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+Patients in both cohorts must have progressive disease following prior therapy; specifically:\r\n* Cohort 1 (NSCLC): Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; this includes patients who demonstrated an initial response and subsequent progression; no prior treatment with chemotherapy or targeted agents are required; intervening therapy is allowed between previous PD-1 directed treatment and there is no required interval from prior PD-1 treatment required; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as MEDI4736 (durvalumab), atezolizumab and avelumab; these agents may have been administered as part of a clinical trial\r\n* Cohort 2 (colorectal cancer): Patients must have progressed on >= one line chemotherapy
+Prior exposure to immune-mediated therapy, including durvalumab and tremelimumab, except for anti-PD-1 or anti-PD-L1 therapy (including durvalumab) in NSCLC patients; this includes anti-CTLA-4 agents (prior treatment with these agents is NOT allowed in either cohort) and, excludes therapeutic anticancer vaccines, excluding therapeutic anticancer vaccines; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
+Patients who have received prior anti-PD1 directed therapy (monoclonal antibody [mAb] or small molecule) are not eligible
+No prior treatment with any therapy on the PD-1/PD-L1 axis
+No prior anti-MET therapy such as crizotinib or cabozantinib, or PD-1/PD-L1 immune checkpoint inhibitor therapy (such as nivolumab, pembrolizumab, atezolizumab) or CTLA4 inhibitor therapy (such as ipilimumab); no prior allergic reaction to small molecule tyrosine kinase inhibitors or monoclonal antibodies\r\n* Exception for targeted therapy sub-study (Arm T): Prior crizotinib may be allowed depending on the gene alteration
+Patients who have received prior therapy with midostaurin, any anti-PD-1 or anti-PD-L1 therapy, any deoxyribonucleic acid (DNA)-methyltransferase inhibitor (including hypomethylating agents such as azacitidine, decitabine, or other investigational agent that acts by inhibiting DNA or ribonucleic acid [RNA] methylation) for any condition, or prior intensive cytotoxic therapy for myelodysplastic syndrome (MDS), are not eligible
+Participants may not have received any prior treatment with therapies targeting PDL1, PD1 or CTLA4
+Prior PD-1- or PD-L1-directed therapy.
+Prior treatment with an agent that blocks the PD-1/PD-Ligand 1 pathway;
+Radiological progression (confirmed at least 4 weeks after the initial scan showing PD); or
+Cohort A Dose Expansion (Ribociclib + PDR001): Treatment with prior PD1/PDL1/CTLA4 is prohibited
+Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Treatment with prior PD1/PDL1/CTLA4 inhibitors are prohibited
+Prior therapy with a PD-1, PD-L1, PD-L2 or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy
+Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints), such as PD-1, PD-L1, or cytotoxic T lymphocyte antigen-4.
+Key Inclusion Criteria Part 1:\n\n          -  Patients with advanced (unresectable) or metastatic solid tumor and have disease\n             progression after treatment with available therapies that are known to confer clinical\n             benefit or who are intolerant to treatment.\n\n          -  Patients must have tumor tissue available.\n\n          -  Female patients must have a negative serum or urine pregnancy test or be of\n             non-childbearing potential.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to\n             1 and adequate organ function.\n\n        Key Inclusion Criteria Part 2:\n\n        - Patients must have not been previously treated with an anti - LAG - 3, anti - PD - 1,\n        anti - PD - L1, or anti - PD - L2 antibody.\n\n        Key Exclusion Criteria for all:\n\n          -  Known uncontrolled central nervous system metastases and - or carcinomatous\n             meningitis.\n\n          -  History of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C.\n\n          -  Participated in another investigational study (drug or device) within 4 weeks of first\n             dose.\n\n          -  Received prior anticancer therapy within 21 days of first dose.\n\n          -  Not recovered from Adverse Events (AEs) and - or complications from major surgery\n             prior to first dose.\n\n          -  Vaccine within 7 days of planned start of study treatment.
+Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40
+Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II expression
+Histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with anti-PD-1/PD-L1 therapy. Subjects with BRAF activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor regimen prior to anti-PD-1/PD-L1 therapy.
+Previous exposure to any immunomodulatory agents (e.g., anti- CD40, CTLA-4, PD-1/PD-L1, IDO inhibitors) or any other immunomodulatory agent (with the following (except PD-1/PD-L1 in subjects with unresectable or metastatic melanoma)
+History of life-threatening toxicity related to prior anti-PD-1/PD-L1 treatment for subjects with metastatic melanoma
+Refractory to prior anti-PD-1/PD-L1 agent
+Previous therapy with any PD-1 or PD-L1 inhibitor including durvalumab or anti-CTLA4 (including tremelimumab) for any malignancy.
+Prior anti-PD-1 treatment for combination dose expansion cohorts 3a - 3d
+Intolerance to prior anti-PD-1/PD-L1 therapy
+Prior anti-PD-1 treatment for combination dose expansion cohorts 3e - 3h
+Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.
+Patient has received prior immunotherapy with inhibitors of PD-1/PD-L1 axis
+Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade.
+Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) study
+Prior treatment with the following agents (from last dose of prior treatment to first dose of GSK3174998): Tumor necrosis factor receptor (TNFR) agonists, including OX40, CD27, CD137 (4-1BB), CD357 (GITR): at any time; Checkpoint inhibitors, including PD-1, PD-L1, and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors: within 4 weeks.
+For solid tumors other than melanoma, (in Part 4 or 5 [dose confirmation only]), participants must have a malignancy that is incurable and has either: (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participants and treating physician. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds targeting programmed cell death 1 (PD-1), PD-1 ligand 1 (PD-L1), BRAF, or mitogen-activated protein kinase (MEK). Treatment must end at least 4 weeks prior to randomization.
+Prior therapy with compounds targeting PD-1, PD-L1, BRAF, mitogen-activated protein kinase (MEK) or other molecules in the mitogen-activated protein kinase (MAPK) pathway
+Prior treatment with a PD-1/PD-L1 inhibitor
+Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent
+Prior therapy with an immune checkpoint inhibitor therapy is allowable. A 6-week washout period will be required for those with prior PD-1 or PD-L1 treatment.
+For patients with mCRPC, prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway.
+Patient may be second- or later-line NSCLC patient, and must have documented radiological and/or clinical progression on a prior anti-PD-1/PD-L1 containing therapy.
+Prior treatment with a platinum-based (cisplatin or carboplatin) regimen and a PD-1 or PD-L1 monoclonal antibody (either in combination or sequentially).
+Prior treatment with a PD-1, PD-L1 or PD-L2 inhibitor
+Prior PD-1/PD-L1 treatment is permitted in Part B of this study, but only subjects who have progressed on their prior PD-1/PD-L1 treatment without a partial or complete response, and without discontinuing for drug-related toxicity are eligible for Part B.
+Patients undergoing elective pancreatoduodenectomy (PD) for any diagnosis/indication
+Patients undergoing a minimally invasive PD, such as laparoscopic or robotic PD
+Prior therapy with any of the following: PD-1, PD-L1, CTLA4 antibody, or any other drug targeting T cell checkpoint pathways.
