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease or complicating conditions (infection, metabolic problems) under the current study; in other cases, a patient may have reasonable control of malignancy but does not meet the CD4 cell cut-off of 100 cells per microliter required for cohort 3 therapy (or, absolute lymphocyte count [ALC] value of < 300); in such cases, standard care chemotherapy regimens may be administered for the specific goal of reducing the CD4 count (that is, immune depleting regimens such as the pentostatin plus cyclophosphamide combination, administered similar to the manner that we have developed on protocol 08-C-0088); if it becomes apparent that the patient will not be able to proceed to experimental therapy, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol; because such standard care therapy is not experimental, it is not necessary to complete the eligibility criteria prior to receiving such standard care; however, prior to initiation of the experimental therapy, the patient must meet each of the eligibility criteria detailed above; attempts will be made to standardize such pre-transplant chemotherapy (by administration of EPOCH-FR chemotherapy); however, other regimens using approved agents will be allowed if such regimens are thought to be in the best interest of the patient
Has relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion
Advanced metastatic or unresectable malignancy that is refractory to standard therapy and/or existing therapies are not likely to achieve clinical benefit, and/or the patient declines to receive standard treatment such as chemotherapy.
Plan to administer any other systemic antitumor including endocrine therapy except for following standard of care treatment:\r\n* Trastuzumab at standard dosing human epidermal growth factor receptor 2 (HER2) positive tumors\r\n* Denosumab or bisphosphonates to treat metastatic bone disease
Relapsed or refractory disease after standard therapy including brentuximab vedotin (Adcetris®).
Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment
During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
Acute Minnesota Standard Risk GVHD requiring systemic immune suppressive therapy.
Patient must have histologically or cytologically confirmed solid tumor, including glioma, with documented IDH1 and/or IDH2 gene-mutation. Patients in the dose escalation phase must have disease that has recurred or progressed following standard therapy and/or therapy with an inhibitor of mutant IDH1 and/or IDH2, or that has not responded to this therapy. Patients in the expansion phase may have previously untreated disease
Antiviral therapy per local standard of care if active hepatitis B (HBV) infection.
Subjects who are not eligible for standard chemotherapy
Histologic documentation of locally advanced, recurrent or metastatic incurable solid malignancy that has progressed after all available standard therapy or for which standard therapy has proven to be ineffective or intolerable, or is considered inappropriate
Histologically or cytologically proven metastatic or locally advanced tumors for which no standard therapy exists, or where standard therapy has failed, or in patients otherwise ineligible for standard therapy, or for an indication that anti-programmed cell death protein 1 (PD-1) therapy has been shown to be effective in studies in HIV-uninfected participants; disease-specific criteria will be applied for certain common cancers and cancers strongly associated with HIV; however, enrollment will not be confined to these tumors
Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
Subjects must have received and have progressed, or are refractory to standard regimens
Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab; if a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy
Contraindications to the planned second line standard-of-care chemotherapy regimen
Part 1: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject refusal or intolerance is also allowable).
Part 2: *Note: Subjects must have failed available therapies that are known to confer clinical benefit as indicated below, unless they are ineligible, intolerant, or refused standard treatment.
Subjects who have progressed or have been intolerant to any standard treatment regimen or refused standard treatment, or for which adequate standard therapy does not exist.
Subject has HBV DNA viral load undetectable or < 100 IU/mL at screening. If subject has detectable HBsAg, HBeAg, or HBV DNA (indicating ongoing viral replication of hepatitis B, he/she must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. If not on antiviral therapy at screening, then the subject must initiate treatment per regional standard of care guidelines prior to C1D1 and must be willing to continue antiviral therapy while on study treatment.
Histologic documentation of locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy is ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is recognized standard of care
Histologically or cytologically confirmed diagnosis of advanced solid tumors that have relapsed from or are refractory to standard treatment or for which no standard treatment is available
Diagnosis - Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available.
Confirmed diagnosis of advanced malignancies that may be controlled with p70S6K or Akt inhibition based on already identified molecular alteration known to affect the PAM pathway, such as:: such as: such as: phosphate and tensin homolog (PTEN), phosphoinositide 3-Kinase catalytic subunit alpha isoform (PIK3CA), protein kinase B 1 (Akt 1), Akt 3, mammalian target of rapamycin (mTOR), tumor sclerosis complex 1 (TSC1), tumor sclerosis complex 2 (TSC2), in subjects who have received at least all treatment options considered to be standard therapy, unless some available treatment are not acceptable to the subject. For the dose escalation portion of the trial, subjects must have received the standard therapy unless intolerant or contraindicated.
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.
Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment.
Patients who are candidates (eligible and willing) for standard and/or potentially curative treatments are not eligible
Subjects who are eligible for further standard of care endocrine treatment.
Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer.
Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
Patients with histologically/cytologically confirmed advanced solid tumors with FGFR1 or FGFR2 amplification or FGFR3 mutation, for which no further effective standard anticancer treatment exists
Patients must have histologically or cytologically confirmed diagnosis of malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or for whom CPT-11 treatment would be a viable therapy regimen; patients with solid hematologic malignancies (Hodgkin’s and non-Hodgkin’s lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of treatment
Patients enrolled on the dose escalation for intermittent ABT-888 portion of the study must histologically or cytologically confirmed diagnosis of malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or for whom CPT-11 treatment would be a viable therapy regimen; patients with solid hematologic malignancies (Hodgkin’s and non-Hodgkin’s lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of treatment
Histologic proof of cancer which is now not amenable to curative standard treatment options
Patient must have received at least 1 prior standard therapy for their disease
Any evidence of metastatic disease; pre-operative staging will be undertaken per urologic standard of care
Prior standard or investigational anti-cancer therapy as specified in protocol
A histologically or cytologically confirmed solid tumor that is metastatic, unresectable, or recurrent and for which standard therapies do not exist or are no longer effective a. Patients must not be considered eligible for a potentially curative resection
Subjects must have previously completed standard radiation therapy and been exposed to temozolomide. Patients must be in first or second relapse.
Subjects must have a histologically confirmed malignancy that is metastatic or unresectable for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit or they must be ineligible to receive such therapy and/or have declined all such therapy. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
Metastatic or inoperable solid tumors* (except gastrointestinal tumors or tumors that originated or metastasized to the liver) for which no standard treatment exists, or have progressed or recurred following prior therapy.
