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
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
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.
Subjects who have received prior anti-PD-1 or anti-PD-L1 antibody, or an IDO inhibitor; subjects who have received experimental vaccines or other immune therapies should be discussed with the principal investigator to confirm eligibility
Patients who have previously received an immune checkpoint inhibitor (e.g., anti- PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the checkpoint inhibitor resolved to ? Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous hypothyroidism toxicity on a checkpoint inhibitor are eligible to enter study regardless of Grade resolution as long as the patient is well controlled on thyroid replacement hormones.
Subjects who have received any prior cytotoxic therapy, immunotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks or 5 half-lives, whichever is shorter, prior to course 1, day 1 (C1D1) (6 weeks prior for checkpoint inhibitors such as anti-CTLA-4 or anti-PD1/PD-L1 and for nitrosoureas or mitomycin C); subjects must not have received radiotherapy in the 2 weeks prior to C1D1; subjects who had grade >= 3 immune-related adverse event (irAE) during previous treatment with one of the checkpoint inhibitors are excluded from the trial; subjects who had grade 1 or 2 irAE that have resolved to grade 1 are eligible
Has previously progressed on a PD-1 or PD-L1 checkpoint inhibitor for systemic disease
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 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
Prior treatment with nivolumab or any other PD1/PDL1 checkpoint inhibitor
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”)
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
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
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)
Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.
PD-1 / PD-L1 checkpoint inhibitor therapy is permitted;
Approved PD-1/PD-L1 inhibitors, CTLA4 checkpoint inhibitors, or other immunotherapy ? 4 weeks
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.)
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
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
Prior treatment-related toxicity resolved to =< grade 1 or baseline with the exception of alopecia and permanent grade =< 2 toxicities related to prior immune checkpoint inhibitor treatment (e.g. PD-1/PD-L1, CTLA-4, CD40, LAG3) treatment with the review and approval by the lead principal investigator (PI)
Subject has previously been treated with a HDAC inhibitor, PD-1 inhibitor, PD-L1 inhibitor, PD-L2 inhibitor, CTLA-4 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
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).
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.
Expansion Cohort 8: Subjects with Stage IV non-squamous NSCLC who have not received prior immune checkpoint inhibitor therapy (anti-PD-1 or anti-PD-L1).
Prior treatment with ibrutinib, a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor
Has not received prior therapy with CTLA-4, PD-1/PD-L1 inhibitors, other co-stimulatory or co-inhibitory immune checkpoint antibody therapies (e.g. LAG3, TIM3, CD137, KIR3DL, CD70, and CD27) for distant metastatic melanoma; patients who have received MAPK inhibitors are allowed on condition that they have recovered from adverse events to at most grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and at least 15 days have elapsed between last dose of MAPK inhibitors and C11-AMT imaging; patients who have previously received CTLA-4 inhibitors in the adjuvant setting are allowed to participate as long as they discontinued CTLA-4 treatment at least 30 days ago; patients who have previously received adjuvant PD- 1 inhibitors are excluded
Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of subjects who received atezolizumab in this study and are eligible for re-treatment
Patient has received prior therapy with an anti- programmed death receptor 1 (anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2) agent.
Patients must have had prior treatment with anti-PD1 or anti-PD-L1 agents and had documented disease progression either while on these agents or after stopping therapy with these agents without intervening therapy; patients must have discontinued anti-PD-1 or anti-PD-L1 therapy at least 21 days prior to registration
Patients must not have achieved a confirmed partial or complete response to the anti-PD-1 or anti-PD-L1 agents prior to progression
Patients must not have had systemic therapy, excluding anti-PD-1 or anti-PD-L1 agents, within 21 days prior to registration
Patients must not have had:\r\n* Prior treatment with ipilimumab or other CTLA-4 antagonists\r\n* Systemic therapy between progression on the anti-PD-1 or anti-PD-L1 agents and registration\r\n* Note: Systemic therapy (including BRAF-targeting agents) prior to anti-PD-1 or anti-PD-L1 therapy is allowed
Prior treatment with any PARP inhibitor or any anti-PD-1/anti-PD-L1 antibody
Prior treatment with lenvatinib or any PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding melanoma and NSCLC where prior treatment with one PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed
No prior therapy with a CDK 4/6 inhibitor; prior anti-PD-1 and anti-PD-L1 therapy is permitted
Received any systemic therapy for cancer treatment including immunotherapeutic agents such as anti-PD1 or anti-PD-L1 antibody therapy.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Subject has already received one of the following therapy/treatment: anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2, or HSP inhibitor
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; has been on any prior Merck MK-3475 (pembrolizumab) studies
Refractory to prior anti-PD-1/PD-L1 agent
The subject has received prior pembrolizumab or any other anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab
Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Intolerance to prior anti-PD-1/PD-L1 therapy
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; please contact the principal investigator for further clarification if needed
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 oranti-CTLA-4 antibody
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior anti-PD-1 or anti-PD-L1 therapy may not be administered after ACT and before study atezolizumab (MPDL3280A) administration
COHORT 1: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
COHORT 2: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior exposure to an anti-PD-1, anti-PD-L1 or anti-PD-L2
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (only cohort A)
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
Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor.
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent are not eligible
Prior anti-cancer treatments such as chemotherapy, radiotherapy, hormonal, or immunotherapy (including anti-PD-1/PD-L1) are permitted
Prior disease progression on anti-PD-1 therapy
Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent
Received prior therapy with an anti-CTLA-4, anti-PD-1, anti-PD1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent within 8 weeks prior to initiation of study treatment depending on study part
Prior treatment with anti-PD-1 or PD-L1 therapies
The participant has received prior pembrolizumab or any other anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent\r\n* This criterion does not apply to eligibility for second course treatment
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Prior therapy with anti-PD-L1 and anti-PD1 antibodies, MEK inhibitors or MDM2 antagonists.
Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
For Parts B and C, patients who received previous anti- PD-1, anti-PD-(L)1 treatment
Patients may not have received prior anti PD-1 or anti PD-L1 inhibitors
History of prior therapy with an IDO1 inhibitor in combination with an anti-PD-1/anti-PD-L1 agent/any other drug specifically targeting checkpoint pathways; patients who have received prior therapy with single agent anti-PD-1/anti-PD-L1 therapy or single agent IDO1 inhibitor will be eligible for this study
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR) (e.g., CTLA-4, OX 40, CD137).