+For Phase 1a and 1b, prior PD-1 or PD-L1 therapy or other immunotherapy is allowed, if the following criteria are met:
+Prior treatment with PD-1 or PD-L1 inhibitor
+Patients must have evidence of radiologic or clinical disease progression during or within 6 months of previous treatment with systemic PD-1 directed therapy, or have stable disease on prior PD-1 therapy (at least 6 doses) and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as durvalumab; these agents may have been administered as part of a clinical trial, and/or in combination with other immunologic agents such as CTLA-4 inhibitors or other investigational agents
+Previous treatment with a CTLA-4, PD-1, or PD-L1 inhibitor, including prior treatment with either durvalumab or tremelimumab
+Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent
+Previous treatment with atezolizumab or another programmed death-1 (PD-1)/PD-L1 inhibitor
+Prior treatment with anti-PD-1 or PD-L1 therapies
+Inclusion Criteria (Phase 1 and 2 Melanoma and HNSCC patients)\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.\n\n          -  Life expectancy of at least 6 months.\n\n          -  Have provided tissue biopsy sample enough for PD-L1 expression level testing and RNA\n             expression profiling.\n\n        Inclusion Criteria: Phase 2 Melanoma patients\n\n          -  Histologically or cytologically confirmed unresectable or metastatic (stage IV)\n             melanoma.\n\n          -  Have at least 2 sites that qualify as measurable target lesions per RECIST 1.1 of\n             which 1 must be palpable or visualized by ultrasound and easily accessible to multiple\n             intratumoral injections.\n\n          -  For patients with progressive disease (PD) while receiving anti-PD-1/L1 therapy, must\n             have documented PD per RECIST v1.1 while receiving a prior anti-PD-1/L1 therapy.\n\n        Inclusion Criteria: Phase 2 HNSCC patients\n\n          -  Histologically or cytologically confirmed recurrent or metastatic HNSCC that could not\n             be treated with curative intent.\n\n          -  Have at least 1 measurable target lesion per RECIST 1.1, which must be accessible and\n             amenable to multiple intratumoral injections.\n\n          -  Must have documented PD per RECIST v1.1 while receiving a prior anti-PD-1/L1 therapy.\n\n        Exclusion Criteria: (Phase 1 and 2 Melanoma and HNSCC patients)\n\n          -  Received systemic chemotherapy or biological cancer therapy (except anti-PD-1/L1\n             therapy) within 3 weeks prior to study enrollment.\n\n          -  Received prior radiotherapy within 2 weeks of start of study therapy.\n\n          -  Received small molecule inhibitor targeted therapy, such as tyrosine kinase\n             inhibitors, within 2 weeks prior to study enrollment.\n\n          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other\n             form of immunosuppressive therapy (including immune modulators or systemic\n             corticosteroids) within 7 days prior to study enrollment\n\n          -  Is expected to require any other form of anti-cancer therapy while in the trial.\n\n          -  Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).\n\n          -  History of or current uveal or ocular melanoma.\n\n          -  Active infection including cytomegalovirus.\n\n          -  Active autoimmune disease requiring systemic treatment in the past 2 years or a\n             disease that requires immunosuppressive medication. Replacement therapy is not\n             considered a form of systemic treatment.\n\n          -  Current pneumonitis or history of (non-infectious) pneumonitis that required steroids.\n\n          -  Known active central nervous system metastases or carcinomatous meningitis.\n\n          -  Use of any investigational agent within the last 28 days prior to study enrollment.\n\n          -  Has received a live-virus vaccination within 30 days of planned treatment start.\n             Seasonal flu vaccines that do not contain live virus are permitted.\n\n          -  Any known additional malignancy that is progressing or requires active treatment,\n             except for melanoma and HNSCC.\n\n        Exclusion Criteria (Phase 2, Melanoma Expansion Cohorts 1 and 5 only)\n\n          -  Any prior combination therapy targeting immunoregulatory receptors or mechanisms and\n             an anti-PD-1/L1 agent or an investigational agent targeting immunoregulatory receptors\n\n          -  Prior therapy with an anti PD 1/L1 agent\n\n        Exclusion Criteria: (Phase 2, Melanoma Expansion Cohort 2 only)\n\n        • Any prior combination therapy involving agents given by intratumoral injection that\n        target the innate immune pathway or system.\n\n        Exclusion Criteria: (Phase 2, HNSCC Expansion Cohorts 3 and 6 only)\n\n          -  Prior therapy with an anti PD 1/L1 agent\n\n          -  Require treatment on anticoagulation therapy.\n\n        Exclusion Criteria (Phase 2, HNSCC Expansion Cohorts 4 and 7 only)\n\n          -  Any prior combination therapy involving agents given by intratumoral injection that\n             target the innate immune pathway or system.\n\n          -  Require treatment on anticoagulation therapy
+Prior therapy with specific antibody/drug targeting immune or coregulatory or costimulatory proteins (such as checkpoints e.g., PD-1 or PD L1, 4-1BB, OX40 or CTLA-4 antibodies).
+Any prior immunologic cancer therapy with systemic inhibitors of the PD-1 or CTLA-4 pathway
+Patients can be treated either in first line or in the refractory setting; PD-L1 positivity is not required for enrollment
+Patient has received immunotherapy with inhibitors of PD-1 or PD-L1, or CTLA-4 blocking antibodies within 4 months prior to study day 1
+Prior systemic anti-cancer therapy of any kind for RCC, including but not limited to any approved agent or any previous treatment with a PD1 or PD-L1 inhibitor including durvalumab; no previous treatment with immunotherapy for any malignancy including cytokine, anti-tumor vaccine, T-cell activator, co-stimulator or immune checkpoint inhibitor
+Patient must have previously received one (but no more) line of previous therapy with an anti-PD-1/PD-L1 mAb therapy either alone or in combination and have either progressed or responded and then stopped responding.
+Patients must have previously received at least one line (and not more than 2 lines) of previous therapy with an anti-PD-1/PD-L1 mAb therapy, either alone or in combination, and have either progressed or responded and then stopped responding.
+Previous treatment with a PD-1 or PD-L1 inhibitor with documented progression of disease on most recent computed tomography (CT) scan; progression of disease is defined as 1) the appearance of a new measureable lesion (> 10 mm) on cross-sectional imaging or physical exam OR 2) enlargement of previously detected lesions on two consecutive imaging studies OR 3) enlargement of a previously detected lesion with correlative symptomatology on one cross-sectional imaging study; patients remain eligible if they had a previous response to a PD-1 inhibitor, including patients who had a complete response, partial response or stable disease; primary progressing patients are defined as those who received anti-PD-1 therapy within 2 months of study enrollment; patients with relapsed disease are defined as those who received their last dose of PD-1 blocking antibody >= 2 months prior to enrollment
+Patients who received adjuvant PD-1 therapy who then develop measurable disease are eligible; however, they must have received their last dose of PD-1/PD-L1 blockade within two months of enrollment in this trial; they will be stratified with patients who have progressive disease
+Previously treated with a PD-1/PD-L1-blocking antibody or a histone deacetylase inhibitor
+Have available evaluable archival tumor tissue for PD-L1 biomarker assessment; presence of PD-L1 antigen on tumors is NOT required for study entry
+History of severe immune-related adverse effects from CEA-IL2v or anti-PD-1 (nivolumab, pembrolizumab) or anti-PD-L1 (atezolizumab) therapies (Common Terminology Criteria for Adverse Events Grade 3 and 4)
+Patients who are receiving or have been treated with antibody to CTLA4 (e.g. ipilimumab), PD-1, PD-L1, CD137, or CD27 within the prior 12 months. Any patient who has had one or more of these therapies greater than 12 months prior and is clinically free of disease and totally recovered from toxicities related to those therapies can be eligible.
+Grade 3 or 4 major organ immune-related adverse events (IRAEs) following treatment with anti-PD-1/PD-L1
+Having progressed on at least one prior line of therapy, histologically or cytologically confirmed diagnosis of one of the following: \r\n* Dose escalation and expansion cohorts:\r\n** Checkpoint inhibitor naive non-small cell lung cancer patients must have progressed on front-line therapy cytotoxic chemotherapy and may have received up to two prior treatment regimens provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.\r\n** Progressed on checkpoint inhibitor non-small cell lung cancer patients must have progressed on front-line checkpoint inhibitor therapy and may have received up to two prior treatment regimens provided no regimens included an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.\r\n** Thymic carcinoma patients must not be eligible for surgical resection at the time of enrollment and may have received any number of prior lines of therapy provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.
+Phase 1: Patients with histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor who meet one of the following criteria:
+Phase 2: Patients with histologically or cytologically confirmed diagnosis of one of the following and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor:
+For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy;
+Documented disease refractory to at least one PD1/PD-L1 (+/- CTLA-4) inhibitor treatment, or intolerance to these drugs
+Refractory patients who are naïve to anti-PD-1/PDL-1 therapy OR Relapsed after 3 or more lines of therapies; and are naïve to anti-PD-1/PDL-1 therapy OR
+Meet criteria for either the acquired resistance OR the suboptimal benefit cohort\r\n* Acquired resistance is defined as (must both be met):\r\n** Prior benefit from anti-PD-1/PD-L1 therapy defined as a) prior response, and/or b) ? 5 months of stable disease (SD); intervening therapies are allowed\r\n** Progressive disease (PD) on recent scans\r\n* Suboptimal benefit is defined as (must both be met):\r\n** Prolonged stable disease ? 5 months OR suboptimal response (> 10% & < 50% shrinkage per Response Evaluation Criteria in Solid Tumors [RECIST] at any evaluation timepoint) \r\n** Ongoing stable disease on recent scans\r\n** Last treatment with an anti-PD-1/PD-L1 agent within 6 weeks prior to starting protocol treatment
+Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy.
+Patients with prior treatment with PD-1 or PD-L1 inhibitor
+Disease progression on prior PD-1/PD-L1 therapy in any line. Subjects must have received a minimum of 4 doses of anti-PD-1/PD-L1 therapy. If subjects have received fewer than 4 doses of anti-PD-1/PD-L1 therapy, documented radiologic progression and sponsor approval is necessary prior to inclusion.
+14 days for prior PD-1 therapy.
+Prior treatment with any PD-1 or PDL-1 inhibitor
+Systemic immunotherapy for metastatic NSCLC. Immunotherapy agents include, but are not limited to, agents targeting the PD1/PD-L1 axis (e.g. nivolumab, pembrolizumab, atezolizumab, durvalumab) or CTLA-4 (ipilimumab, tremelimumab) pathways.