Patients in expansion cohort A will have a biopsy (which is standard of care) at the time of progression that shows evidence of MET positivity
Eligible to receive standard-of-care sorafenib
Subjects who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no standard anticancer therapy exists. Must have disease that is objectively measurable
Patients must have a histologically confirmed non-hematological malignancy established by biopsy or resection; patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible
For Phase 1, subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject intolerance is also allowable).
Part A only: Histologically or cytologically confirmed metastatic and/or advanced solid tumors with documented progressive disease for whom no further standard therapy is indicated.
Group 2: BRAFV600 positive metastatic colorectal carcinoma (CRC), or advanced non-small cell lung carcinoma (NSCLC) after failure of at least two lines of prior standard therapy or for whom no further standard therapy is indicated.
Group 3: Advanced solid tumors with PI3K pathway alterations (PIK3CA mutation or PTEN loss) after failure of at least one line of prior standard therapy or for whom no further standard therapy is indicated. Prior treatment may not include inhibitors of the PI3K pathway.
Subjects must have no standard therapy available, or have actively refused standard therapy
are, in the judgment of the investigator, appropriate candidates for experimental therapy after available standard therapies have failed to provide clinical benefit
Histologically or cytologically confirmed advanced solid tumors (excluding HCC) that have progressed following standard therapy, or for which no standard therapy exists (including surgery or radiation therapy) or participants with RR-DTC.
Refractory to or intolerant of standard therapy
Ovarian cancer defined as a histologically confirmed diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer refractory to standard therapies of for which no standard therapy exists. Confirmed BRCA1 or BRCA2 mutation from a prior test. Patient progressed while receiving and/or following treatment with a PARP-inhibitor for advanced disease (recurrent or metastatic.
Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
Standard treatment interrupted, except if anti-HER2 therapy
Use of any other standard or experimental therapy within 14 days of starting study therapy
Subjects must have a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy is available.
Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy
Eligible to receive standard of care chemotherapy and/or surgery based upon standard practices or institutional guidelines
Prior treatment with standard first line therapy in the metastatic setting
Subjects >= 60 years of age with AML who are not candidates for or have refused standard chemotherapy.
Failure of at least one prior standard of care chemotherapy for advanced stage disease
Has stable, or no evidence of, extracranial disease and not receiving systemic therapy for extracranial disease; Note: patients with stable disease must have already received standard therapy or are intolerant to standard therapy
Patients must have a diagnosis with solid tumors and lymphomas, either refractory to standard therapy or for which no effective standard therapy that conveys clinical benefit
Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy. Patients must have measurable disease
Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
In countries where continuous anti-HER2 therapy is considered standard of care for HER-2 positive metastatic disease, HER-2 positive subjects are not eligible.
Subject has histologic or cytologic confirmation of advanced solid tumors that is refractory to standard therapy or for which no standard therapy is available
Diagnosis - CD30+ HL or CD30+ NHL:\r\n* During the dose escalation phase: only adult patients with active disease failing standard therapy\r\n* After dose escalation: any patient (children or adults) newly diagnosed, unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and autologous stem cell transplantation
Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy
Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
Patients with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen
Histological or cytological confirmation of advanced unresectable solid tumors, including those subjects who have progressed on standard anticancer therapy and for whom no further therapy that confers clinical benefit is available.
Patients enrolled in the dose escalation stages must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit or if such therapy has been refused by the patient. Documentation of the reason must be provided for patients who have not received a standard therapy likely to result in clinical benefit.
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to SOC, or for whom no standard therapy exists. Patients must fit into one of the following groups: • CRC •NSCLC • TNBC• RCC
Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant)
Patients undergoing Surefire DEB-TACE procedure as clinically determined to be part of their standard of care treatment plan
Participants must have relapsed disease despite standard therapy
At least one tumor for which palliative RT is considered appropriate standard therapy
Known standard therapy for the patient’s disease that is potentially curative
Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects either refuse standard curative or palliative therapy, are not candidates for standard curative or palliative therapy, have a disease for which no non-investigational therapy exists, OR have progressed on prior therapy (up to three lines of prior cytotoxic agents are permitted).
Patients must have histologically confirmed solid tumor malignancy (excluding primary brain tumor) that is metastatic or unresectable and have failed standard therapies; patients are also eligible patients declined (or if their physicians determined them unsuitable for) standard therapy options.
Patients who declined standard therapies or whose physicians determined they were not suitable for standard therapy options are eligible
Documented objective radiographic or clinical disease progression on two previous lines of standard therapy
Has been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb).
At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2)
Patients must have received standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy
Standard chemotherapy/trastuzumab declined by patient OR patient is deemed by physician for any reason to not be a candidate for standard therapy (i.e. patient and/or provider choose not to pursue standard trastuzumab-based chemotherapy regimen because of concerns related to toxicity or patient preference)
Have histological or cytological diagnosis of locally advanced/metastatic HER2 solid tumors that has progressed or become intolerant to standard therapy or for which no standard therapy is available
Subject is a candidate for high-dose therapy and autologous SCT based on standard criteria at the institution where this treatment will be administered
Advanced or metastatic colorectal cancer with no curative options available and progression on previous standard therapy, including an EGFR inhibitor if KRAS wild-type
For the dose-escalation cohorts: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available
For the expansion cohort: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer (TNBC), refractory to any standard therapy, have no standard therapy available, or subjects actively refused any standard treatment and / or if, in the judgment of the investigator, experimental treatment is clinically acceptable.
Dose expansion cohort only: Histological or cytological confirmation of advanced unresectable solid tumors for which no standard therapy is available in patients with a known BRCA germline mutation or those with metastatic triple negative breast cancer without known BRCA mutation; for the paclitaxel cohorts, any solid tumors with potential benefit from this combination and paclitaxel
Must have failed at least 1 standard of care systemic therapy for their malignancy
Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded; for eligibility on this trial, allogeneic stem cell transplantation is not to be considered a standard curative option
Patient with histologically-confirmed Stage IV malignant metastatic adenocarcinoma of the pancreas; (a) who has relapsed from or is refractory to standard therapy and for whom no therapy exists that would be curative or might provide significant benefit or (b) who are intolerant to or refuse standard chemotherapy and, therefore, for whom experimental therapy is a reasonable option.