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA4 or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Previous anti-PD1 or anti-PD-L1
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent within the prior 24 weeks
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 agent, or mifepristone
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Patients who received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent without having had evidence of objective response
Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1)
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior immunotherapy or treatment with another anti PD 1 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Previous therapy for this cancer with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or any other immunomodulatory agent
Has received prior anti-PD-1 or anti-PD-L1 therapy
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
Has received prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has had prior treatment with any other anti-PD-1 or PD-L1 or PD-L2 agent
Prior treatment with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior therapy with anti-PD1 antibody
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2
Patient had prior treatment with any other anti-PD-1, or PD-ligand (L1) or PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Patients who discontinued prior anti-PD-1/PD-L1 therapy due to an anti-PD-1/PD-L1-related toxicity.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or blinatumomab
REGISTRATION TO TREATMENT (STEP 1): Patient must not have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent for dose expansion; (patients in dose escalation may have received an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent)
Prior therapy with anti-PD-1, PD-L1, or PD-L2 agent.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or other immune checkpoint inhibitor (e.g. anti-CTLA4)
Prior treatment with an investigational compound being tested in this study (e.g., poly ADP ribose polymerase [PARP] inhibitor, anti-PD-1, anti-PD-L1, or anti-PD-L2)
Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the metastatic setting
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior immunotherapy including anti-programmed cell death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in Merck pembrolizumab (MK-3475) studies.
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD ligand 1 [anti-PD-L1], and anti-PD-L2
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in MK-3475 clinical trials.
Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137).
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
No prior treatment with anti-PD-1 or anti-PD-L1
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the subject has previously participated in Merck MK-3475 clinical trials.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
Has received prior immunotherapy including anti-programmed death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in clinical studies with pembrolizumab (MK-3475)
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
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in a Merck MK-3475 clinical trial.
Intolerance to prior anti-PD-1/PD-L1 therapy
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior treatment with anti-PD-1, PD-L1, or CTLA4, or ensartinib (X-396).
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or has participated in another Merck pembrolizumab clinical trial
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
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
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, OR other immune check point agonist/inhibitor.
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 monoclonal antibody.
Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously participated in Merck MK-3475 clinical trial
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
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 exposure to any anti-PD-1 or anti-PD-L1 antibody
Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5 and 7 in which prior anti-PD-1 or anti-PD-L1 therapy is required for eligibility. Other restrictions regarding prior therapy may apply.
Patients who received prior anti-PD-1 therapy are eligible for cohort 1 only and patients who have not received prior anti-PD-1 therapy are eligible for cohort 2 only
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
With TNBC has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Tumor for which standard therapy, including approved anti-PD-1 or anti-PD-L1 therapy, when applicable, does not exist or is no longer effective.
Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 therapy.
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
Must have received either nivolumab or pembrolizumab or a different IND-approved anti-PD1 or anti-PD-L1 therapy, unless medically contraindicated
Subjects who are treatment-naive or pretreated (prior anti-PD-1 or anti-PD-L1 required) in the recurrent/metastatic setting.
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
Patient must have had prior treatment with anti-PD-1 or anti-PD-L1 agents and have documented disease progression on these agents prior to registration; patient must have received anti-PD-1 or PD-L1 based therapy as the immediate previous line of treatment and within 56 days prior to registration
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Prior treatment with anti PD-1 or PD-L1 therapy (Arm A)
Prior systemic chemotherapy within 2 weeks of planed anti-PD1 treatment.
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Subjects who are currently receiving treatment with the anti-PD-1 antibody Pembrolizumab either alone or in combination and are progressing. Subjects must have received at least 4 doses of anti-PD-1/PD-L1 therapy OR
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
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
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
No prior treatment with any therapy on the PD-1/PD-L1 axis
Prior PD-1- or PD-L1-directed therapy.
Prior treatment with an agent that blocks the PD-1/PD-Ligand 1 pathway;
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.
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
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 treatment with a PD-1/PD-L1 inhibitor
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 a minimally invasive PD, such as laparoscopic or robotic PD
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
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
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
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
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
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
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.)
Previous treatment with PD-1 or PD-L1 directed therapy
Patients in Cohort 2 (high PD-L1) must have >= 50% expression
Patients in Cohort 3 (low PD-L1) must have 0-49% expression
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
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)
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
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)
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)
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
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)
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
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
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
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
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
Prior therapy with an anti-PD-1/PD-L1 antibody or a TRAIL-DR5 antibody
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
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
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
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.
Patients who have had prior systemic therapy with a PD-1 blocking antibody will be excluded
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.
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.
Patients who have had prior therapy (BRAF inhibitors, ipilimumab, anti PD-1 antibody or anti PD-L1 antibody) or treatment naive patients are eligible as long as toxicity from therapy is grade =< 1 or at baseline
Patients who have been treated with prior PD-1 and PD-L1 agents
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
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
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 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.
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;
Experienced PD during participation in another Valor study
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
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
Prior PD-1- or PD-L1-directed therapy.
Have experienced disease progression during treatment with an anti-PD1/L1 antibody as the treatment regimen immediately prior to accrual to this study or disease progression within 6 months of adjuvant anti-PD1 antibody
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
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.
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
Prior treatment with a PD-1, PD-L1, or PD-L2 blocking therapy
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
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
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.
Patients must not have received neoadjuvant treatment for their melanoma; patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, pegylated (PEG)-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
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.
Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab.
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.
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
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
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
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.
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
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
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
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:
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
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)
Has received prior therapy with PD-1, PD-L1, or CTLA-4 inhibitor
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
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
Subject eligibility will be based on PD-L1 expression as determined by a specified IHC assay.
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).
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
Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
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
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
Patients must NOT have received any class of drugs targeted to the PD-1/PD-L1 pathway
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.
Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date; patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with selinexor (Arms L and M), can start receiving the selinexor and anti-PD-1 combination without washout of the prior anti-PD-1 antibody
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
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
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
Previous exposure to CD40, PD-1, PD-L1, CTLA-4 antibodies or any other immunomodulatory agent
Prior therapy with an agent that blocks the PD-1/PD-L1 pathway
No evidence of PD for ?3 months before the first dose of study drug.