+Participants who have received previous immunotherapy for any cancer (excluding melanoma) including PD-1/PD-L1 inhibitors but not interferons and CTLA-4 inhibitors
+Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor; prior treatment with cetuximab or a PD-1/PD-L1 inhibitor is allowed as long as not previously given in combination
+Must be pembrolizumab/nivolumab refractory/resistant – defined as having received at least 2 doses of pembrolizumab (or 2 doses of nivolumab) with documented systemic disease progression on staging imaging; progressive disease (PD) will be defined as increase in tumor burden > 20% relative to nadir (minimum recorded tumor burden) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; once PD is confirmed, initial date of PD documentation will be considered as the date of disease progression; patients can be enrolled at any time following initiation of PD-1 therapy up to 1 year
+Patients receiving PD-1 therapy whose disease is responding or stable (as defined by RECIST v1.1)
+Subjects should have PD-L1 expression (tumor proportion score [TPS] >= 50%, determined by the Food and Drug Administration [FDA] approved Merck 22C3 antibody PD-L1 test) in the first-line setting and have a TPS > 1% by 22C3 or equivalent PD-L1 expression by an approved immunohistochemistry (IHC) test, in the second-line setting in order to be eligible for pembrolizumab treatment on the current protocol; patients with < 1% PD-L1 expression are not eligible
+Subjects may already be receiving PD-(L)1 (including pembrolizumab or other PD-[L]1 inhibitors such as nivolumab, atezolizumab, avelumab, durvalumab) for the treatment of systemic disease; systemic disease must be in complete remission or be stable by RECIST 1.1; a washout period of at least 3 weeks is required from the last dose of PD-(L)1 inhibitor
+Has previously progressed on a PD-1 or PD-L1 checkpoint inhibitor for systemic disease
+Documented progression of disease after initiation of therapy with OR lack of response to therapy with a PD-1- or PD-L1-targeting monoclonal antibody (pembrolizumab, nivolumab, etc) after at least 18 weeks; NOTE: This treatment could have been at any time prior to registration
+No history of prior treatment with inhibitor of PD-1 or PD-L1 or PDL2
+Prior systemic therapy directed at MIBC – prior systemic therapy directed at non-muscle invasive disease (i.e. superficial bladder cancer [T1]) is permitted provided treatments within this study’s exclusion criteria were not used (cisplatin, anti-PD1) / anti-PD-L1 antibodies, etc.)
+Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies for their metastatic disease
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4 inhibitor including tremelimumab
+Previous treatment with PD-1 or PD-L1 directed therapy
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Patients must have analysis of PD-L1 expression in cancer cells quantitated by immunohistochemistry analysis
+Patients in Cohort 2 (high PD-L1) must have >= 50% expression
+Patients in Cohort 3 (low PD-L1) must have 0-49% expression
+Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy\r\n* Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression
+Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
+For patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy
+Determination by the treating medical oncologist that the patient is a candidate to continue the PD-1 or PD-L1 inhibiting therapy that the patient was receiving at the time of the most recent progression
+Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment\r\n* Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible
+Any prior PD-1/PD-L1 therapy-related adverse events (AE) that, in the opinion of the investigator, warrants exclusion from participation in this trial
+Any previous treatment with a PD-1 or PD-L1 inhibitor, including but not limited to: nivolumab, atezolizumab, pembrolizumab, or durvalumab
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Participant must have histologically confirmed hepatocellular cancer (HCC) that is advanced or metastatic and have archival tissue available for PD-L1, PD-L2 testing (NOTE: if participant has had prior radiotherapy to the liver, a mandatory fresh biopsy will need to be obtained since radiotherapy could affect PD-1/PD-L1 immune status)
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
+Receipt of the last dose of anti-cancer therapy (immunotherapy, endocrine therapy [e.g., abiraterone acetate, enzalutamide], targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug. (with the exception of any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.)
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Prior therapies for extracranial metastatic melanoma including chemotherapy, BRAFi/MEKi, cytokine or vaccine therapy as long as it did not include PD-1/PD-L1
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Prior exposure to any immuno-oncology agents, including CD40/PD-1/PD-L1/CTLA-4 inhibitors (if any ambiguity, should be discussed with study principal investigator)
+Most recent prior regimen was a PD-1 inhibitor (nivolumab or pembrolizumab) with progression; last dose must have been delivered within 90 days of enrollment
+Participants previously treated with BRAF inhibitors (vemurafenib, dabrafenib, encorafenib), MEK inhibitors (selumetinib, trametinib, binimetinib, cobimetinib), and/or anti-PD1/PDL1 monoclonal antibodies for metastatic or unresectable disease; any other prior therapy will be allowed (including ipilimumab, adjuvant anti-PD1 therapy, high-dose IL-2)
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, and therapeutic anticancer vaccine
+Previous treatment with Anti-CTLA-4 including tremelimumab or PD1/PD-L1 inhibitor, including durvalumab
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
+Patients must have received platinum-based therapy with or without bevacizumab, but may not have received a PD-1, PD-L1 or PD-L2 inhibitor
+Patients who have received previous immunotherapy with PD1 or CTLA4 antibodies are not eligible
+Must have progression of disease within 6 months of study enrollment after treatment with only one of the following:\r\n* Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or\r\n* One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, or
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
+Subjects must have progressed on or after previous platinum-based chemotherapy; subjects must have also progressed on or after receiving any single-agent PD-1 or PD-L1 inhibitor (including pembrolizumab) as their most recent therapy and must have had at least a 3-month PFS on this therapy
+Subjects must be enrolled on the trial within 6 weeks of their last infusion of PD-1 or PD-L1 inhibitor therapy
+Treatment with any investigational agent within 28 days prior to registration for protocol therapy with the exception of PD-1 or PD-L1 inhibitors
+History of an immune-related toxicity requiring treatment with corticosteroids during prior PD-1/ PD-L1 inhibitor treatment
+ADDITIONAL INCLUSION CRITERION FOR COHORT 1 (PD-1/PD-L1 INHIBITOR-NAIVE, CETUXIMAB-NAIVE) AND COHORT 2 (PD-1/PD-L1 INHIBITOR-REFRACTORY, CETUXIMAB-NAIVE):
+ADDITIONAL INCLUSION CRITERION FOR COHORTS 2 AND 3 (PD-1/PD-L1 INHIBITOR-REFRACTORY):
+PD-1/PD-L1 inhibitor-refractory patients must have documented disease progression after prior response to anti-PD-1/PD-L1 therapy (response defined as stable disease, partial or complete response)
+ADDITIONAL EXCLUSION CRITERION FOR COHORTS 1 (PD-1/PD-L1 INHIBITOR-NAIVE, CETUXIMAB-NAIVE) AND 4 (CUTANEOUS):
+Patient has received any prior immunotherapy with inhibitors of PD-1 or PD-L1
+Prior treatment of PD-1 or PD-L1-directed immune checkpoint blockade is permitted if treatment was not discontinued due to disease progression or life-threatening adverse events per the investigators’ discretion (laboratory abnormalities alone with prior therapy will not exclude patients from this trial)
+Acceptable marrow function and hematologic indices for PD1/PDL1 immune checkpoint inhibitor and nelfinavir as per standard of care
+Allergy or intolerance to nelfinavir or selected PD1/PDL1 immune checkpoint inhibitor
+Patients may have received any number and type of prior treatment regimens for their NSCLC (aside from patients in arm A, who cannot have had PD-1/PD-L1 inhibitors)
+Arm A: patients must be treatment naive to single agent PD-1/PD-L1 inhibitors including but not limited to durvalumab, pembrolizumab, atezolizumab, nivolumab, and avelumab\r\n* Arm B: patients’ tumor must be either refractory to or progressed on one of the above agents\r\nNOTE: Patients must be eligible to receive the next line of therapy and not be suspected of having pseudoprogression\r\n* Both cases are defined by initial progressive disease (PD) or PD after CR, PR, or SD using RECIST criteria, respectively
+Patients should not have received prior immunotherapies (exception; arm B); they include but are not limited to interleukin-2 and other immune checkpoint antagonist targeting CTLA-4, LAG-3, TIM-3, KIR etc. and/or agonists targeting OX40, ICOS, CD137, etc\r\n* NOTE: prior cancer vaccine treatments are permitted; for arm B, exposure to single agent PD-1/PD-L1 inhibitors are allowed >= 14 days from registration
+Arm B: patients must not have had prior exposure to combination treatment with PD-1/PD-L1 inhibitors and another systemic treatment\r\n* NOTE: radiation therapy and surgery do not count as combination treatment
+Patients who are intolerant to PD-1/PD-L1 inhibitors and/or metformin are excluded
+Any previous treatment with adoptive T cells therapy, a PD1 or PDL1 inhibitor, including durvalumab or any anti-CTLA4 therapy, including tremelimumab.