Dose Escalation Cohort only: Confirmed advanced solid tumor or lymphoma for which standard curative or palliative measures do not exist or are no longer effective; subjects with progressive brain metastases are also eligible. OR Confirmed Histological/cytological hematological malignancy that is refractory to/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists. OR Confirmed high grade glioma (grade 3and4) that is relapsed/refractory to standard therapies and who have progressive disease following radiation therapy. Patients with any number of prior treatments are allowed.
Known standard therapy for the patient’s disease that is potentially curative or proven capable of extending life expectancy
Patients must have histologically confirmed gastrointestinal malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom FOLFOX would be an appropriate therapy
Had received standard treatment (no limitations for prior therapies), and in treating physician’s opinion, no suitable standard treatment is available, or for those subjects who decline chemotherapy
Patients with advanced or metastatic cancer that is refractory to standard therapy or has relapsed after standard therapy
Patients must have biopsy-proven metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy
Patients with locoregional disease that have not received appropriate standard locoregional therapy with surgery and/or radiation therapy
Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy
Prior to randomization, patients with metastatic disease must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or patients have declined to receive standard-of-care therapy
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Subjects must have histologically or cytologically confirmed, IDH1 gene-mutated advanced solid tumors, including glioma, that have recurred or progressed following standard therapy, or that have not responded to standard therapy.
Histologically or cytologically documented locally-advanced and/or metastatic solid malignancy that is incurable, and has failed prior standard therapy or for which standard therapy is not appropriate
Any standard contraindications to myeloablative HSCT per standard of care practices at COH
Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
PHASE I: Participants must have histologically confirmed breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Subjects have already undergone all standard of care surgery appropriate for stage of disease.
Participants must have histologically confirmed malignancy with a RAS mutation (via any Clinical Laboratory Improvement Amendments [CLIA]-certified method) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival at least 3 months
Failed to respond to or relapsed following standard treatment, or declined or was not eligible for standard treatment.
Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:
Must have advanced disease and no standard treatment options as determined by locally/regionally available standards of care and treating physician's discretion
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy that is known to be associated with a survival advantage or have disease for which there is no known standard therapy
Patients must be on standard of care lenalidomide maintenance therapy for at least 6 months at the time of study enrollment.
Patient must require a new pre-treatment biopsy as part of their standard of care work-up
Patient does not require a pre-treatment biopsy as part of their standard of care work- up
other solid tumors (all comers) for which there is no standard systemic therapy and there is a rationale for use of pexidartinib at the Investigator's discretion
For dose escalation part: Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed
Eligibility for dose escalation cohort: histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
Eligibility for dose escalation cohort: Histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective OR solid tumor for which irinotecan monotherapy is considered standard
Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard of care through the entire study period (one year)\r\n* HER2-targeted monoclonal antibody therapy is defined as either trastuzumab monotherapy, or trastuzumab and pertuzumab combination therapy administered per standard of care
Participants must have adenocarcinoma of the prostate that is metastatic or unresectable and for which standard curative options do not exist
Failed standard front-line therapy
Solid malignancy that is refractory to at least one prior line of treatment, or for which no standard therapy exists, is required; one prior line of treatment with irinotecan is allowed
Phase I patients: Histologic documentation of a solid malignancy and who have exhausted available standard medical treatments or for whom no standard treatments are currently available; this includes primary brain tumors
A histologically or cytologically confirmed solid tumor that is metastatic, unresectable, or recurrent and for which standard curative or palliative therapies do not exist or are no longer effective.
Hypercalcemia >2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration, diuretics, calcitonin and/or bisphosphate therapy).
Patient has advanced solid malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded; for eligibility on this trial, allogeneic stem cell transplantation is not to be considered a standard curative option
Failure to respond to standard therapy, or for whom standard therapy does not exist.
Patients with advanced or metastatic cancers with no available standard therapy are eligible to enter the phase 1 portion of this study
Histologically confirmed epithelial ovarian, primary peritoneal or fallopian tube malignancy that is metastatic and for which standard curative measures do not exist
Patients must have histologically confirmed solid malignancy that is metastatic or unresectable or lymphoma, for which standard curative or palliative measures that improve survival by at least three months do not exist or are no longer effective; for the purpose of this study patients with leukemia are not eligible
Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
Patients must have pathologically-confirmed acute leukemia, refractory or relapsed after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available Phase II Only: Patient must have histologically or pathologically confirmed diagnosis of AML based on WHO classification that is refractory after standard therapy, or for which conventional systemic chemotherapy is not reliably effective, or no effective therapy is available. Patients aged 60 years or older with newly diagnosed AML who are not eligible for, or who refuse, standard care are also eligible.
In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
Patient must have a histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective (dose-escalation cohorts only)
Relapsed or refractory after ? 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received Rituximab and alkylating agents.
Patient must have histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma harboring a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation, for which no standard therapy is available, is resistant/refractory to standard therapy, has relapsed after standard therapy, or has no standard therapy that improves survival by at least three months
Patients with advanced solid tumor that is refractory to standard treatment, for which no standard treatment is available, or the patient refuses standard therapy.
Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy available that improves survival by at least three months
The participant has a histologic or cytologic diagnosis of a solid tumor (non-prostate, non-breast) that is metastatic and is refractory to or progressed (or relapsed) following standard therapies, or has disease for which no standard therapy exists; presence of metastatic bone lesion(s) is required
Patients must have histologically confirmed (by the National Cancer Institute [NCI] Pathology Department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are associated with minimal patient survival benefit (as defined the Lymphoid Malignancies Branch physicians or if the patient refuses standard of care treatment); enrollment of patients with tumors that can be safely biopsied is encouraged
Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available
Subjects must have failed at least one previous chemotherapy regimen for metastatic disease if standard therapies exist
Patient is starting standard of care Gemcitabine treatment
Subjects must have a histologically or cytologically confirmed solid tumor that is metastatic, unresectable or recurrent and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have completed standard radiation therapy with concurrent TMZ and must not have evidence of progressive disease on post treatment imaging
Dose Escalation phase: Patients with solid tumors (including melanoma) who have failed or are not candidates for standard therapies of for whom no approved therapy is available
Histologically or cytologically confirmed diagnosis of a solid malignancy with advanced disease that has relapsed, that is refractory to standard therapies, or for which there is not standard therapy, or for which the patient opts not to receive standard therapy; patients with tumor types in which carboplatin and paclitaxel is appropriate as a first-line regimen for advanced disease are eligible
Progressed or not tolerated standard therapy, and no further standard therapy is available
(Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of the Investigator. Subject must have relapsed following or be refractory to standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or alkylator (chlorambucil, bendamustine) based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care, or
(Arm B) relapsed or refractory NHL and require treatment in the opinion of the Investigator. Subject must have histologically documented diagnosis of NHL as defined in the World Health Organization classification scheme, except as noted in the exclusion criteria. Subject must have relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care. Subjects with other lymphoproliferative diseases can be considered in consultation with the Abbott medical monitor.
Known standard therapy for the patient’s disease that is potentially curative or proven capable of extending life expectancy
Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
Candidate for known standard therapy for the patient’s disease that is potentially curative
Evidence of CRPC indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies)
Planned or recent initiation of standard docetaxel therapy; patients may be enrolled after receiving standard docetaxel therapy as long as the patient has not demonstrated evidence of progression for more than 45 days before enrollment (“late enrollers”)
Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Phase I: Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective (or who are intolerant of such therapy)
Advanced solid tumor for which, in the opinion of the Investigator, no other standard or investigational therapy offers greater benefit.
Histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation.
Show objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability (excluding ASPS subjects who have not received prior therapy) within 6 months of enrollment.
Progression on or following, or intolerant of, at least one prior line of standard systemic therapy for advanced or metastatic gastric or pancreatic cancers.
Progression on or following, or intolerant of, at least two prior lines of standard systemic therapy for advanced or metastatic colorectal cancers.
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
Completed all acceptable therapies with curative intent that are the current standard of care for their respective diseases. If no conventional therapy available, patient may participate after review by sponsor.
Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed standard of care therapy
Subjects must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy
Patients in whom surgical excision of the tumor is part of standard of care management
Solid tumors refractory to standard therapy
Any available standard line of therapy known to be life-prolonging or life-saving
Patients must be planning to undergo standard of care treatment with surgery and radiation therapy.
ELIGIBILITY CRITERIA – RECIPIENT ON STANDARD CARE THERAPY
In investigators opinion, no curative standard therapy exists
Patients with histologically confirmed solid tumors who: o Part 1: have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy
Patients must have histologically or cytologically confirmed AML, other than acute promyelocytic leukemia, as defined by the 2008 World Health Organization (WHO) criteria that have relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy; subjects >= 60 years of age with newly diagnosed AML who are not candidates for or have refused standard chemotherapy are eligible
Patient is expected to undergo autologous HPC transplantation that is consistent with standard of care
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
Has a histologically- or cytologically-confirmed advanced malignancy that has progressed after standard-of-care therapy/treatments and there is no available therapy likely to convey clinical benefit
Subjects with histologically confirmed relapsed or treatment refractory AML with the exception of subjects who are in first relapse following a remission >12 months in duration and are eligible for standard therapies (e.g., chemotherapy or stem cell transplantation).
Subjects must have no alternate therapy of proven benefit or have refused standard therapy.
Patients must have histologic or cytologic confirmation of cancer for which there is no known standard therapy capable of extending life expectancy
Diagnosis of one of the following advanced solid tumors for which standard therapy either does not exist or has proven ineffective, intolerable or inacceptable for the participant: NMC;TNBC; NSCLC; or CRPC
Part 1: Subjects with solid tumors that are refractory to, relapsed after or intolerant to standard therapy, or for whom no standard therapy exists or who are considered by the investigator to be inappropriate for standard therapy.
Tumor progression following at least one prior standard therapy
Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
Stage IIB-IV mycosis fungoides and Sezary syndrome who have failed at least one standard systemic therapy or are not candidates for standard therapy; (pathology should be reviewed and diagnosis confirmed at Thomas Jefferson University Sidney Kimmel Cancer Center)
Confirmed relapsed or refractory locally advanced or metastatic solid cancer for whom no standard therapy is considered appropriate, or for whom standard therapy is considered intolerable.
Subjects must have histologically or cytologically confirmed locally advanced or metastatic solid tumors and must be refractory to any standard therapy, or have no standard therapy available, or have actively refused any standard therapy or, in the investigator's opinion, experimental treatment in this study is clinically and ethically acceptable for the subject.
Subjects with advanced, histologically or cytologically confirmed tumor, refractory to any standard treatment, with no standard therapy available, in whom standard therapy is not a therapeutic option or the subject actively refuses use of chemotherapy which would be regarded standard and/or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
Subjects with advanced, histologically or cytologically confirmed solid tumors described to express fibroblast growth factor receptor 2 (FGFR2) that are refractory to any standard therapy
For maximum tolerated dose (MTD) Dose Expansion: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer who had undergone within 4 lines of systemic anti-cancer treatment and not eligible for standard therapy anymore.
Subjects with pathologically documented AML that has failed standard treatment, or subjects without prior therapy who refuse standard treatment options
Patients for whom no standard curable therapy exists
Advanced or metastatic solid tumor that has progressed or was not responsive to standard therapy
Dose Escalation Phase: Have a documented diagnosis of a lymphoid hematological malignancy as described by the 2008 World Health Organization (WHO) classification that requires therapy and for which there is no standard of care or standard of care is not expected to be effective. Subjects must not be candidates for anti-tumor regimens known to provide clinical benefit. MM Dose Expansion Cohort:
Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B)
Phase I: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by modified RECIST version 1.1 who have progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, who have tumors harboring one of the following: confirmed PIK3CA mutation or amplification, PTEN loss of function, EGFR mutation, cMET activation and/or HER2 overexpression. Endometrial carcinoma will not be selected for any molecular status.