Prior treatment with anti-PD-1 or anti-PD-L1 therapeutic antibody, or pathway-targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (NCI Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:\r\n* Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization\r\n* No history of severe immune-related adverse effects (CTCAE Grade 3 and 4) from anti-CTLA-4
Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose, and no history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Patients who have received prior treatment with anti-CTLA-4 antibody may be enrolled, provided the following requirements are met:\r\n* > 6 weeks from the last dose\r\n* No history of severe immune-related adverse effects from anti-CTLA-4 antibody (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Prior therapy with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents.\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose.\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4).
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents; but patients who have received prior treatment with anti·CTLA-4 may be enrolled, provided the following requirements are met: (1) minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose; (2) no history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology for Cancer Adverse Effects CTCAE] grade 3 and 4)
(Atezolizumab-related exclusion) Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents a) Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose. No history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and >6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents. Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose. No history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4).
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents\r\n* Note:\r\n** Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n*** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n*** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] grade 3 and 4)
Has received prior therapy with an anti-CTLA4 agent
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (NCI CTCAE grade 3 and 4)
Patients who have received prior treatment with anti?CTLA-4 may be enrolled, provided the following requirements are met:\r\n* Minimum of 12 weeks from the first dose of anti?CTLA-4 and > 6 weeks from the last dose\r\n* No history of severe immune-related adverse effects from anti?CTLA-4 (CTCAE grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents\r\n* Patients who have received prior treatment with anti-cytotoxic T lymphocyte-associated antigen (CTLA-4) may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last\r\ndose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] common terminology criteria for adverse events [CTCAE] grade 3 and 4)
Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents or eribulin\r\n* Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:\r\n** Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose\r\n** No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Prior anti-PD-L1 therapies are excluded\r\n* Patients who have received prior treatment with immunotherapy including anti-PD-1 anti-CTLA-4 may be enrolled, provided that there was no history of severe immune-related adverse effects (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] grade 3 and 4)
No history of severe immune-related adverse effects from anti CTLA 4 (CTCAE Grade 3 and 4)
Prior treatment with an anti-CTLA-4 agent
Previous therapy with any PD-1 or PD-L1 inhibitor including durvalumab or anti-CTLA4 (including tremelimumab) for any malignancy.
Previous treatment with a CTLA-4, PD-1, or PD-L1 inhibitor, including prior treatment with either durvalumab or tremelimumab
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
Prior immunotherapy including but not limited to anti-CTLA4, including tremelimumab anti-PD-1, and anti-PD-L1, including durvalumab.
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4 inhibitor including tremelimumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
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
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
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
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
Any previous treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapy, including durvalumab and tremelimumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
Any previous treatment with adoptive T cells therapy, a PD1 or PDL1 inhibitor, including durvalumab or any anti-CTLA4 therapy, including tremelimumab.
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
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
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), including tremelimumab
Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
Previous therapy with any PD1 or PD-L1 inhibitor (including durvalumab) for any malignancy.
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 previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
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
Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or any anti-CTLA4, including tremelimumab
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
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti- CTLA-4, including tremelimumab
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 may have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >= 4 weeks prior to registration
Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or mitomycin C for 6 weeks prior to C1D1.
6. Part A: Prior exposure to immunotherapy such as but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines. Part B: Exclusion of prior immunotherapy exposure will be limited to anti-PD-1, anti-PD-L1, or anti-PD-L2;
Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
Has received pembrolizumab, or prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as part of any previous therapy, including trials
Subjects previously treated with T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents
Patient with melanoma, ovarian cancer, renal cell carcinoma, colorectal cancer, and other solid tumors who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 antibody; melanoma patients who received anti-PD-1 antibodies in the adjuvant setting are allowed to participate as long as their last anti-PD-1 antibody was given at least 6 months prior to their planned start of study therapy
Patients should be excluded if they have had prior systemic treatment with an anti-CTLA4 antibody and anti-PD1/PDL1 antibody; prior treatment with single agent anti-CTLA4, anti-PD1 or anti-PDL1 antibody is allowed
Subject on prior chemotherapeutic, immunomodulator (such as anti-CTLA-4, anti-PD-1 or anti-PD-L1 inhibitor), investigational, or other therapies for the treatment of cancer must wait at least 28 days after the last dose of these therapies before administration of the first dose of the IMP.
Prior treatment with PV-10 or any anti-PD-1 antibody
Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA 4 therapy.
Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint-blockade therapies, including anti-cluster of differentiation 40 (anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
For Cohort Expansion, patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) are not eligible for this study.
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
INCLUSION CRITERIA - For Parts 1-4:\n\n          -  Willing and able to provide written informed consent\n\n          -  Histologically confirmed diagnosis of a locally advanced (not amenable to curative\n             therapy such as surgical resection) or metastatic melanoma, RCC, NSCLC, urothelial\n             carcinoma, or TNBC\n\n          -  Male or female patients, age 18 years or older at the time of signing the informed\n             consent form (ICF)\n\n          -  Life expectancy > 12 weeks\n\n          -  Patients must not have received prior interleukin-2 (IL-2) therapy\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n\n          -  Measurable disease per RECIST 1.1\n\n          -  Demonstrated adequate organ function within 14 days of treatment initiation\n\n          -  Oxygen saturation ? 92% on room air.\n\n          -  Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy,\n             other prior system anticancer therapy, radiotherapy, or surgery. Clinically\n             significant toxic effect(s) of the most recent prior chemotherapy must be resolved to\n             Grade 1 or less (except alopecia and sensory neuropathy).\n\n          -  Women of childbearing potential must agree to use highly effective methods of birth\n             control. All participants must agree to use double barrier contraception during study\n             participation for at least 6 months after the last dose of study drugs.\n\n          -  Patients with stable brain metastases may be enrolled if certain criteria are met.\n\n          -  Fresh and archival tumor tissue available\n\n          -  Additional criteria may apply.\n\n        INCLUSION CRITERIA - For Part 2:\n\n          -  MELANOMA:\n\n               -  Histologically confirmed stage III (unresectable) or stage IV melanoma, as per\n                  American Joint Committee on Cancer (AJCC) staging system\n\n               -  Ocular melanoma will be excluded\n\n          -  Melanoma Subpopulation A 1st-line (1L):\n\n               -  Have not received prior anti-cancer therapy for advanced or metastatic melanoma\n\n               -  Known BRAF status, or consent to testing, as per regionally acceptable V600\n                  mutational status testing\n\n          -  Melanoma Subpopulation B (2nd- and 3rd-line (2-3L), anti-PD-1 or anti-PD-L1 therapy\n             relapsed/refractory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic progression.