+No treatment with prior sipuleucel-T, PD-1 inhibitor, MPDL3280A or any other PD-L1 inhibitor, taxane-based chemotherapy for metastatic disease
+Prior treatment with ibrutinib or an anti-PD-1, or PD-L1 or PD-L2 agent or ipilimumab in the metastatic setting
+Progressive disease (PD) as best response to first-line therapy
+Inclusion Criteria Part 1 (CMP-001 + pembrolizumab):\n\n          1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant\n             melanoma. Ocular melanoma subjects are not eligible.\n\n          2. Male and female subjects age 18 or older\n\n        3a. Subjects who are currently receiving treatment with any anti-PD-1/PD-L1 antibody,\n        either alone or in combination and who are progressing. Subjects must have received at\n        least 4 doses of anti-PD-1/PD-L1 before enrolling into the CMP-001-001 study.\n\n        OR\n\n        3b. Subjects who have previously received any anti-PD-1/PD-L1 therapy, alone or in\n        combination and progressed, regardless of the best overall response to prior\n        anti-PD-1/PD-L1 based therapy. Subjects must have received at least 4 doses of\n        anti-PD-1/PD-L1.\n\n        4. Subjects must have at least one tumor lesion with a longest diameter of ?0.5 cm that can\n        be easily palpated or detected by ultrasound to facilitate intratumoral injection of\n        CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph node).\n\n        5. Subjects must have measurable disease by RECIST Version 1.1. 6. Capable of understanding\n        and complying with protocol requirements. 7. A life expectancy of greater than 24 weeks at\n        Screening. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 9.\n        Most recent laboratory values (within 3 weeks prior to Week 1 Day 1 (W1D1)) before study\n        entry meet the following standards:\n\n          -  Bone marrow function: neutrophil count ?1,000/mm3, platelet count ? 75,000/mm3 and\n             hemoglobin concentration > 8.0 g/dL.\n\n          -  Liver function: total bilirubin ? 1.5 times the upper limit of normal (ULN) ranges of\n             each institution, with the following exception: patients with Gilbert Disease serum\n             bilirubin > 3X ULN AND aspartate aminotransferase (AST) and alanine aminotransferase\n             (ALT) ? 3 times the ULN range of each institution.\n\n          -  LDH ?2.0 times the ULN range of each institution\n\n          -  Renal function: serum creatinine ? 1.5 times the ULN range of each institution. 10.\n             The subject must sign a written informed consent form prior to the initiation of any\n             study procedures. Adult subjects unable to provide written informed consent on their\n             own behalf will not be eligible for the study.\n\n        Part 1 Dose Expansion Phase subjects must also meet the following inclusion criterion:\n\n        11. At least one additional lesion that is measurable and is not intended for injection (to\n        allow an assessment of systemic antitumor effect). These lesions not intended for injection\n        may be located in any metastatic site.\n\n        Exclusion Criteria Part 1 (CMP-001 + pembrolizumab):\n\n          1. Pregnant or breastfeeding.\n\n          2. Received investigational therapy (e.g. small molecule or biologic) within 30 days\n             prior to the start of CMP-001 dosing on W1D1. However, if an investigational therapy\n             has a short half-life, a reduced wash out period may be acceptable with Sponsor\n             approval.\n\n          3. Received treatment with anti-CTLA-4 antibody within 30 days prior to the start of\n             CMP-001 dosing on W1D1.\n\n          4. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or\n             hepatitis C virus (HCV). If there is no known or documented history of HIV, Hepatitis\n             B or Hepatitis C, the site is not required to do additional testing for these values\n             at Screening.\n\n          5. Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Subjects who\n             developed autoimmune disorders of Grade ? 3 may enroll if the disorder has resolved to\n             Grade ? 1 and the subject has been off systemic steroids at doses > 10mg/day for at\n             least two weeks.\n\n          6. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of\n             10 mg/day; replacement doses, topical, ophthalmologic and inhalational steroids are\n             permitted. Subjects who have a history of adrenal insufficiency and are receiving\n             greater than 10 mg/day coticosteroid may be eligible but only after Sponsor\n             consultation. Subjects who are currently receiving steroids at a dose of ?10 mg/day do\n             not need to discontinue steroids prior to enrollment.\n\n          7. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. However\n             subjects with active CNS metastases are eligible for the trial if\n\n               -  the metastases have been treated by surgery and/or radiotherapy,\n\n               -  the subject is off corticosteroids > 10 mg/day and is neurologically stable for\n                  at least 2 weeks prior to Screening.\n\n               -  brain MRI completed within 3 months of screening (required for all subjects).\n\n          8. Any concurrent uncontrolled illness, including mental illness or substance abuse,\n             which in the opinion of the Investigator, would make the subject unable to cooperate\n             or participate in the trial.\n\n          9. Severe uncontrolled cardiac disease within 6 months of Screening, including but not\n             limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or\n             cerebrovascular accident (CVA).\n\n         10. Requires prohibited treatment (i.e., non-protocol specified anticancer\n             pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant\n             tumor).\n\n         11. Women of child-bearing potential who are unable or unwilling to use an acceptable\n             method of contraception.\n\n        Inclusion Criteria - Part 2: CMP-001 Monotherapy\n\n        Subjects must meet all of the following inclusion criteria to be eligible:\n\n          1. Histopathologically confirmed diagnosis of metastatic, or unresectable, malignant\n             melanoma. Ocular melanoma subjects are not eligible.\n\n          2. Male or female subjects age 18 or older.\n\n          3. Previously received any anti-PD-1/PD-L1 therapy, alone or in combination. Subjects\n             must have received a minimum of 4 doses of anti-PD-1/PD-L1 therapy prior to study\n             entry.\n\n          4. Subjects must have at least one tumor lesion with a longest diameter of ?0.5 cm that\n             can be easily palpated or detected by ultrasound to facilitate intratumoral injection\n             of CMP-001 (i.e., tumor in skin, muscle, subcutaneous tissue or accessible lymph\n             node).\n\n          5. Subjects must have measurable disease by RECIST Version 1.1.\n\n          6. Capable of understanding and complying with protocol requirements.\n\n          7. A life expectancy of greater than 24 weeks at Screening.\n\n          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to\n\n          9. Most recent laboratory values (within 3 weeks prior to first CMP-001 injection at Week\n             1 Day 1 (W1D1)) before study entry meet the following standards:\n\n               -  Bone marrow function: neutrophil count ?1,000/mm3, platelet count ?75,000/mm3 and\n                  hemoglobin concentration > 8.0 g/dL.\n\n               -  Liver function: total bilirubin ? 1.5 times the upper limit of normal (ULN)\n                  ranges of each institution, aspartate aminotransferase and alanine\n                  aminotransferase ? 3 times the ULN range of each institution.\n\n               -  LDH ?2.0 times the ULN range of each institution.\n\n               -  Renal function: serum creatinine ?1.5 times the ULN range of each institution.\n\n         10. The subject must sign a written informed consent form prior to the initiation of any\n             study procedures. Adult subjects unable to provide written informed consent on their\n             own behalf will not be eligible for the study.\n\n        Exclusion Criteria Part 2: (CMP-001 Monotherapy)\n\n          1. Pregnant or breastfeeding.\n\n          2. Received investigational therapy (e.g. small molecule or biologic) within 30 days\n             prior to the start of CMP-001 dosing on W1D1. Received prior therapy with an\n             anti-PD1/PD-L1 or anti-CTLA-4 within 45 days prior to the start of CMP-001 dosing on\n             W1D1. However, if an investigational therapy has a short half-life, a reduced wash out\n             period may be acceptable with Sponsor approval.\n\n          3. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or\n             hepatitis C virus (HCV). If there is no known or documented history of HIV, Hepatitis\n             B or Hepatitis C, the site is not required to do additional testing for these values\n             at Screening.\n\n          4. Subjects who developed autoimmune disorders of Grade ? 3 may enroll if the disorder\n             has resolved to Grade ?1 and the subject has been off systemic steroids at doses >10\n             mg/day for at least 2 weeks.\n\n          5. Require systemic pharmacologic doses of corticosteroids greater than the equivalent of\n             10 mg/d; replacement doses, topical, ophthalmologic and inhalational steroids are\n             permitted. Subjects who have a history of adrenal insufficiency and are receiving\n             greater than 10 mg/day of corticosteroid may be eligible but only after Sponsor\n             consultation. Subjects who are currently receiving steroids at a dose of ? 10 mg/day\n             do not need to discontinue steroids prior to enrollment.\n\n          6. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.\n             However, subjects with active CNS metastases are eligible for the trial if:\n\n               -  the metastases have been treated by surgery and/or radiotherapy.\n\n               -  the subject is off corticosteroids >10 mg/day and is neurologically stable for at\n                  least 2 weeks prior to Screening.\n\n               -  brain MRI completed within 3 months of screening (required for all subjects).\n\n          7. Any concurrent uncontrolled illness, including mental illness or substance abuse,\n             which in the opinion of the Investigator, would make the subject unable to cooperate\n             or participate in the trial.\n\n          8. Severe uncontrolled cardiac disease within 6 months of Screening, including but not\n             limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or\n             cerebrovascular accident (CVA).\n\n          9. Requires prohibited treatment (i.e., non-protocol specified anticancer\n             pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant\n             tumor).\n\n         10. Women of childbearing potential who are unable or unwilling to use an acceptable\n             method of contraception.