Phase II: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by modified RECIST version 1.1, who progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, fitting in one of the following groups: Group 1: patients with PIK3CA mutated or amplified ER positive (ER+) breast cancer ; Group 2: patients with endometrial carcinoma (not selected for any molecular status); Group 3: patients with solid tumors (with the exception of PIK3CA mutant/amplified ER+ breast cancer and endometrial carcinoma) harboring PIK3CA mutation or amplification/any PTEN status; Group 4: patients with solid tumors (with the exception of endometrial carcinoma) harboring PTEN loss of function/ PIK3CA wild type; Group 5: non-small cell lung cancer harboring cMET activation and/or EGFR mutation. Up to 3 lines of chemotherapy allowed in advanced/metastatic setting.
Patients with locally advanced or metastatic solid tumors who have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; is not a candidate for, or is unwilling to undergo, standard therapy in cases where no curative option exists.
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
In addition to inclusion criteria listed for Part 1, Part 2 will enroll GCB-DLBCL tFL and MM subjects only. Relapsed and/or refractory MM or tFL that have failed prior standard therapy and for which there is no standard salvage regimen
Pathologically proven diagnosis of breast cancer with clinical evidence of recurrent disease on the chest wall following treatment that included radiotherapy, and for which there is no current standard of care or curative resection able to be performed
Ability to undergo standard induction chemotherapy
Advanced malignancy, metastatic or unresectable, that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which subject is not a candidate for, or is unwilling to undergo, standard therapy.
are eligible for any standard therapy known to be life prolonging or life saving
Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease
Pathologically confirmed advanced G/GEJ/E adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which subject has received prior therapy for advanced disease, for which no standard therapy exists, or subject refuses standard therapy
Subjects with a histologically or cytologically confirmed diagnosis of solid tumors, advanced or metastatic, refractory to or relapsed from standard therapies or for which there is no known effective treatment
Willing to receive their standard multimodality therapy at Mayo Clinic, Rochester
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for which no standard therapy is available.
Subjects with pathologically confirmed colorectal carcinoma that is metastatic or unresectable and which is refractory to standard therapy. To be considered refractory, a subject must have experienced progression (or intolerance) after treatment with standard approved regimens including, oxaliplatin, irinotecan flouropyrimidine, bevacizumab, and cetuximab or panitumumab if KRAS wildtype.
SCREENING: Patients must have received or refused first line standard systemic therapy for their metastases
Male or female patient with Glypican 3 positive advanced solid tumor not amenable to standard therapy or for which standard therapy is not available or not indicated
For Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2a:
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2d:
Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2e:
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Candidate for neoadjuvant chemotherapy with a standard of care, anthracycline-based regimen (Cohort 2 preferred over Cohort 1)
Patients must have histologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have either progressed on least one standard therapy or there must be no standard treatment exists that has been shown to prolong survival for the patient’s disease; patients may have received any number of prior cytotoxic agents
Enrollment into Arm B will be permitted if ibrutinib is considered the standard of care in the clinical practice. EXPANSION COHORT 2 OF ARM C:
Part 1, Part 2b, Part 2d, and Part 2e: Patients with advanced solid tumors who have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy.
Patients with a diagnosis of advanced unresectable non-hematological malignancy that has no known standard of care or for which the use of gemcitabine plus cisplatin constitutes a reasonable option
Patients must have prostate cancer that is advanced or recurrent and for which standard curative or reliable palliative therapies do not exist or are no longer effective
Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
Subjects with advanced, histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available, or subjects actively refused any standard treatment and / or if, in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
Histologically or cytologically confirmed diagnosis of solid malignancy, for which no standard curative or life prolonging therapy is available.
Participants for whom no further standard of care therapy exists, must have received standard of care chemotherapy in the adjuvant or advanced/metastatic setting
Standard (i.e., includes at least taxane + anthracycline) NAC and definitive surgery planned; (NOTE: NAC chemotherapy will be per standard of care, and not dictated by this clinical trial)
Operable tumor >= 1 cm by standard two dimensional (2D) ultrasound (largest unidimensional measurement) and less than 9 weeks after completion of standard NAC
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator.
No standard care available
PLD at the dose and schedule being used might be considered standard of care
Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
Patients with recurrent metastatic or locally advanced disease considered refractory or intolerant to all standard treatment available for their tumor, or those tumors for which no standard treatment is available
Advanced/metastatic solid tumor refractory to standard therapy
Pathologically-documented, definitively-diagnosed AML that is relapsed or refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy
progressed or recurred despite standard therapy
no standard therapy exists
patient is intolerant of standard therapy
patient is not a candidate for standard therapy
Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
At least two-weeks since receipt of prior standard or investigational therapy
Subjects scheduled for VATS lobectomy in accordance with their institution's Standard Of Care;
Participants who have failed at least one line of systemic therapy for advanced stage HCC or participants who are ineligible or unable to tolerate the standard of care treatment.
Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy. Patients must have measurable disease
Hemodynamically stable, consistent with standard of care values for patients undergoing elective tumor resection
Patient willing to undergo scheduled standard of care TRUS guided biopsy
Subject had histologically or cytologically confirmed diagnosis of advanced solid tumor (measurable or nonmeasurable disease) for which no standard therapy is available.
Patients must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, for which standard curative measures do not exist, that has progressed on at least one line of standard therapy or for which no standard therapies exists
Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment.
Group 1: Histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available
Subject must have advanced and/or metastatic, histologically or cytologically documented cancer or lymphomas, for whom there is no available standard therapy shown to provide clinical benefit.
For those receiving bevacizumab, standard medical exclusionary conditions apply
All patients must have received prior first line standard therapy or declined standard therapy, and have been either non-responders (progressive disease) or have recurred
Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
Refractory to or intolerant of standard systemic therapy, including having received two or more standard available therapies known to prolong survival for which s/he was eligible, including leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) with or without bevacizumab, aflibercept, cetuximab or panitumumab
Histologically or cytologically confirmed advanced solid tumor, including glioma, or angioimmunoblastic T-cell lymphoma (AITL) that has recurred or progressed following standard therapy, or that has not responded to standard therapy
Use of any other standard or experimental therapy within 14 days of starting study therapy
Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment does not exist or is no longer effective or tolerable.
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available.
Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
- The remaining standard available therapy as recommended by investigator is best supportive care (note: previous treatment with regorafenib and TAS 102 are allowed and these agents should be administered before study if available to patient according to local standards)
Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
Must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is deemed appropriate for treatment with 1 of the 2 chemotherapy regimens in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable or measurable.