\n\n               -  Patients may have received no more than 1 prior anti-angiogenic therapy or\n                  cytotoxic chemotherapy regimen.\n\n          -  RENAL CELL CARCINOMA (RCC):\n\n               -  Advanced (not amenable to curative surgery or radiation therapy) or metastatic\n                  (AJCC stage IV) RCC\n\n               -  Histologically confirmed RCC with a clear-cell component.\n\n          -  RCC Subpopulation A (1L):\n\n               -  1L, patients may have not received prior anti-cancer therapy for advanced or\n                  metastatic RCC.\n\n          -  RCC Subpopulation B (2-3L, anti-PD-1 or anti-PD-L1 relapsed/refractory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n               -  Patients may have received no more than 1 prior anti-angiogenic therapy or\n                  cytotoxic chemotherapy regimen.\n\n          -  NON-SMALL CELL LUNG CANCER (NSCLC):\n\n               -  Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC\n\n                    -  Patients with nonsquamous NSCLC must lack epidermal growth factor receptor\n                       (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK)\n                       translocation\n\n          -  NSCLC Subpopulation A (1L):\n\n               -  1L, patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic NSCLC. Patients must have known PD-L1 status as per validated\n                  immunohistochemistry testing. Up to 20 patients will be enrolled in each\n                  subgroup:\n\n                    -  PD-L1 negative (PD-L1 < 1%),\n\n                    -  PD-L1 positive (PD-L1 ? 50%),\n\n                    -  PD-L1 low/intermediate (PD-L1 ? 1% - < 50%).\n\n               -  For patients who do not have known PD-L1 status, testing must be done using an\n                  FDA-approved PD-L1 test.\n\n          -  NSCLC Subpopulation B (2L, I-O therapy naïve):\n\n               -  2L, patients must have experienced disease recurrence or progression during or\n                  after one prior platinum doublet-based chemotherapy regimen for advanced or\n                  metastatic disease. Patients who received platinum-containing adjuvant,\n                  neoadjuvant, or definitive chemoradiation therapy given for locally advanced\n                  disease and developed recurrent (local or metastatic) disease within 6 months of\n                  completing therapy are eligible. Patients must not have received any prior\n                  immune-oncology regimens, including but not limited to checkpoint inhibitors such\n                  as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any\n                  other antibody or drug specifically targeting T cell co-stimulation or checkpoint\n                  pathways, indoleamine 2,3 dioxygenase pathway inhibitors, cancer vaccines,\n                  adoptive cell therapies, or other cytokine therapies.\n\n          -  NSCLC Subpopulation C (2-3L, anti-PD-1 or anti-PD-L1 relapsed/refactory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n          -  UROTHELIAL CARCINOMA (UC)\n\n               -  Histologically or cytologically documented locally advanced or transitional cell\n                  carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, or\n                  urethra. Patients with mixed histologies are required to have a dominant\n                  transitional cell pattern.\n\n               -  For patients who received prior adjuvant/neoadjuvant chemotherapy or\n                  chemo-radiation for urothelial carcinoma, a treatment-free interval of more than\n                  12 months between the last treatment administration and the date of recurrence is\n                  required to be considered treatment naive in the metastatic setting.\n\n          -  UC Subpopulation A (1L)\n\n               -  Enrollment of urothelial carcinoma 1L patients will target accrual of up to 20\n                  patients who are cis-ineligible and up to 20 patients, who after consultation\n                  with the Investigator, choose to forego front-line chemotherapy\n\n               -  Treatment naive and cisplatin-eligible patients who refuse standard of care.\n\n          -  UC Subpopulation B (1L) cisplatin-ineligible\n\n               -  Treatment naive and cisplatin-ineligible patients who meet at least one of the\n                  following criteria:\n\n                    -  Creatinine clearance (calculated or measured) < 60 mL/min\n\n                    -  Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade ? 2\n                       audiometric hearing loss\n\n                    -  CTCAE v4.03 Grade ? 2 peripheral neuropathy\n\n                    -  New York Heart Association (NYHA) Class III heart failure\n\n               -  No prior chemotherapy for inoperable locally advanced or metastatic urothelial\n                  carcinoma. Prior local intravesical chemotherapy is allowed if completed at least\n                  4 weeks prior to the initiation of study treatment.\n\n               -  Patients must not have received any prior immune-oncology regimens, including but\n                  not limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2,\n                  anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically\n                  targeting T cell co-stimulation or checkpoint pathways, indoleamine\n                  2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or\n                  other cytokine therapies.\n\n          -  UC Subpopulation C (3L, anti-PD-1 or anti-PD-L1 relapse/refractory)\n\n               -  Patients must have progressed on only one prior line of therapy that contains\n                  platinum-based chemotherapy in the metastatic setting or post platinum-based\n                  chemotherapy in an adjuvant setting with progression < 6 months.\n\n               -  Patients must have received only one prior line of therapy with an anti-PD-1 or\n                  anti-PD-L1 containing regimen, which must be their most recent anti-cancer\n                  treatment.\n\n               -  Patients must have confirmed radiographic disease progression no earlier than 4\n                  weeks after initial disease progression but within 3 months from last dose of\n                  anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n          -  TRIPLE-NEGATIVE BREAST CANCER (1-2L, I-O therapy naïve)\n\n               -  Less than 1% of tumor cell nuclei test positive for estrogen and progesterone\n                  receptors determined by using standard immunohistochemistry (IHC)\n\n               -  Human epidermal growth factor 2 (HER2) negative as determined by local\n                  pathologist, using IHC or in situ hybridization\n\n               -  Patients may have received only 1 prior line of therapy with chemotherapy,\n                  adjuvant setting excluded, or patient refuses standard of care.\n\n               -  Must not have received any prior immune-oncology regimens, including but not\n                  limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2,\n                  anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically\n                  targeting T cell co-stimulation or checkpoint pathways, indoleamine 2,\n                  3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or\n                  other cytokine therapies.\n\n        INCLUSION CRITERIA - For Parts 3 and 4:\n\n          -  RENAL CELL CARCINOMA (1L):\n\n               -  Advanced (not amenable to curative surgery or radiation therapy) or metastatic\n                  (AJCC stage IV) RCC.\n\n               -  Histologically confirmed RCC with a clear-cell component.\n\n               -  Patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic RCC\n\n          -  NON-SMALL CELL LUNG CANCER (1L):\n\n               -  Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC\n\n               -  Patients with nonsquamous NSCLC must lack epidermal growth factor receptor\n                  (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK)\n                  translocation.\n\n               -  Patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic NSCLC.\n\n        EXCLUSION CRITERIA - For Parts 1-4:\n\n          -  Use of an investigational agent or an investigational device within 28 days before\n             administration of first dose of NKTR--214\n\n          -  Females who are pregnant or breastfeeding\n\n          -  Participants who have an active autoimmune disease requiring systemic treatment within\n             the past 3 months or have a documented history of clinically severe autoimmune disease\n             that requires systemic steroids or immunosuppressive agents\n\n          -  History of organ transplant that requires use of immune suppressive agents\n\n          -  History of allergy or hypersensitivity to study drug components\n\n          -  Active malignancy not related to the current diagnosed malignancy\n\n          -  Evidence of clinically significant interstitial lung disease or active, noninfectious\n             pneumonitis\n\n          -  Prior surgery or radiotherapy within 14 days of therapy\n\n          -  Participants who have had < 28 days since the last chemotherapy, biological therapy,\n             or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib,\n             sorafenib, vemurafenib, dabrafenib, cobimetinib, erlotinib, gefitinib, afatinib,\n             osimertinib), or systemic or inhaled steroid therapy at doses greater than 10mg of\n             prednisone or equivalent before administration of the first dose of study medication\n\n          -  Participant's inability to adhere to or tolerate protocol or study procedures\n\n          -  Additional criteria may apply.