+Dose escalation cohorts: Patients with histologically or cytologically confirmed diagnosis of malignancy (including lymphoma) with demonstrated progression of a tumor for whom there is no available therapy likely to convey clinical benefit AND who have not been previously treated with a PD-1/PD-L1 inhibitor. These patients do not require measurable disease
+Dose expansion cohorts: Patients with histologically or cytologically confirmed diagnosis of 1 of specified tumors with measurable disease per RECIST 1.1 or Lugano criteria. Some patients may have been previously treated with a PD-1 or PD-L1 inhibitor
+Prior treatment with an agent that blocks the PD-1/PD-L1pathway
+Prior exposure to PD-1 or PD-L1 inhibitors is not allowed
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
+Any prior severe adverse event attributed to prior anti-PD1 therapy that, in the Principal investigator's opinion, would contraindicate pembrolizumab administration such as:
+Participant must have an advanced solid tumor and must not be a candidate for surgical resection or other approved therapeutic regimen known to provide clinical benefit. For dose escalation, the participant may have been previously treated with a programmed cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be PD-I/PD-L1 targeting agent naïve. For Combination, the participant must be have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve.
+Prior anti-PD-1/PD-L1 targeted therapy is NOT allowed; prior CTLA-4 therapy or CD40/CD40L targeted therapy is allowed
+Patients who have previously been treated with avelumab (or another PD1/PDL1 inhibitor) in combination with 5-azacytidine will be excluded
+History of discontinuation of any previous treatment with PARP inhibitors, including olaparib, or a PD-1 or PD-L1 inhibitor, including durvalumab or anti-CTLA4 antibody, including tremelimumab due to toxicity
+Has received prior immunotherapy with agents that target PD-1, PD-L1, PD-L2, CTLA-4, OX-40, or CD-137 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Have a PD-L1 positive (either strongly or weakly) tumor as determined by the IHC 22C3 pharmDx test at the study site; if a patient’s initial tumor specimen is not classified as PD-L1 positive by the central laboratory, a newly obtained specimen (different from the sample previously submitted) may be submitted for testing; if the newer specimen is classified as PD-L1 positive by the study site, the patient meets this eligibility criterion
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Prior treatment with nivolumab or any other PD1/PDL1 checkpoint inhibitor
+Prior treatment for CLL with CTLA-4, PD-1, PD-L1, or CD137 monoclonal antibody (mAb)
+Patients must not have had prior treatment with nivolumab or any other PDL1 or PD-1 antagonists
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+For Phase 1b LY3300054 monotherapy or combination therapy, no prior treatment with a PD-1 or PD-L1 agent is allowed.
+Prior chemotherapy or other systemic anticancer therapy within 4 weeks prior to start of olaparib treatment, 6 weeks for nitrosoureas or mitomycin. Exceptions include: Anti-hormonal treatment for ER positive or PR positive breast cancer is allowed until 7 days prior to treatment with olaparib, exposure to an investigational agent within 30 days or 5 half-lives (whichever is the longer) prior to start of olaparib treatment is not allowed, prior receipt of biologics targeting T cell co-regulatory proteins and/or immune checkpoints is not allowed. Examples include MEDI4736 or other PD1 or PD-L1 or PD-L2 inhibitors or anti-CTLA4 therapy, previous treatment with a PARP inhibitor, is not allowed.
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), including tremelimumab
+Has had prior treatment with any other anti-PD-1 or PD-L1 or PD-L2 agent
+Patients who have had prior systemic therapy with a PD-1 blocking antibody will be excluded
+Patients enrolled on the phase II randomized trial, who have had prior treatment with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway (i.e. not “immune therapy naive”)\r\n* Note: for those enrolled in the phase I dose escalation, prior use of a PD1 or PDL1, anti-CTLA4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway is allowed; for those enrolled in the phase IB, prior use of a PD1 or PDL1, anti-CTLA4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway is required; for all patients in all phases, prior use of a vaccine for treatment of cancer is allowed
+Patients enrolled in the phase Ib expansion who have never previously been treated with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway in the past (i.e. not \pre-treated”)
+Grade 3 or 4 major organ immune-related adverse events (IRAEs) following treatment with anti PD-1/PD-L1
+Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.
+Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
+Prior treatment with specific pathway-blockers (PD-1/PD-L1)
+Inclusion Criteria:\n\n        Adult male or female subjects with pathologically confirmed MDS who failed to respond,\n        relapsed after an initial response, or were unable to tolerate hypomethylating agents, ECOG\n        performance status of 0 - 2, and adequate organ and marrow function.\n\n        Exclusion Criteria:\n\n        Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment,\n        prior MAb against CTLA-4, PD-1, or PD-L1, alllogenic or haploidentical transplant, current\n        immunosuppressive medication or autoimmune or inflammatory disease.
+PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients who have had prior immune checkpoint inhibitors, such as MEDI4736 or other PD1 or PD-L1 inhibitors or an anti-CTLA4 therapy
+PHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nPatients who have had prior immune checkpoint inhibitors, such as MEDI4736 or other PD1 or PD-L1 inhibitors or an anti-CTLA4 therapy
+Prior treatment with immune checkpoint inhibitor, including (but not limited to) those targeting PD-1, PD-L1, PD-L2, CTLA-4, CD137, GITR, TIM3, LAG3, or OX40
+Patients who have been treated with prior PD-1 and PD-L1 agents
+TREATMENT: Patients should have been off conventional therapy for at least 1 week prior to entry in this study (except for lenalidomide, thalidomide, pomalidomide or immune checkpoint inhibitors such as CTLA4 and/or PD-1/PD-L1 inhibitors)
+Consent to baseline metastatic and progressive disease biopsy (of metastatic/progressing lesion) for enabling biomarker assessment and treatment assignment (at each time point – baseline, PD1, PD2, PD3) as well as for correlative studies\r\n* Consent to baseline and serial blood draws for plasma/serum/whole blood banking for correlative studies
+Patients can be either ipilimumab naïve or refractory to ipilimumab, defined as received at least two doses of ipilimumab and documented disease progression; patients who were re-treated with ipilimumab and patients who were on maintenance ipilimumab will be allowed to enter the trial as long as there is documented progressive disease (PD); progressive disease will be defined as increase in tumor burden > 25% relative to nadir (minimum recorded tumor burden) which is confirmed by repeat assessment no less than four weeks from the date of the first documented PD; once PD is confirmed, initial date of PD documentation will be considered as the date of disease progression; prior ipilimumab therapy must have been completed at least 12 weeks before study drug administration
+Patient had prior treatment with any other anti-PD-1, or PD-ligand (L1) or PD-L2 agent
+Progressive disease (PD)
+Any number of previous treatments with the exception of previous inhibitors of programmed cell death 1 (PD-1), PD-L1, or programmed cell death 1 ligand 2 (PD-L2); other prior systemic therapies must have been administered at least 2 weeks before administration of MK-3475 with the exception of bevacizumab which must have been administered at least 4 weeks prior to MK-3475; patients are not required to have had prior systemic therapy; the exception to this is patients with NSCLC who test negative for PD-L1 expression or are unevaluable for PD-L1 expression must have received prior platinum-based chemotherapy for entry into cohort 2\r\n* Note: ipilimumab treatment should have been administered at least 4 weeks prior to the start of MK-3475
+PD-L1 expression in tumor tissue from any site is required for patients with NSCLC for entry into cohort 1; tumor tissue must be obtained after the last systemic therapy; PD-L1 expression will be analyzed by a Merck assay; for NSCLC cohort 2, patients may test PD-L1 negative or may be unevaluable for PD-L1 expression (i.e. insufficient tumor tissue); PD-L1 expression is not required for patients with melanoma, but melanoma patients are required to submit an extra-cerebral specimen for analysis, unless it is not feasible to obtain one
+Has had prior treatment with any other anti-PD-1 or PD-L1 or PD-L2 agent or an antibody targeting other immune-regulatory receptors or mechanisms; examples of such antibodies include (but are not limited to) antibodies against indoleamine 2, 3-dioxygenase (IDO), PD-L1, interleukin-2 receptor (IL-2R), glucocorticoid-induced TNFR family related gene (GITR); prior ipilimumab, interleukin-2 (IL2), bevacizumab and adoptive cell therapy is allowed
+Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.
+Part 1b: Must have documented confirmed disease progression on a prior programmed cell death-1 (PD-1) pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.