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, and for whom no standard treatment is available.
Histologically or cytologically confirmed diagnosis of solid tumor malignancy that is not responsive to standard therapies or for which there is no approved or curative therapy.
Part I Histologically- or cytologically-confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exist. Part II Arm A have head and neck cancer or K-Ras wild type EGFR expressing colon cancer, Arm B, have non small cell lung cancer, Arm C, have BRAF V600E mutated melanoma and Arm D have HER2 positive breast or gastric cancer that has progressed following one or more treatments for advanced or metastatic disease.
Histologically- or cytologically-confirmed melanoma or clear-cell RCC that are refractory to standard therapy or for which no standard therapy exists
Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy
Advanced or metastatic solid tumor refractory to standard therapy
Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors who are not candidates for standard therapy or in whom regorafenib or cetuximab is considered a standard treatment. Patients with metastatic colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis available and no K-ras mutation is present.
Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
Histologically/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
Patients must have histologic or cytologic evidence of a solid neoplasm for which no standard therapy is available, or have progressed despite standard therapy, or are intolerant to standard therapy.
For dose escalation cohorts: Subjects with advanced, histologically or cytologically confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory to standard treatment with no standard therapy available, or subjects actively refuse any treatment, which would be regarded standard. In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable
Patients with a malignancy that is either refractory to standard therapy or for which no standard therapy is available.
Patients must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3 chemotherapy regimens in this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable
Part 1 only: Patients with histologically or cytologically proven progressive or metastatic solid tumors who have failed standard treatment and have no other effective treatment available. Part 2 only: Patients with histologically or cytologically proven progressive or metastatic solid tumors who have failed standard treatment and have no other effective treatment available, or docetaxel-naive patients who have failed standard treatment and have tumors for which a docetaxel-based regimen would be appropriate.
Progressed or refractory to at least 1 prior line of standard therapy
Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.
Arm 1 only: Histologically confirmed malignant solid tumor which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment
Arm 2 only: Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the colon or rectum which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment
Advanced malignant solid tumors for which no curative therapy exists that has recurred or pgrogressed following standard therapy
Pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or which no standard therapy is available, or the subject refuses standard therapy or multiple myeloma
Pathologically confirmed solid tumor, locally advanced / metastatic, refractory after standard therapy, or for which no effective curative or surgical treatment options are available
Histologically or cytologically confirmed solid tumors known to express C4.4a (eg, carcinomas of the lung, head & neck SCC, esophagus SCC (squamous cell carcinoma),colon, ovary, prostate, and breast) that are refractory to any standard therapy, or have no standard therapy available, or for which subjects actively refuse any treatment that would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.
Must have a disease that is relapsed/refractory to all potentially curative standard treatment regimens or must have a current disease for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
Progressed, or been intolerant to, at least one standard treatment regimen
Not eligible for or declined transplantation or any standard therapy known to be life prolonging or life saving
Relapsed or refractory disease (as defined below) for which patients are ineligible for or have exhausted standard therapeutic options that would be considered standard of care
Histologically- or cytologically-confirmed advanced/metastatic solid tumor or lymphoma that is refractory to standard therapies, or the patient refuses standard therapy
Participants with histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care
Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist
Tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists
Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months
Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
Histologic proof of cancer for which no standard therapy is available, and which shows no staining for RB by IHC.
Subjects must have a pathologically documented, definitively diagnosed, clear cell RCC that is relapsed/refractory following at least two lines of systemic therapy (one of which must be a tyrosine kinase), or the subject refuses standard therapy
RCC patients only: Tumor progression after receiving standard/approved chemotherapy and/or targeted agent, where there is no approved therapy or for tumors where sorafenib based therapy would be standard therapy (Phase I)
Histologically or cytologically documented, incurable, locally advanced or metastatic solid tumors or recurrent malignant lymphoma in subjects who failed standard therapy or for whom standard or curative therapy does not exist or is not tolerable.
locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy.
Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months if available
Subjects with advanced or metastatic solid tumors (non-hematologic refractory to or relapsed from standard therapies or for which there is no known effective treatment during dose escalation
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
Phase I: Diagnosis of recurrent, metastatic or primary unresectable solid tumor that does not have curative standard treatment
Diagnosed with advanced refractory solid malignancies or intolerant of standard therapy for the stage of the disease (because there is currently no standard approved therapy for adenoid cystic carcinoma, therefore there is no requirement of prior therapy for this patient population)
Dose-escalation stage: Participants with histologically documented incurable, locally advanced, or metastatic epithelial malignancy that has progressed despite standard therapy or for which no standard therapy exists
Expansion stage: Participants with one of the following epithelial, histologically-documented, incurable, locally advanced, or metastatic tumor that has progressed despite standard therapy or for which no standard therapy exists: CRC, NSCLC, HNSCC, or pancreatic cancer
65+ yrs with AML not eligible for standard frontline chemo
Patients with metastatic renal cell carcinoma referred for the study may not be eligible for the experimental protocol therapy due to reasons such as uncertainty about donor HLA typing or need to control malignant disease, infection, or metabolic abnormality such as hypercalcemia on an emergent basis; should a referred patient present to us in such a scenario, the patient will be referred back to their primary hematologist-oncologist for treatment; however, if referral back to the referring physician is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease or complicating conditions (infection, metabolic problems) under the current study; if it becomes apparent that the patient will not be able to proceed to experimental therapy, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol; it is not necessary to complete the eligibility criteria prior to receiving such standard care; however, prior to initiation of the experimental therapy (starting with the pentostatin-cyclophosphamide [PC] regimen), the patient must meet each of the eligibility criteria
Patients must have completed standard frontline therapy for newly diagnosed metastatic disease; lung, bone, bone marrow or other metastases are sufficient to qualify as metastatic disease; standard frontline therapy is comprised of a regimen that includes (but is not limited to) multiple cycles of vincristine, adriamycin, ifosfamide, and etoposide; local therapy as dictated by the treating institutions; patients may have received autologous stem cell transplantation or other investigational agents as part of their primary therapy
Disease that has progressed despite other available standard treatment options, based on what is clinically indicated according to the investigator's clinical and medical judgment, including:
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or has no standard therapy that improves survival by at least three months
Solid tumor, including central nervous tumors, that is recurrent or refractory to standard therapy or for which standard therapy is not available; all research participants must have a pathologic diagnosis either from their initial presentation, or at the time of recurrence or progression; the requirement for histologic verification may be waived for patients with brainstem glioma and optic pathway glioma
All patients in both group 1 and 2 will also be referred to radiation and medical oncology for standard of care adjuvant therapy with or without PDT therapy
The patient received induction and consolidation therapy according to the Institution's standard of care.