Previous therapy with histone deacetylase (HDAC) inhibitor and/or anti PD 1, anti PD L1, or anti CTLA4 immunotherapy.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti CTLA-4, anti-PD1 and anti-PD-L1 therapeutic antibodies
Last dose of prior immunotherapies including but not limited to: interferon alpha, interferon-beta, interleukin (IL)-2, conjugated IL-2, cergutuzumab amunaleukin (CEA-IL2v) , cytokines, anti-cytotoxic T lymphocyte antigen-4, anti-PD-L1, or anti-PD-1 <28 days prior to first cergutuzumab amunaleukin infusion
Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs.
Have received an anti-PD1 or anti PDL1 monoclonal antibody
Previous systemic exposure to anti-CTLA-4 antibody or anti-PD1 antibody
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
Participants may have had prior immuno-oncology (IO) therapy (including but not limited to anti-CTLA4 and anti-PD1/L1) excluding prior CSF1R directed agents for the study arm containing cabiralizumab
Patients must have prior exposure to an anti-PD1 or anti-PDL1 mAb, if eligible for immunotherapy in the judgment of the local investigator
Prior exposure to investigational immunotherapies, including anti-CTLA4, anti-OX40, anti-CD40, anti-CD27, anti-TNFR antibodies or other investigational immunotherapies, is acceptable
Has received prior therapy with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent
Immune-checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4), monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression).
ARM I INCLUSION CRITERIA: Subjects are currently on checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or antibodies to tumor necrosis factor family including OX40) or tumor vaccine for systemic disease who develop new brain metastases, must have documented stable systemic disease within 30 days of signing consent
ARM I INCLUSION CRITERIA: Subjects who have completed prior checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or antibodies to tumor necrosis factor family including OX40) or tumor vaccine for systemic disease but are now off therapy with documented stable systemic disease within 30 days of signing consent may be enrolled after discussion with the Merck & Co clinical team
Prior therapy with an anti-PD-1, anti PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents
Prior or concurrent immunotherapy, including treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody; tumor vaccines; interferon, or interleukins.
Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies for their metastatic disease
No prior treatment with cancer immunotherapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 anti- (PD-L2) antibodies, excluding therapeutic anticancer vaccines
Patients can be either naive for any previous systemic treatment or have had any number of prior systemic therapies. However, patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti-CTLA-4 immune checkpoint inhibitors.
Patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti- CTLA-4 immune checkpoint inhibitors.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti CTLA-4 antibody
Prior exposure to immune-mediated therapy, including but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD1, anti –PD-L1, or anti-programmed death ligand 2 (PD-L2) antibodies, including therapeutic anticancer vaccines is NOT permitted
Has prior exposure to anti-PD1/PD-L1 or anti-CTLA4 therapy
Prior treatment with anti-PD-1/PD-L1, and anti-CTLA-4 is NOT allowed; prior intravesical Bacillus Calmette–Guérin (BCG) therapy is allowed
No prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, including therapeutic anticancer vaccines; the exception to this is those whose tumors are microsatellite instable-high (MSI-hi) and are refractory to anti-PD1 monotherapy
Prior checkpoint inhibitor therapy including anti-PD1, anti-PD-L1, anti-CTLA4, anti- CD137, or anti-PD-L2 therapy
Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies\r\n* Prior cancer vaccines and cellular immunotherapy are permitted
Exclusion criteria related to study medication (any cancer immunotherapy including CD137 agonists, anti-PD-1, anti-PD-L1, or anti-CTLA4 or any MEK or ERK inhibitor)
Colorectal patients are excluded if they have had prior systemic treatment with an anti-CTLA4, anti-PD1 or PDL1 antibody; pancreatic patients are excluded if they have previously received anti-CTLA-4 therapy; prior PD-1 or PDL1 therapy will be permitted for pancreas patients
Patients may not have had prior therapy with a checkpoint inhibitor (e.g. anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy)
Prior therapy with atezolizumab or other immunotherapies including CD137 agonists, anti-programmed death (PD)-1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and anti-PD-L1 therapeutic antibodies
Prior history of receiving immune modulators including, but not limited to, anti-CTLA4, anti-PD1, anti-PD-L1
Tumor progression or recurrence during or after treatment with anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4, or other immune checkpoint inhibitor where the most recent dose was given within 3 months prior to study registration
Patients must not have received prior anticancer therapy with any immune checkpoint inhibitors such as anti-CLTA-4, anti-PD1, or anti-PD-L1
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody
patients who have received all therapy known to confer clinical benefit (including anti-PD-1 or anti-PDL1 therapies, if relevant), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Patients with anti- PD-1 or anti-PDL1 experience must have a minimum of 60 days between the last dose of the previous anti PD-1/PD-L1 and Cycle 1 Day 1 of BI 754091 treatment.
patients who are anti-PD-1 and anti-PDL-1naïve but have failed conventional treatment (excluding anti-PD-1 treatment), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies.