+Phase II PD-1/PD-L1 refractory subsets: Patients with confirmed disease progression within 1 year following initiation of PD-1/PD-L1 inhibitor therapy (patients must have received at least 2 doses of the PD-1/PD-L1 inhibitor). No prior cytotoxic therapy in the advanced setting is permitted. BRAF inhibition therapy is acceptable before immunotherapy where clinically indicated. CTLA-4-inhibition therapy is acceptable as a prior line of therapy or in combination with anti-PD-1 therapy.
+Prior history of or active interstitial lung disease or pneumonitis, encephalitis, seizures, severe immune related adverse events with prior PD-1/PD-L1 containing treatments;
+Received prior therapies targeting PD-1 or PD-L1
+Newly diagnosed, metastatic NSCLC with a PD-L1 TPS ? 50% (as determined by central lab using the PD-L1 IHC 22C3 pharmDx kit) NOTE: Subjects with documentation of PD-L1 TPS ? 50% by IHC analysis using the 22C3 pharmDx kit will not require repeat PD-L1 testing by central laboratory; and
+Subjects with progression on or after first-line platinum-based chemotherapy who have a PD-L1 TPS ? 1% (as determined by central laboratory using the PD-L1 IHC 22C2 pharmDx kit). Subjects with EGFR or ALK genomic tumor aberrations with progression on FDA-approved therapy for these aberrations are eligible NOTE: Subjects with documentation of PD-L1 TPS ? 1% by IHC analysis using the 22C3 pharmDx kit will not require repeat PD-L1 testing by central laboratory;
+Patients who discontinued prior anti-PD-1/PD-L1 therapy due to an anti-PD-1/PD-L1-related toxicity.
+Prior chemotherapy, immunotherapy, radiotherapy or major surgery (including radiation therapy or surgery for treatment of brain metastases) must be completed at least 3 weeks before study entry; prior PD-1 or PD-L1 therapy is acceptable
+Patients whose tumors have PD-L1 expression in >= 50% of tumor cells must have demonstrated progression on or intolerance to pembrolizumab; otherwise, patients who are eligible to receive an FDA-approved anti-PD-1/anti-PD-L1 agent as second-line therapy must also have demonstrated progression on or intolerance to the drug
+PD on first-line therapy.
+Previous therapy with any PD1 or PD-L1 inhibitor (including durvalumab) for any malignancy.
+Either known PD-L1 expression at the time of treatment (measured using any FDA approved test) or PD-L1 expression demonstrated using the Ventana SP142 assay in a biopsy taken prior to the start of treatment
+Part 2: Has received prior therapy with cancer vaccines, or compounds targeting PD-1 (including Merck pembrolizumab [MK-3475]), PD-L1, PD-L2, CTLA-4, lymphocyte-activation gene 3 (LAG-3), CD-137, OX-40 (tumor necrosis factor receptor superfamily, member 4 [TNFRSF4], also known as CD134), cluster of differentiation 40 (CD-40), glucocorticoid-induced TNFR-related protein (GITR), serine/threonine-protein kinase B-Raf (BRAF), MEK or other molecules in the MAPK pathway.
+Has received prior treatment with PD-616 or low-dose cytarabine.
+With the exception of CRPC and mBC patients, patients should have received prior PD-1 / PD-L1-containing checkpoint inhibitor therapy administered as their most recent therapy and have failed to achieve a PR or CR within four (4) months of starting that therapy;
+PD-1 / PD-L1 checkpoint inhibitor therapy is permitted;
+Approved PD-1/PD-L1 inhibitors, CTLA4 checkpoint inhibitors, or other immunotherapy ? 4 weeks
+Experienced PD during participation in another Valor study
+Part 1: have a diagnosis of metastatic melanoma and be scheduled to receive anti PD1 immunotherapy
+Enrolled patients may be candidates for standard of care therapy with trabectedin or second line/subsequent line treatment for advanced disease with PD-1/PD-L1 inhibitor monotherapy; otherwise they should have no standard of care option available or be felt appropriate for a phase I clinical trial in the opinion of the treating investigator; prior PD-1/PD-L1 exposure is not an exclusion criteria
+Prior treatment with an agent that blocks PD-1/PD-L1 pathway or other immune modulating agents within fewer than 4 weeks of 4 half-lives
+Prior treatment with an anti-CTLA-4, including tremelimumab PD-1 or PD-L1 inhibitor, including durvalumab
+History of hypersensitivity to durvalumab or tremelimumab or any CTLA4, PD1, or PDL-1 inhibitor
+Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab, nivolumab or other CTLA-4, PD-1 or PD-L1 inhibitors
+Patients are excluded if they have a history of prior treatment with ipilimumab, CTLA-4 inhibitor or agonist, nivolumab, PD-1 or PD-L1 inhibitor
+Prior therapy with anti-PD-1, PD-L1, or PD-L2 agent.
+Prior PD-1- or PD-L1-directed therapy.
+Previous treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)
+Has received study therapy (including investigational device) as part of a clinical trial within 4 weeks of the first dose of treatment, with the exclusion of an anti-PD1/L1 antibody given as either a single agent or non-CTLA-4 antibody containing combination
+Patients are not eligible who have received prior immunotherapy including interleukin-2 and immune checkpoint antagonists and/or agonists (including but not limited to PD-1, PD-L1, CD137, or OX40)\r\n* NOTE: Single agent anti-CTLA4 monoclonal antibody treatments are permitted; cancer vaccine therapies are permitted
+Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the metastatic setting
+Patients must have received or be ineligible for platinum based chemotherapy and must have received at least one line of therapy with a PD-L1 or PD-1 targeting agent
+DOSE ESCALATION COHORT: Subjects who have received an IDO inhibitor; subjects who have received other immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, and any other treatment targeting T-cell) will be permitted; subjects who have received experimental vaccines or other immune therapies should be discussed with the principal investigator (PI) to confirm eligibility
+DOSE EXPANSION COHORT: Subjects who have received an IDO inhibitor; subjects who have received other immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, and any other treatment targeting T-cell) will be permitted; subjects who have received experimental vaccines or other immune therapies should be discussed with the PI to confirm eligibility
+Tumor sample must be available for HPV p16 and PD-L1 testing
+Subjects must have had clinical benefit while on a PD-1 or PD-L1 inhibitor defined as at least a 3 month PFS, and now have disease progression.
+Most recent PD-1 or PD-L1 inhibitor infusion must be completed at least 6 weeks of randomization. The subject must have recovered from all reversible acute toxic effects (other than alopecia) to =< grade 1 or baseline.
+Previous discontinuation from PD-1 or PD-L1 due to an adverse event.
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Patient with strong PD-L1 expression (>= 50% of tumor cells expressing PD-L1 ot or tu or TPS >= 50% ) will be excluded; patient’s with unknown PD-L1 expression or when PD-L1 expression can’t be determine
+Have provided tissue from an archival or newly obtained tissue sample of a tumor lesion, sufficient for analysis of programmed cell death 1 ligand 1 (PD-L1) and other biomarkers; patients who have had PD-L1 analysis previously performed at Merck can substitute earlier analysis results and are not required to submit additional tissue for PD-L1 testing; expression of PD-L1 is NOT required for study entry
+Prior treatment with a PD-1, PD-L1, or PD-L2 blocking therapy
+Patients must be candidates for PD-L1 antibody (Ab) as determined by the treating physician
+Patients must not be on any other systemic therapy within the following intervals before study enrollment:\r\n* 1 week after stereotactic radiosurgery of the brain or comparable technology\r\n* 4 weeks after cytotoxic chemotherapy or external beam radiation therapy\r\n* 6 weeks after chemotherapy regimens including BCNU (carmustine) or mitomycin C\r\n* Patients who experience melanoma progression (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) while on or after treatment with programmed cell death 1 (PD-1) or PD ligand-1 (PDL-1) antibody may enroll on this study\r\n** NOTE: Patients must be off PD-1/PDL- antibody for at least 2 weeks to assess for delayed toxicity before being enrolled and receiving INCB024360; patients who are enrolled 2 weeks and up to 6 weeks after the last dose of PD-/PDL-1 antibody will enroll in cohort B and receive 100 mg BID of INCB024360; patients enrolled beyond the 6 week period after failing anti-PD-1/PDL-1 will be enrolled in cohort A; cohort A patients will receive 300 mg BID of INCB024360; patients must not have active grade 2 autoimmune toxicities attributed to these antibodies at study entry\r\n* 8 weeks after ipilimumab, other cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody or other immunologically active antibody\r\n** NOTE: Patients receiving prior CTLA-4, anti-PD1 antibody or other immunologic therapy must show evidence of normal pituitary function at baseline and must not have active grade 2 autoimmune toxicities attributed to these antibodies at study entry
+Ipilimumab or other immunologically active therapy within 8 weeks of enrollment; NOTE: patients who experience melanoma progression (by RECIST 1.1 criteria) while on or after treatment with PD-1 or PDL-1 antibody may enroll on this study
+Current or history of systemic autoimmune disease requiring systemic therapy, including significant autoimmunity associated with prior ipilimumab therapy or therapy with antibodies to PD-1 or PD-L1
+Must not have known glucose-6-phosphate dehydrogenase (G-6PD) deficiency
+Subjects must have a tumor sample that is adequate for PD-L1 assessment prior to randomization.