Histologically or cytologically confirmed solid tumor that has recurred after standard therapy, or for which there is no standard therapy. Subjects with brainstem glioma DO NOT need histologic proof of the diagnosis.
Must be planning to undergo standard radiation therapy.
Histologically confirmed medulloblastoma located in the posterior fossa            \r\n* Standard-risk disease
Patients with bilateral pulmonary metastases from sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura who can be rendered no clinical evidence of active disease (NED) or minimal residual disease (MRD) by standard of care metastasectomy where NED refers to diagnostic tests failing to detect presence of disease and MRD refers to low-volume, subclinical disease which is not amenable to standard of care biopsy for histologic confirmation and poses no immediate threat to patient health and would not otherwise warrant standard of care treatment but surveillance instead
Patients must have received first line standard systemic therapy for their metastases (if applicable)
Patients with locally advanced or metastatic HPV associate malignancy (cervical, vaginal, vulvar, penile, anal, or oropharyngeal carcinoma), either refractory to standard therapy or for which no effective standard therapy that confers clinical benefit is available
For the dose escalation cohort, patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
For the dose expansion cohort, participants must have histologically or cytologically confirmed diagnosis of either: i) ovarian, fallopian tube, or primary peritoneal cancer of high grade serous histology which has recurred despite standard therapy or ii) triple-negative breast cancer which has recurred despite standard therapy
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have previously received standard systemic therapy for advanced thyroid cancer (to include radioactive iodine for iodine-avid tumors and surgery [if indicated]) and have been either non-responders (progressive disease) or have recurred
COHORT C SPECIFIC INCLUSION: Histologically confirmed IDH mutant glioma, meningioma, or ependymoma that has recurred despite previous standard of care therapy; because this cohort is, in part, meant to allow patients access to therapy who might not otherwise be eligible for other clinical trials - deviations from standard of care treatment can be presented to and approved by the principal investigator for inclusion in the study
No other investigational or standard anti-tumor therapy allowed
on maintenance standard-of-care chemotherapies or on treatment holiday
Relapsed or refractory to greater than or equal to (>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator
Participants who are refractory or relapsed after at least 1 prior line of therapy and for whom no effective standard therapy is available per the investigator's assessment.
Participants must have disease that is relapsed or refractory and for which standard curative or palliative measures do not exist or are no longer effective
Completed curative intent therapy, without additional standard of care curative intent therapy feasible within 20 weeks prior to study enrollment
Measurable disease that is amenable to curative intent therapy, or amenable to standard of care systemic/palliative therapy (e.g. platinum containing chemotherapy, cetuximab, pembrolizumab or other approved options)
Progressive HER2 positive solid tumours (immunohistochemistry [IHC] positive or equivocal) with no available standard or curative treatment.
Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists; exceptions: NSCLC, head and neck squamous cell cancer (HNSCC), bladder cancer, MSI-H/dMMR cancers and melanoma expansion cohorts in Part 2B pembrolizumab combination. 1) Subjects must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Subjects who received prior anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) therapy must have received at least 4 months of treatment (Part 1B and Part 2B).
Estimated intelligence at least 80 (standard score)
Diagnosis of glioblastoma requiring standard care chemoradiation of concurrent Temozolomide and 60 gray (Gy) of radiation given over 30 treatments
Willing to be randomized to either standard care or intervention group
Unwilling to be randomized to either standard care or intervention group
Meet standard clinical criteria for being a caregiver (able to drive and take care of patient)
Patients undergoing a cord blood or haploidentical transplantation on any protocol or standard of care treatment plan
Tumor for which prior treatment has proven to be ineffective or intolerable or for which no standard therapy exists
Phase I-Ib part (including dose ranging part): Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST v1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists and who did not receive prior anti-PD-1/PD-L1 treatment.
Phase II part (MBG453 single agent): Patients with advanced/metastatic solid tumors in the indication in which at least one confirmed PR or CR was seen during the dose escalation phase I part. Patients must have measurable disease as determined by RECIST v1.1, have progressed despite standard therapy or be intolerant to standard therapy.
Phase II part (MBG453 in combination PDR001): Patients with advanced/metastatic tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1, who have received standard therapy and are intolerant of standard therapy or have progressed following their last prior therapy.:
Dose escalation: patients must have histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable and for whom either standard curative or palliative measures do not exist or are no longer effective, or for whom anti-PD-L1/cytotoxic T-lymphocyte antigen (CTLA)-4 is appropriate
(Part A only) Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which no standard therapy exists, or who are not eligible for standard treatment. Subjects must have received at least one prior therapy for their malignancy;
For all arms except Arm L (pembrolizumab) and Arm M (nivolumab), patients must have failed prior standard curative chemotherapy for their disease; subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
Participant in the dose escalation cohorts must have histological confirmation of locally advanced or metastatic solid tumor that is either refractory after standard of care therapy for the disease or for which standard of care therapy or does not exist.
Participants in the expansion cohorts must have histological confirmation of AML, Multiple Myeloma, breast cancer, NSCLC, prostate cancer, SCLC, or NHL that is either refractory after standard of care therapy or for which standard of care therapy does not exist.
Patients will receive standard of care systemic treatment for underlying solid malignancy as deemed necessary by treating physician
Patients who qualify for pulmonary rehabilitation as part of the standard of care and are covered by medical insurance
Scheduled to undergo bronchoscopy for malignant airway obstruction as standard medical care
Is pregnant (confirmed by the patient as imaging clinic standard of care) or nursing mother
Eligible for at least 2 cycles of standard of care AML chemotherapy that will result in moderate to severe myelosuppression and have curative intent
For the dose escalation cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 2 prior standard treatment regimens or standard treatment was declined.