No prior immune checkpoint inhibitors (e.g., anti-CTLA4, anti-PD-1 or anti-PDL1 are allowed
Patients with ongoing toxicities related to prior therapies targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody are excluded
Patients must have no more than one prior systemic therapeutic regimen. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. No prior anti-CTLA4 therapy. Prior anti PD-1 or anti-PDL-1 antibody therapy is acceptable.
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-cytotoxic T-lymphocyte-associated protein (CTLA) 4 antibodies
Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents
Prior therapy with anti-PD1, anti-PD-L1 or anti-cytotoxic T-lymphocyte protein (CTLA)-4 antibody
Subjects must have no prior exposure to immunotherapy, such as, but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines
Patients with a history of prior treatment with immunotherapy agents (including, but not limited to: interleukin [IL]-2, interferon, anti-PD-1, anti-PD-L1, anti-programmed cell death 1 ligand 2 [PD-L2], anti-cluster of differentiation [CD]137, anti-tumor necrosis factor receptor superfamily member 4 [OX-40], anti-CD40, or anti-cytotoxic t-lymphocyte-associated protein 4 [CTLA-4] antibodies)
Prior exposure to immune-mediated therapy, including but not limited to, other anti cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
Prior immunotherapy is allowed (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations), except for the patients enrolled to the immunotherapy naïve group of the phase IB dose expansion.
Patients with a history of prior treatment with anti-CTLA-4, anti-PD 1 antibody, or anti-PDL1 antibody
Prior exposure to immune-mediated therapy, including anti-PD-1, anti-PD-L1 (including durvalumab) or anti-CTLA-4 directed therapy (including tremelimumab); therapeutic anticancer vaccines are not included in this category; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
Prior exposure to immunotherapy including, but not limited to, anti-PD1 or anti-PDL1 antibodies is allowed but not required.
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, or anti-programmed cell death-1 (PD-1) or anti-PD-L1 therapeutic antibodies
Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior exposure to anti-PD-1, anti-PD-L1, CCR2/5, or anti-CTLA4 antibodies
Patients who have had prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g. anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA-4], anti-programmed death-1 [anti-PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD]137, anti-CD40, anti-OX40)
Patients who have had prior treatment with anti-PD1 or anti-CTLA4 therapy
Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed death-1 [PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD] 137, anti-CD40, anti-OX40)
Patients who have had a grade one or grade two gastrointestinal adverse event during or after receiving anti-CTLA-4, anti-PD1 or anti-PD, without a colonoscopy verifying complete resolution of the adverse event
Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks
Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti?CTLA-4 in the adjuvant setting would be permitted.
Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic antibodies, or any other antibody or drug targeting T-cell costimulation.
PRIOR/CONCURRENT THERAPY CRITERIA: Prior treatment with an anti-PD-1 or anti-PDL1 is not required
Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
Patients must not have any prior exposure to immunotherapy such as, but not limited to anti-programmed death 1 (PD-1) or anti-PD-L1 antibodies; prior exposure to the following is allowed: anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, live attenuated vaccines, anti-EGFR agents and sargramostim (GM-GSF)
Subject had prior exposure to immunotherapy, including, but not limited to, other anti- CTLA-4,anti-PD-1, anti-PD-L1 monoclonal antibody or inhibitor, cell-based therapies, or cancer vaccines
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibodies
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior exposure to tremelimumab or durvalumab or other anti-CTLA-4, anti-PD-1, anti-PD-L1 antibodies
No prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody.
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
Received therapy with any immunotherapeutic agents including, but not limited to, any anti-PD1 or anti-PDL1 antibody therapy, with these exceptions: Melanoma patients having received and progressed on anti-CTLA4 (cyctotoxic T lymphocyte-associated antigen 4) may participate in the trial; Bladder cancer patients having received intra-vesical BCG may participate in the trial.
Prior treatment with an anti PD-1, anti PD-L1, or anti CTLA-4 agent; participants who entered clinical remission with one of those agents and proceeded to ASCT without intervening relapse may be eligible after discussion with the study chair; note that for patients who enter remission with checkpoint blockade therapy, this will not count towards the 3 lines of prior therapy
Prior immunotherapies including but not limited to CD137, anti-PD-1, anti-PD-L1, and CTLA4.
CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4, anti-PD-1, and anti-PD-L1 therapies
Patients who have had prior exposure to checkpoint blockade therapy, such as anti-PD-1/PD-L1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-CD137, and anti-OX40 antibody therapy, are not eligible
Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
Prohibited prior treatments and/or therapies: a) prior therapy with an anti-killer cell immunoglobulin-like receptors (KIR), anti-programmed cell death 1 (PD-1), or anti-programmed cell death ligand 1 (PD-L1), antibody ; b) prior treatment regimens with any immune cell modulating antibody such as anti-cluster of differentiation (CD)137 and anti-OX40; however, prior anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy is allowed if the last dose is 101 days or more from the first dose of study drug; c) exposure to any other investigational drug within 2 weeks prior to the first dose of study drug (within 101 days for anti-CTLA4 therapy); d) any anti-cancer therapy (e.g., chemotherapy, biologics, vaccines, radiotherapy with curative intent, or hormonal treatment) within 2 weeks prior to the first dose of study drug administration (within 101 days for anti-CTLA4 therapy administration); e) use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug; the use of the inactivated seasonal influenza vaccine (Fluzone) is allowed; f) systemic corticosteroid at immunosuppressive doses (> 10 mg/day of prednisone or equivalent), must be discontinued at least 2 weeks prior to enrollment
Prior therapy with anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody
Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other TLR agonists, MEDI4736 or checkpoint inhibitors, such as anti-CTLA4 and anti-PD1/anti-PD-L1 antibodies.