+Subjects may not have been previously treated with talimogene laherparepvec, any other oncolytic virus, pembrolizumab, or any other inhibitor of PD-1, PD-L1, or PD-L2.
+Primary refractory melanoma: Subjects must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and have progressive disease as their best response to treatment that is confirmed 4 weeks later.
+Relapsed melanoma: Subjects must have received prior anti?PD-1 or anti?PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and achieved partial response ore complete response but later have confirmed progressive disease.
+Prior PD-1 or CTLA-4 targeted therapies are excluded
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Prior PD-1 or CTLA-4 targeted therapies are excluded.
+Must have achieved at least a minimal response (MR) to at least 1 prior anti-myeloma regimen before developing PD (relapsed)
+Unless unavailable, must have received at least one of cabozantinib or nivolumab (or other active anti-PD-1/PD-L1 therapy)
+Must have disease progression on a prior PD-1-pathway targeted agent.
+Must have had documented disease progression while on a prior PD-1 pathway-targeted agent.
+b. In Part 2SA, patients with an inadequate response to anti-PD-1 mAb therapy, defined as SD or PD using RECIST v1.1 criteria following at least 2 months of therapy. Patients with PD have a tumor measurement increase of < 2 fold from the time of starting anti-PD-1 therapy, must not have worsening of Eastern Cooperative Oncology Group (ECOG) performance status due to their disease progression, and cannot have new CNS lesion. Patients must also meet the lactic acid dehydrogenase (LDH) or ECOG status. No tumor size criteria are used in Part 2SA.
+If enrolled in Part 2SA, new, growing, or previously untreated lesions since the start of anti-PD-1 therapy.
+Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co-regulatory targets such as 4-1BB
+Patients are ineligible if they have a history of prior treatment with ipilimumab, bevacizumab, or prior tumor CD137 agonist or CTLA-4 inhibitor or agonist; patients may be treatment naive or have had one prior systemic therapy for metastatic disease as outlined in the eligibility criteria; patients may have received PD-1 or PD-L1 as per current protocol eligibility, although they are not currently commercially approved in the front line setting
+Prior therapy with pomalidomide with best response of PD or SD.
+Patients must have relapsed after having achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed PD.
+Participants without a PD-L1 test result are eligible for the study
+Subject who received any prior monoclonal antibodies against PD-1 or PD-L1 and/or any prior:
+For the expansion stage, evaluable for PD-L1 expression
+Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled
+Prior therapies targeting PD-1 or PD-L1.
+Subjects who fail to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
+Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
+No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease
+The patient may not have received treatment with immune checkpoint inhibitors (e.g., products that target PD-L1, PD-1, or CTLA-4).
+The patient must have received treatment with an immune checkpoint inhibitor or combination (e.g., products that target PD-1, PD-L1, or CTLA-4) or be intolerant to, or refuse such treatment.
+The patient may have received treatment with an immune checkpoint inhibitor (e.g., products that target PD-L1, PD-1, or CTLA-4).
+The patient may not have received treatment with an immune checkpoint inhibitor (e.g., products that target PD-L1, PD-1, or CTLA-4).
+The patient may have been treated with an immune checkpoint inhibitor (e.g., products that target PD-L1, PD-1, or CTLA-4).
+The patient may have been treated with an immune checkpoint inhibitor (e.g., products that target PD-L1, PD-1, or CTLA-4).
+The patient may not have received treatment with immune checkpoint inhibitors (e.g., products that target PD-L1, PD-1, or CTLA-4).
+Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.
+Intolerance to prior anti-PD-1/PD-L1 therapy
+Patients must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination.
+Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1, but excludes other experimental therapies). Patients must have received at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.
+Patients who have received prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 2 weeks prior to registration; hormone therapy is permitted until registration\r\n* Note: patients who received prior anti-PD-1, PD-L1 or PD-L2 agents are still eligible; a wash-out period of 2 weeks prior to registration is required
+Prior use of lenalidomide, or monoclonal antibodies against CTLA-4, PD-1, or PD-L1.
+Prior treatment with atezolizumab or another PD-L1/PD-1 therapy
+Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
+Has received one prior systemic therapy regimen for metastatic renal cell carcinoma (mRCC) directed against PD-1 and/or PD-L1 which must have been the most recent regimen\r\n* Prior high-dose interleukin-2 therapy is permitted in addition to anti-PD(L)1 therapy, but is not required\r\n* Prior bevacizumab or vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is permitted either in combination with anti-PD(L)1 therapy OR as monotherapy when given PRIOR to anti-PD(L)1 therapy\r\n* Prior treatment with combined ipilimumab and nivolumab is permitted\r\n* Prior axitinib in any setting is not permitted
+Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in a Merck pembrolizumab (MK-3475) study
+Particpant has received prior therapy with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanism, including participation in any other pembrolizumab trial and treatment with pembrolizumab. a. Examples of such antibodies include (but are not limited to) antibodies against indoleamine 2,3-dioxygenase (IDO), PD-L1, IL-2R, glucocorticoid-induced tumor necrosis factor receptor (GITR).
+Part B: Anti-PD-1 non-responders are defined as those showing disease progression according to RECIST v1.1 after at least 12 weeks of therapy with a PD-1 antibody either alone or in combination with approved checkpoint inhibitor or targeted therapies according to their label; there is no serological requirement
+Nonresponsive to most recent therapy (stable disease only or PD while on treatment), or
+For patients in the pazopanib hydrochloride (pazopanib) cohort, no prior systemic therapy for mRCC is allowed, with the exception of prior cytokine therapy (such as interleukin-2, IFN-a), immunotherapy (such as anti-PD-1 or anti-PD-L1), or supportive therapies (such as zoledronic acid, denosumab)
+ONLY FOR PART B – PD-L1 selection should a PD-L1 expression threshold have been defined in Part A and potentially additional mesothelioma trial data; there will be no PD-L1/biomarker selection for Part A
+Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled.
+Prior therapy with a PD-1, PD-L1, or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy
+Confirmed PD-L1-negative SCCHN by Ventana SP263;
+Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:
+PD-L1+ on immunohistochemistry testing performed by central lab
+Histological or cytological diagnosis of NSCLC. Patients must have 1) previously received prior anti-PD-L1 or anti-PD-1 mAb as most recent therapy, AND 2) did not have progressive disease as best overall response on recent PD-L1/PD-1 therapy (ie, stable disease 3 months, PR, or CR), AND 3) who subsequently progressed on anti-PD-L1 or anti-PD-1 mAb.
+Prior systemic therapy targeting PD-1: PD-L1 axis.
+Has received prior therapy with compounds targeting programmed death (PD)-1, PD-L1, PD-L2, or a mitogen-activated protein kinase (MAPK) pathway inhibitor
+Progressive Disease (PD) following standard chemoradiation
+Expansion Cohort 5: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (anti-PD1 or anti-PD-L1) as the most recent therapy for the treatment of inoperable, locally advanced, or metastatic disease.
+Expansion Cohort 7: Subjects with Stage IV non-squamous NSCLC who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) as the most recent therapy for metastatic disease.
+Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
+Any previous treatment with an anti-CTLA4, including tremelimumab or any previous treatment with a PD1 or PDL1 inhibitor
+Patients who have a diagnosis for which a PD-(L)-1 inhibitor has been approved must have previously received treatment with one of these therapies. a. Melanoma Dose Expansion: Patients must have histologically confirmed metastatic melanoma (ocular melanoma not included) which has progressed on or after treatment with a PD-(L)1 inhibitor.
+Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or any anti-CTLA4, including tremelimumab
+Have documented objective radiographic or clinical disease progression after PD-1/PD-L1 +/- anti-CTLA-4 inhibitor therapy (melanoma) or after at least 1 line of chemotherapy for metastatic disease (TNBC)
+Patients who have progressive disease (PD) but have experienced \clinical benefit\ as defined in the study protocol
+Has received prior therapy with PD-1, PD-L1, or CTLA-4 inhibitor
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
+Ten patients with a diagnosis of NSCLC who have disease progression per investigator's assessment who are on anti PD-1 or PD-L1 therapies will be allowed to enroll in the phase II part of this study but must be switched to treatment per this protocol
+Patients who have had chemotherapy or radiotherapy within14 days prior to entering the study; patients may not be currently receiving any other investigational agents or immunomodulatory agents (e.g. ipilimumab); patients treated with prior PD-1 or PD-L1 directed therapies are ineligible for the phase I portion
+Immunotherapy, such as interferon, interleukin-2, GM-CSF, ipilimumab, anti-PD1 or other experimental agent.
+For Part 1b: Must have documented confirmed disease progression on a prior PD-1 pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.
+Subjects who have received prior therapy with regimens containing CTLA-4, PD-L1, or PD-1 antagonists may be permitted to enroll under certain conditions
+Previously treated with a histone deacetylase inhibitor (i.e., vorinostat, belinostat, romidepsin, panobinostat), PD-1/PD-L1-blocking antibody (i.e., atezolizumab, nivolumab, pembrolizumab), or a cytotoxic T-lymphocyte associated protein-4 (CTLA-4) agent
+Prior therapy with single agent nivolumab, pembrolizumab or other PD-1/PD-L1 antibody or prior therapy with ipilimumab/CTLA-4 antibody for metastatic/unresectable disease is allowed unless they have received it as combination immunotherapy. Patients who received these agents in the adjuvant setting may be enrolled, provided it has been at least 3 months since receiving therapy
+Known glucose-6-phosphate dehydrogenase (G-6PD) deficiency
+Subject eligibility will be based on PD-L1 expression as determined by a specified IHC assay.
+A patient must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and later experienced disease progression, within 3 months of registration on this study
+All patients must have received at least one line of systemic therapy in the metastatic setting; prior immunotherapy is allowed, including prior treatment with nivolumab, another PD-1 inhibitor, or a PD-L1 inhibitor, as long as the reason for discontinuation of a prior PD-1 pathway inhibitor was not for drug-related toxicity
+Subject has received PD-1/PD-L1 blockade or has been informed of the results of relevant positive Phase 3 trials with these agents.
+Cohort 1 (combination of niraparib and PD-1 inhibitor): patients must have tumors with high PD-L1 expression (TPS ? 50%) per local assessment; with no known EGFR sensitizing mutation and/or ROS-1 or ALK translocations, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC
+Cohort 2 (combination of niraparib and PD-1 inhibitor): patients must have tumors with PD-L1 expression (TPS between 1% and 49%) per local assessment, with no known EGFR-sensitizing mutation and/or ROS-1 or ALK translocation, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC
+Cohort 3 (single agent niraparib): patients must have metastatic sqNSCLC and have progressed after both prior platinum-based chemotherapy and prior PD-1 or PD-L1 inhibitor treatment
+NSCLC Cohorts (CIT-Naïve): Participants with histologically confirmed incurable, advanced NSCLC not previously treated with anti-PD?L1/PD-1 and/or with anti-CTLA?4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD?L1/PD-1 antibody is considered an acceptable treatment option (if CIT [including anti-PD?L1/PD-1 agents] is approved as treatment for NSCLC by local regulatory authorities).
+NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable, advanced NSCLC previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
+Colorectal cancer (CRC) Cohort: Participants with histologically confirmed incurable, advanced adenocarcinoma of the colon or rectum not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
+Urothelial carcinoma (UC) Cohort (CIT-Naïve): Participants with histologically confirmed incurable, advanced transitional cell carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, and urethra, not previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD?L1 antibody is considered an acceptable treatment option, if CIT (including anti-PD?L1/PD-1 agents) is approved as treatment for UC by local regulatory authorities
+UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
+Melanoma Cohort: Participants with histologically confirmed incurable, advanced melanoma not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved) in the metastatic setting Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of Phase 1b:
+In the NSCLC CIT-Treated exploration cohort in Phase 1b, the most recent systemic treatment should have been anti-PD?L1/PD-1 and/or anti-CTLA-4 as monotherapy or in combination
+Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
+Prior treatment with systemic immune modulating agents (other than anti-PD-1/PD-L1 agents) that was within 28 days prior to enrollment, or within 90 days prior to enrollment if there was an immune related adverse event, or associated with toxicity that resulted in discontinuation of the immune modulating agent
+Completion of PD-L1 testing\r\n* Patients will be stratified as PD-L1 >= 5% versus (vs) < 5% OR inevaluable; baseline tumor will be utilized; if this returns inevaluable, efforts should be made to utilize the resected specimen
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Prior treatment with ibrutinib, a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor
+Has had treatment a prior monoclonal antibody targeting PD-1, PD-L1, PD-L2, or CTLA-4
+Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2 agent or participation in any MK-3475 Merck studies
+Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
+Patients must NOT have received any class of drugs targeted to the PD-1/PD-L1 pathway
+Key Inclusion Criteria\n\n        All Study Parts:\n\n          -  Diagnosis of cancer that has been histologically or cytologically confirmed\n\n          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1\n\n        Part A (1 of the following):\n\n          -  Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer,\n             bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or\n             gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST\n             v1.1 and meets 1 of the following criteria:\n\n               -  is refractory to standard of care\n\n               -  no standard therapy available\n\n               -  patient refuses standard therapy\n\n          -  Advanced, unresectable, or metastatic melanoma with or without prior treatment and\n             measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1\n\n          -  Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score [TPS] ?\n             50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 (1\n             of the following):\n\n               -  1) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic\n                  aberrations\n\n               -  2) Disease progression on or after platinum-containing chemotherapy;\n\n               -  3) If tumor has EGFR or ALK genomic aberrations, disease progression on an\n                  FDA-approved therapy for EGFR or ALK genomic tumor aberrations\n\n        Phase 2 (1 of the following):\n\n          -  Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an\n             anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy\n\n          -  Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with\n             measurable disease as defined by RECIST 1.1, that had progressed within 6 months of\n             completing ? 4 cycles of platinum-based therapy\n\n          -  Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with\n             measurable disease as defined by RECIST v1.1 in patients who have received at least\n             one prior line of systemic therapy for their disease\n\n        Key Exclusion Criteria\n\n          1. Prior treatment as follows:\n\n               -  Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4\n                  [CTLA-4] inhibitor).\n\n             NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was\n             administered as adjuvant therapy and treatment was completed at least 3 months prior\n             to enrollment.\n\n               -  Phase 2:\n\n                    -  A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.\n\n                    -  prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4\n                       inhibitor)\n\n          2. Symptomatic brain metastasis at screening\n\n          3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a\n             chronic medical condition that requires chronic steroid therapy or immunosuppressive\n             medication\n\n          4. History of pneumonitis or interstitial lung disease\n\n          5. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality\n             that may increase the risk associated with study participation or study drug\n             administration or that may interfere with the interpretation of study results and, in\n             the judgment of the Investigator, would make the patient an inappropriate candidate\n             for the study\n\n          6. Ocular melanoma
+Melanoma (anti-PD-1/PD-L1 therapy naïve or pre-treated)
+Non small cell lung cancer (anti-PD-1/PD-L1 therapy naïve or pre-treated)
+Renal Cell Carcinoma (anti-PD-1/PD-L1 therapy naïve or pre-treated)
+Prior participation in an interventional, investigational cancer vaccine or immunotherapy study except for an anti-PD-1/PD-L1 study.
+Patients with planned laparoscopic PD
+No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
+Previous treatment with rociletinib or MPDL3280A, or other 3rd generation EGFR TKI (eg, AZD-9291, HM61713), or PD 1 axis targeted therapy (eg, anti PD 1 or anti-PD L1)
+Having received any prior MAb (monoclonal antibodies) against CTLA-4 (cytotoxic T lymphocyte-associated antigen), PD-1, or PD-L1 or having received other investigational MAbs (monoclonalantibodies) within 6 months
+Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti- CTLA-4, including tremelimumab
+Prior use of systemic checkpoint inhibitors (including PD-1, PD-L1, and CTLA-4 targeting agents) for the management of ACC, non-urothelial bladder cancer/upper tract, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor is excluded
+Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks
+Prior treatment with anti PD-1 or PD-L1 therapy (Arm A)
+Patients treated with PD-1 or PD-L1 inhibitors, CDK 4/6 inhibitors, or other immune-based therapy are eligible
+Prior exposure to PD-1 or PD-LI treatment
+Has received prior treatment with PD-1/PD-L1 pathway inhibitors in the adjuvant setting
+Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by surgery as part CC# 14524, or planned to undergo treatment with anti-PD-1 or anti-PD-L1 per standard of care
+Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
+Previous exposure to CD40, PD-1, PD-L1, CTLA-4 antibodies or any other immunomodulatory agent
+Subjects who have previously received any anti-PD-1/PD-L1 therapy, alone or in combination. Subjects must have received at least 4 doses of anti-PD-1/PD-L1 therapy
+Group D only: Patients who have received only one prior systemic therapy treatment consisting of a PD-1 and/or PD-L1 inhibitor with or without a CTLA4 inhibitor for NSCLC, with exception of neo-adjuvant or adjuvant therapy as depicted in inclusion criterion 4. The last dose of prior immunotherapy must have been administered at least 6 weeks prior to the start of study treatment (cycle 1 day 1).
+Prior therapy with an agent that blocks the PD-1/PD-L1 pathway
+Prior therapy with talimogene laherparepvec, pembrolizumab, other anti-PD-1, any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathway.
+Progressive Disease (PD) during prior aromatase inhibitor (AI) therapy.
+No evidence of PD for ?3 months before the first dose of study drug.