For the dose expansion cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 1 prior standard treatment regimen or standard therapy was declined.
Intolerance to at least 2 prior standard therapy regimens
Completion of primary standard of care breast cancer therapies (i.e., surgery, chemotherapy, immunotherapy and radiation therapy as appropriate per standard of care for patients' specific cancer)
Is pregnant (confirmed by the patient as imaging clinic standard of care) or nursing mother
Radiation to the recurrent or metastatic site is clinically indicated and would be considered standard care for palliation or for locoregional control
Lung cancer patients receiving definitive radiation therapy defined as 45-75 Gy as part of  standard of care for their disease
Patient must be expected to undergo therapy with bevacizumab in combination with paclitaxel at recommended standard of care doses if suspected recurrence is confirmed with imaging
Planned standard of care surgery
Planned standard of care surgery with curative intent for pancreatic adenocarcinoma
Eligible for anti-EGFR monoclonal antibody (mAb) therapy as standard-of-care (SOC), either as a single agent or in combination with approved irinotecan-containing regimens
Subjects for whom participating would significantly delay the scheduled standard of care therapy
Subjects for whom participating would significantly delay the scheduled standard of care therapy
Standard of care CT abdomen examination planned with intravenous (IV) contrast.
Have standard of care biopsy or resection planned or tumors amenable to serial biopsies.
Participating would significantly delay the scheduled standard of care therapy
Scheduled for contrast CT (standard of care)
Any condition that excludes SLN biopsy as the standard of care (e.g. lymphadenectomy indicated)
Is pregnant (confirmed by the patient as imaging clinic standard of care) or nursing mother
fMRI and/or DTI required for preoperative imaging as part of the standard of care
Scheduled to receive therapy with trastuzumab plus chemotherapy as part of standard care
Scheduled to receive pre-operative therapy with trastuzumab plus chemotherapy as part of standard care
Planned standard of care surgery with curative intent for pancreatic adenocarcinoma
Declined all standard treatment options
Known lung lesion(s) based on standard of care (SOC) non-contrast CT
Participants enrolled in other therapeutic protocols are eligible, except protocols involving a VEGF-receptor (R) inhibitor or radiation therapy outside the standard of care
Has progressed after prior therapy and either a) there is no further effective standard anticancer therapy available (including subject refusal) or b) is intolerant to standard anticancer therapy.
Relapsed or refractory disease after a systemic standard of care treatment regimen and, if available, at least one standard of care salvage regimen
Histologically confirmed advanced malignancy defined as any of the following tumors for which no further standard or curative therapy exists or is considered appropriate by the Investigator:
Progressive disease following or intolerant of or refuses standard of care systemic therapy
Relapsed or refractory malignant solid tumors of any histology for which no standard curative therapy is available (escalation phase).
Patients with histological- or cytological-confirmed, advanced unresectable breast, gastric, or non-small cell lung cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists. a. Part C: Only the following subtype of tumors with the molecular/genetic alterations will be enrolled: HER2 positive MBC Advanced NSCLC, harboring EGFR mutations after progression on osimertinib Advanced NSCLC, harboring ALK translocations after treatment with alectinib or at least 2 ALK inhibitors
Patients must have been referred for repeat tumor biopsy as part of standard care and the biopsy must have been approved by the appropriate biopsy service (interventional radiology or surgery); such approval includes review of medical history and laboratory parameters as per standard care
Planned standard of care surgery
Patients must be scheduled to receive: 1) standard chemotherapy with/without radiation therapy; OR 2) single-agent bevacizumab (Avastin)
Subjects for whom participating would significantly delay the scheduled standard of care therapy
Participation would significantly delay the scheduled standard of care therapy
Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons
Physicians determine that OCT investigation will not alter standard of care for the patient
Patient who will undergo standard of care clinical staging for UTUC
Participants with hepatocellular carcinoma or Intrahepatic Cholangiocarcinoma (ICC) who have progressed despite standard therapy or are intolerant of standard therapy
Plan to begin trabectedin as standard of care
Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Confirmed locally advanced and/or metastatic solid tumor in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
Has failed standard treatment
Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least one of the following:
Participants must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor(s) appropriate for treatment with one of the 2 combination therapies in Part B of this study, have progressed despite standard therapy, or for whom conventional therapy is not considered effective.
For Part B only, participants must have advanced or metastatic CRC expressing either low or high levels of GCC, for whom standard treatment is no longer effective or does not offer curative or life-prolonging benefit. A portion of participants should have tumors amenable for serial biopsy and a willingness to provide consent for pharmacodynamic assessment.
Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:
Adult participants who have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that is appropriate for treatment with either docetaxel or carboplatin + paclitaxel in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable.
In the Dose Escalation Segment, patients who are refractory, relapsed, or unresponsive to standard treatment.
Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate for definitive multimodality therapy) or stage IV NSCLC demonstrated ALK-positive or an advanced tumor, other than NSCLC, that carries an ALK genetic alteration (mutation, translocation or amplification) and/or ALK overexpression that has progressed despite standard therapy, or for which no effective standard therapy exists.
The participant has histologically or cytologically advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
The participant has histologically or cytologically confirmed advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
Must have a histologically or cytologically confirmed metastatic and/or advanced solid tumor and/or lymphoma for which standard curative or life-prolonging treatment does not exist, or is no longer effective or tolerable.
Subjects will be screened and excluded per standard clinical protocol
Ineligible for or have exhausted standard therapeutic options
Must have received and progressed on or failed one standard/approved treatment for cancer type, if available
Histologically or cytologically confirmed non-CNS solid tumor that recurred after standard/frontline therapy, or for which there is no standard/frontline therapy available.
Patients with advanced cancer who are refractory to, have demonstrated intolerance to, or have refused access to, available standard therapies
Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients with relapsed or refractory disease with no available standard therapy
Patients must have histologically confirmed solid tumors for which standard therapy known to prolong survival has failed in the metastatic setting or for which standard therapies do not exist
Histologically documented, metastatic NSCLC that has failed at least one standard therapy
Subject must have metastatic or recurrent disease and have failed first-line systemic treatment, and if indicated, failed approved second-line therapy, and for whom no standard therapy options are anticipated to result in a durable remission