Received prior therapies: ibrutinib, or other BTK inhibitor and/or anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cluster of differentiation (CD)137; patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) (ipilimumab, tremelimumab) will NOT be excluded and are eligible for inclusion
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti CTLA4
Prior BTK inhibitor or anti PD1, anti PDL1, anti PD-L2 and anti-CD137, anti-cytotoxic T-lymphocyte associated antigen (CTLA-4) antibody
Patients with a history of prior treatment with anti-PD-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies, or who have received both GVAX or CRS-207 will be excluded
Prior exposure to tremelimumab or MEDI4736 or other anti-CTLA-4, anti-PD-1, anti-PDL1 antibodies
Ocular melanoma; and have received no more than one line of systemic therapy for metastatic disease. Patients must not have received immune modifying agents (eg. anti PD-L1, anti PD-1, anti CTLA4, TNF agonist, etc.) for metastatic disease, or
Cutaneous/acral melanoma; and have 1) only previously received systemic therapy for advanced/metastatic disease with the following therapies: BRAF and MEK inhibitors, anti PD-L1, anti PD-1, or anti-CTLA4 and 2) have received checkpoint inhibitor (anti PD-L1, anti PD-1, or anti-CTLA4) based treatment as most recent line of therapy on which disease progressed, as long as progression did not occur in the first 3 months of receiving checkpoint inhibitor treatment. Arm 2 only:
Prior histone deacetylase (HDAC) inhibitor and/or anti-PD1, anti-PDL1, anti-PD-L2, anti-CD137 or anti-cytotoxic T- lymphocyte associated antigen 4 (CTLA-4) antibody allowed as long patient received clinical benefit from it, best response was not progressive disease and it was not the most recent treatment
Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies. For subjects with metastatic melanoma, prior treatment with CTLA-4-blocking antibody is permissible.
Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance.
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody; neuroblastoma (NB)-patients who have received prior anti-cytotoxic T-lymphocyte antigen (CTLA)-4 antibody therapy are eligible assuming such therapy was discontinued within 28 days of enrollment
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody.
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
Recipient of any blood product and immunotherapy (such as anti-PD1, anti-PDL-1 and anti-CTLA4) within 3 months of enrollment;
Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
Prior exposure to immunotherapy, such as, but not limited to, other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, excluding therapeutic cancer vaccines
Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 8 weeks prior to enrollment
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)
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
In the NSCLC CIT-Naïve expansion cohort in Phase 1b, prior treatment with anti-PD?L1/PD-1 and/or anti-CTLA-4 (investigational or approved) is not allowed
No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Participants with a history of treatment with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or other investigational agents that target immune checkpoint inhibitors
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti PD1, and anti-PD-L1 therapeutic antibody
Prior treatment with checkpoint inhibitors and other immunotherapy treatments, including anti-LAG-3, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies, if less than 5 half lives before study drug administration
Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or anti-CD38 antibody, or allogeneic stem cell transplantation
Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are approved therapies
History of prior treatment with immune checkpoint antibodies (e.g. anti-PD1, anti-PDL1, anti-CTLA4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40)\r\n* Prior intravesical treatment with Bacillus Calmette-Guerin (BCG) is allowed; however, the last dose must be at least 6 weeks from time of enrollment and patients must have documented progressive disease at least 6 weeks from completion of last BCG
Patients that plan to receive off-label use of anti-PD1 or anti-PDL1
Patients must not have had prior exposure to any immune checkpoint inhibitors including anti-PD-1, anti-PD-L1 gents, anti-PD-L2 agents, or anti-CTLA-4 monoclonal antibodies
Patients who have previously received anti-PD1 or anti-PD-L1 therapy; patients who have previously received anti-CTLA-4 therapy (e.g. ipilimumab) are eligible for study
Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy
Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
For subjects who have received prior checkpoint inhibitors:
Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE related to checkpoint inhibitors, not have experienced recurrence of an AE related to checkpoint inhibitors if re challenged, and not currently require maintenance doses of corticosteroids.
Prior exposure to cancer immunotherapy including any immune checkpoint inhibitor and/or cancer vaccines
Refractory to prior checkpoint inhibitor therapy (received less than 6 months of treatment)
Prior treatment with immune checkpoint inhibitors and MEK inhibitors
Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.
Patients must have progressed on prior approved checkpoint inhibitor therapy, not tolerated approved checkpoint inhibitor therapy, or have a contraindication to approved checkpoint inhibitors; patients with stable disease after approved checkpoint inhibitor therapy will also be eligible
Phase II: Subjects who have progressed on first-line systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy) who are candidates for second-line systemic therapy.
Phase II: Subjects with an EGFR or ALK mutation who are no longer candidates for TKI therapy and have progressed on standard systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy).
Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)
Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimens
For immune checkpoint naïve CRPC patients all of the following must apply:
For immune checkpoint naïve patients all of the following must apply:
For other immune checkpoint naïve tumor cohort all of the following must apply:
Prior exposure to either ipilimumab or combined checkpoint blockade
Patients who have had prior therapy with immune checkpoint inhibition or or indoximod are excluded from the trial.
Known history of allergy or intolerance which, in the opinion of the investigator, was an unacceptable adverse reaction attributed by the investigator to any prior anti-neoplastic therapy specifically targeting T-cell costimulation or immune checkpoint pathways – i.e. nivolumab (Opdivo), pembrolizumab (Keytruda), atezolizumab (Tecentriq), ipilimumab (Yervoy), etc.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies;
History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
Cohort B only: prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
Prior checkpoint inhibitors/blockade in the last 12 months.
Participants must not have a history of any significant drug allergy (such as anaphylaxis or hepatotoxicity) to prior anti-cancer immune-modulating therapies (eg, checkpoint inhibitors and T-cell co-stimulatory antibodies)
Prior exposure to T cell checkpoint inhibitor therapies.
Previous treatment with and disease progression on a combination of a VEGF inhibitor and an immune checkpoint inhibitor. Patients who have been treated with and have progressed on a single agent VEGF inhibitor OR an immune checkpoint inhibitor will not be excluded
At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment
Failure to recover from prior side effects of immune checkpoint inhibitor therapy to =< grade 1; NOTE: Patients will not be excluded for adrenal insufficiency or hypothyroidism secondary to immunotherapy provided they are receiving hormonal replacement
No limit is placed on prior systemic treatment, but subjects must be eligible for immune checkpoint inhibitors therapy, for a Food and Drug Administration (FDA) approved indication
Prior treatment with immune checkpoint inhibitors
Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor (e.g., uncontrolled immunologic disorders, active hepatitis, active colitis, active pneumonitis, uncontrolled/active hormone gland problems - including thyroid, pituitary, adrenal glands and pancreas)
History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
Intolerance to immune checkpoint inhibitor therapy as defined by the occurrence of an adverse drug reaction requiring drug discontinuation (dose escalation cohorts), concurrent anticancer treatment or immunosuppressive agents.
All prior chemotherapy must be at least 4 weeks prior to TATE and free from treatment-related toxicity. No gap is needed for prior PD-1 checkpoint inhibitors in NSCLC patients.
Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), within 14 days of the first dose of study treatment.
Immune checkpoint inhibitor therapy within 30 days of first dose of study treatment.
Failure to respond to standard of care checkpoint blockade therapy or previously responding patients who progress on checkpoint blockade therapy
Patient must have received prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior mTOR inhibitor or TKI treatment as monotherapy or in combination with immune checkpoint inhibitor are allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry.
Last dose of immune checkpoint inhibitor therapy must have been received 4 or more weeks before start of study treatment
Prior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy.
Prior therapy with T-cell therapy, including an immune checkpoint inhibitor
Patients who have had prior exposure to immune checkpoint inhibitors are not eligible; please contact principal investigator, Maria Matsangou at 312-926-4248 for specific questions on potential interactions\r\n* NOTE: Immune checkpoint inhibitors working through OX40 are an exception (for example, MEDI6383, MEDI6469, MEDI0562, oxelumab, and PF-04518600) and are permitted >= 28 days prior to study registration
Previous treatment with immune checkpoint inhibitors
Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
Immunotherapy with immune checkpoint inhibitors, cell-based therapies, or cancer vaccines
Has received prior therapy with any immune checkpoint inhibitor
Prior exposure to T cell checkpoint inhibitor therapies, including durvalumab and tremelimumab
Subjects with disease recurrence or progression After therapy with an immune checkpoint inhibitor and platinum-based chemotherapy i) either 1st line chemotherapy followed by 2nd line checkpoint inhibitor, or ii) 1st line combination of checkpoint inhibitor and chemotherapy
Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)
Unacceptable toxicity with prior checkpoint inhibitor
Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology doublet used as the prior line of therapy)
History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
Known intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE leading to drug discontinuation;
Prior anticancer therapy is allowed, including prior checkpoint inhibitor treatment.
Prior immunotherapy with checkpoint inhibitors
Any other illness or condition that in the investigator’s opinion would adversely affect the safety of checkpoint inhibitor therapy
Eligible for checkpoint inhibitor immunotherapy (pembrolizumab) per standard of care
Prior immunotherapy with immune checkpoint inhibitors
Previous treatment with talimogene laherparepvec or other herpes virus based therapy; (prior therapy with checkpoint inhibitors and/or other immunotherapy is allowed)
History of grade 3 or 4 bowel toxicity from immune checkpoint inhibitor within 12 weeks of registration
Previous treatment with checkpoint inhibitor drugs
Subjects who have received prior immune checkpoint inhibitors or an IDO inhibitor (except select Phase 2 cohorts evaluating I/O relapsed or I/O refractory MEL). Subjects who have received experimental vaccines or other immune therapies should be discussed with the medical monitor to confirm eligibility
Prior treatment with CD137 agonists or immune checkpoint blockade therapies.
Grade 3 colitis, hepatitis, pneumonitis uveitis, myocarditis, myositis, CNS toxicity or autoimmune related neuromuscular toxicity such as myasthenia gravis associated with the administration of an immune checkpoint inhibitor
Have discontinued previous experimental therapies and checkpoint inhibitor antibodies at least 28 days prior to the Randomization Visit
Subjects who received prior therapy with checkpoint inhibitor
Prior treatment with any drug that targets T cell co-stimulation pathways(such as checkpoint inhibitors)
No prior history of immune checkpoint modulator therapy
Any prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anti-cancer therapy than that described in inclusion criteria
Patients with a history of Grade ?2 gastrointestinal symptoms (e.g., diarrhea, colitis) during prior checkpoint inhibitor treatment should be discussed with the Idera Medical Monitor during the Screening Period before starting study treatment.
Patients in Phase 2 expansion cohort A will have experienced disease progression with 1 systemic treatment containing a checkpoint inhibitor. Any prior liver directed therapy is acceptable.
Has plans to receive cytotoxic chemotherapy, immune checkpoint inhibitors (eg CTLA-4 blockade), sipuleucel-T, radiopharmaceuticals, abiraterone or other experimental therapy during this study period
Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
Prior treatment with clusters of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, systemic immunostimulatory agents, or systemic immunosuppressive medications
Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs; (immune checkpoint inhibitors that are antibody-based will only require 28 days before enrollment)
Patient receiving any investigational or experimental agents other than checkpoint blockade immunotherapy
Patients previously treated with immune checkpoint inhibitor therapy are eligible
Not a candidate for treatment with an immune checkpoint inhibitor (e.g., failed or did not tolerate prior therapy, or due to co-morbidities, pre-existing autoimmune disease, drug unavailability or standard of care)
Prior treatment with CD137 agonists or immune checkpoint blockade therapies
Immune therapy (monoclonal antibody therapy, checkpoint inhibitors) within 4 weeks.
Any previous immunotherapy with immune checkpoint inhibitors such was nivolumab, atezolizumab and others in the class.
Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline
Prior treatment with CD137 agonists or other immune checkpoint blockade therapies, including anti-CTLA-4 therapeutic antibodies
Prior history of Grade 3 or greater drug-related diarrhea/colitis during treatment with checkpoint inhibitors or other immunotherapy treatments.
Has had prior monoclonal antibody (mAb) targeting immune checkpoint proteins, for distant metastatic melanoma and have progressed or have developed intolerable side effect
Patients who are eligible to receive combined dual immune-checkpoint blockade therapy with ipilimumab and nivolumab, per referring oncologist
Candidate to undergo immune checkpoint inhibitor (ICI) therapy for SCLC or NSCLC (ICI as any line of chemotherapy is acceptable) as deemed by individual’s treating oncologist
Immune checkpoint inhibitor therapy within 30 days of the first dose of study treatment
Patients must have relapsed/refractory disease, with at least one line of prior chemotherapy, but =< 2 prior lines of treatment, for Hodgkin lymphoma; NOTE: patients must not have had prior immune checkpoint inhibitors; however, there are no other limitations to prior agent or regimen types
Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC.