Patients should be excluded if they have had prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Participants should be excluded if they have had prior treatment with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; prior immune modulating therapy including vaccines may be eligible; prior immune events must be evaluated and the risk for new events which may represent continued sub clinical disease or a new process at previously damaged site or immune potentiation (e.g. ipilimumab followed by IL2 causing bowel perforation, ipilimumab followed by indoleamine 2,3-dioxygenase [IDO] inhibitor resulting in clinical hypophysitis); please keep in mind that inflammatory events may occur weeks to months following the last dose of ipilimumab and possibly nivolumab; assessment of potential effects of prior therapy should include:\r\n* Immune status\r\n* Organ damage\r\n* Risk of autoimmunity\r\n* Immunopotentiation
Prior treatment with cluster of differentiation (CD)137 agonists, anti-cytotoxic T-lymphocyte-associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD?1), or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibody or pathway-targeting agents
Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
No prior treatment with an immune checkpoint inhibitor (anti-programmed cell death [PD]-1, anti-PD-L1, anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] monoclonal antibody)
No prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
Patients with prior treatment with anti-programmed cell death (PD)-1, anti- programmed cell death ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 therapeutic antibody or other similar agents
No concurrent or prior systemic or local anti-cancer therapy for RCC is permitted; examples of these prohibited therapies include:\r\n* Radical or partial nephrectomy for prior RCC\r\n* Metastectomy for RCC\r\n* Radiation therapy to the renal bed or any distant metastatic sites\r\n* Antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or investigational agents for treatment of RCC\r\n* Prior treatment with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Has received prior therapy with an anti-programmed death 1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
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
Fresh tumor tissue available for cellular characterization and programmed cell death protein 1 (PD-L1) status.
Has received prior therapy with an anti-programmed death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (eg, cytotoxic T-lymphocyte associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137]).
Have received any previous systemic therapy (including investigational agents) targeting PD-1/programmed cell death ligand 1 (PDL-1) or PD-1/PDL-2 signaling pathways (including previous participation in Merck MK-3475 trials). Prior treatment with olaratumab is allowed. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, is not permitted.
Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
There is no limit to the number of lines of prior therapy; prior anti-programmed cell death (PD)-1 or anti-PD-ligand (L)1 therapy and other immunotherapies are allowed
SAFETY RUN-IN: Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-cluster of differentiation 137 (CD137) antibody, or anti-cytotoxic T-lymphocyte –associated antigen-4 (CTLA-4) antibody
RANDOMIZED PHASE II CLINICAL TRIAL: Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte –associated antigen-4 (CTLA-4) antibody
Has received previous treatment with an immunomodulatory therapy (e.g. anti-programmed cell death-1/anti-programmed cell death-ligand 1 [anti-PD-1/anti-PD-L1] or cytotoxic T-lymphocyte-associated protein 4 [CTLA 4] agent) and was discontinued from that therapy due to a Grade 3 or higher irAE.
Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP.
Prior treatment with PD-1 and programmed death ligand (PD-L)1 inhibitors
Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral immune-related testing and for anti-programmed cell death (PD)-1
Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (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 systemic anti-cancer therapy including investigational agents or has used an investigational device within 28 days prior to the first dose of study treatment. (Notes: Participants must have recovered from all AEs due to previous therapies to ?Grade 1 or baseline. Prior exposure to immunotherapeutics is allowed, including programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, provided the participant did not experience ?Grade 3 drug-related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor.
Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti- Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
Confirmed tumor programmed death?ligand 1 (PD-L1) evaluation as documented through central testing of a representative tumor tissue specimen
One prior disease progression episode on or after vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, cabozantinib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) administered for the treatment of RCC. Prior programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) treatment in addition to 1 prior VEGF-targeted treatment is allowed.
Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
Treatment with an investigational agent within 4 weeks of starting study treatment or prior treatment with a checkpoint inhibitor (cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) antibodies).
Has had prior treatment with an anti-Programmed-cell death receptor-1 (PD-1) antibody, anti-the ligand to programmed-cell death 1 (PD-L1) antibody or anti-the ligand to programmed-cell death 2 (PD-L2) antibody
Prior treatment with clusters of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockage therapies, anti-programmed death protein-1, anti-program death-ligand 1, mitogen-activated protein kinase (MEK) inhibitor
Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.
Has received prior therapy with an anti-programmed death (PD)-1, anti-programmed death ligand (PD-L)1, or anti-PD-L2 agent
Prior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class or with an anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PDL1), anti- programmed cell death 1 ligand 2 (PDL2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibodies
Prior VEGF targeted therapies for renal cell carcinoma (RCC) including adjuvant or neoadjuvant treatments; in phase 1 only, one prior therapy with high dose IL-2 or anti-programmed cell death (PD)-1 compound alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting drug is allowed on the trial
Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a Merck pembrolizumab (MK-3475) clinical study
Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD ligand-1 (PD-L1) or PD ligand-2 (PD-L2), anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways, or cancer vaccine
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
Programmed death ligand 1 (PD-L1) expression on ? 1% of tumor cells by validated immunohistochemistry assay
Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
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
Patients with a history of prior treatment with ipilimumab, anti-programmed cell death protein 1 (PD 1) antibody, or cluster of differentiation (CD)137 agonist therapy are ineligible for the ipilimumab arm, but are eligible for the nivolumab arm
Has received prior therapy with an anti-programmed cell death (PD)-1, anti- programmed cell death 1 ligand (PD-L)1, or anti-PD-L2 agent
Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation 137 (CD137), or anti-cytotoxic t-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); has participated in another MK-3475 clinical trial
Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent
Have no limits on prior lines of therapy or may be treatment-naive if in need of palliative RT provided the patient has not received prior anti-programmed cell death protein 1(PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2) therapy
Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti–programmed cell death 1 ligand 1 (PD-L1), or anti–programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines
Has received prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand (PD-L)1, or anti-PD-L2 agent (for Arm A only)
Received prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent
Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti- programmed cell death ligand 2 (PD-L2) agent
Any previous treatment with a programmed cell death protein 1 (PD1) or programmed cell death ligand 1 (PD-L1) inhibitor, including durvalumab
Prior treatment with programmed cell death (PD)-1, PD-ligand (L)1, cytotoxic T lymphocyte-associated protein 4 (CTLA 4) targeted therapy, or tumor necrosis factor receptor superfamily (TNFRSF) agonists including CD134 (OX40), CD27, CD137 (4-1BB), and CD357 (glucocorticoid-induced tumor necrosis factor receptor family-related protein [GITR])
Patients who have previously received prior pembrolizumab or programmed cell death 1 ligand 1 (PD-/L1) blockade therapy; adjuvant interferon alpha (IFN-a), is allowed if last dose was received at least 6 months of starting study treatment
Subjects who have received prior immune checkpoint inhibitors (e.g., anti-programmed cell death protein 1 [PD-1], anti-PD-L1), anti-CD40
Has experienced grade 3-4 intracranial toxicity (hypophysitis or CNS toxicity) with either prior intracranial radiation, anti programmed cell death-1 (PD-1), or cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy
Any number of previous treatments with the exception of previous inhibitors of programmed cell death 1 (PD-1), PD-L1, or programmed cell death 1 ligand 2 (PD-L2); other prior systemic therapies must have been administered at least 2 weeks before administration of pembrolizumab; the exception to this is ipilimumab which must have been administered at least 4 weeks prior to the start of pembrolizumab; patients are not required to have had prior systemic therapy
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, or anti-PD-L2 agent
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 treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA4), anti-programmed cell death protein 1 (PD-1), or anti-programmed death ligand 1 (PD-L1) (approved or investigational agent)
Patients should be excluded if they have had prior systemic treatment with an anti?programmed cell death protein 1 (PD?1), anti?PD?L1, anti?programmed cell death 1 ligand 2 (PD?L2), anti?cytotoxic T-lymphocyte-associated protein 4 (CTLA?4) antibody, or any other antibody or drug specifically targeting T?cell costimulation or immune checkpoint pathways
Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-programmed cell death-ligand 2 (PD-L2) agent; prior therapy with paclitaxel or docetaxel
History of previous exposure to an anti-programmed cell death 1 (PD-1)/PD-L1 agent
Patients who have had prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), anti-cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
Has received prior therapy with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-tumor necrosis factor receptor superfamily, member 9 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Prior treatment with immune therapy (including but not limited to cluster of differentiation [CD]137, OX40, programmed cell death [PD]-1, PD-L1 or cytotoxic T-lymphocyte antigen 4 [CTLA4] inhibitors)
Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Prior immunotherapy with programmed cell death 1 (PD1) inhibitor (i), programmed cell death ligand 1 (PDL1)i, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vaccines is allowed
Has received prior therapy with an anti-PD-1, anti-programmed cell death ligand 1 (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 antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); prior therapies with other immunomodulatory agents must be reviewed by the principal investigator (PI) and may be cause for ineligibility
Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand (PD-L) 1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or chimeric antigen receptor (CAR)-T cell therapy or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
No anti-cancer therapy (chemotherapy, biologic therapy, or immunotherapy) in the 3 weeks prior to the T cell infusion (and all hematologic effects have resolved); no prior immunotherapy with checkpoint blockade (i.e. anti-programmed cell death 1 [PD1] inhibitor, programmed cell death ligand 1 [PDL1] inhibitor or cytotoxic T-lymphocyte-associated protein 4 [CTL4] -antagonist or similar agent) in the 6 months prior to the T cell infusion (and all clinically significant related side-effects related must be resolved)
Prior immune checkpoint targeting drugs (e.g., anti-programmed cell death 1 [PD1], and programmed cell death ligand 1 [PDL1], anti-killer cell immunoglobulin-like receptors [kir], anti-cluster of differentiation [CD] 137...etc)
Has experienced a dose limiting toxicity on treatment with either prior radiation or anti programmed cell death 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) inhibitor therapy
Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137
Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Has received prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); prior treatment with interferon alfa is allowed; patients with history of allergic or hypersensitivity reaction to interferon alfa are excluded
Progression of disease while on anti-programmed death-1 (anti-PD-1) or anti-programmed cell death 1 ligand 1 (anti-PD-L1) therapy for melanoma and non-small cell lung carcinoma (NSCLC) patients
Prior exposure to any anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) antibody
Patients receiving anti programmed cell death protein 1 (PD-1) immunotherapy such as pembrolizumab or nivolumab, or human cytotoxic T-lymphocyte antigen 4 blocking antibody such as ipilimumab should wait 8 weeks before Melphalan/HDS treatment.
Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy
Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy
Received or ineligible for platinum-based therapy and Programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy
Prior exposure to any agent (approved or investigational) that blocks the programmed cell death-1 (PD-1)/PD-L1 pathway.
Part 1: Has received prior therapy with cancer vaccines, or compounds targeting programmed cell death ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or Mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated Kinase (MEK).
Subject has received previous treatment with any anti-PD-1 (Programmed death 1) or anti-PD-L1 (PD-1 ligand receptor) antibody
Any number of prior therapies (including none). For subjects who have received prior systemic treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Programmed death 1 (PD-1) and/or Programmed death-ligand 1 (PD-L1) therapy, the last monoclonal antibody administration should be no less than 6 weeks prior to start of this protocol therapy and all prior side effects must have resolved to grade 1 or less by the time of the start of this protocol therapy.
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
Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxicT-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy for HCC.
Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137).
Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any anti-programmed cell death protein 1 (PD1) monoclonal antibody (anti-PD-1) dose
Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing
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
Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, BRAF, or mitogen-activated protein kinase [MEK] agents); patients may have had prior anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment; patients may not have had any prior programmed cell death (PD)-1/PD-ligand (PD-L)1 agent in the adjuvant setting
Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer; note: prior cytotoxic chemotherapy or biologic/targeted therapy for a different cancer is allowable; however, a prior anti-programmed cell death (PD)-1, anti-PD-L1, or anti-programmed cell death 1 ligand 2 (PD-L2) agent is not permitted
Any previous treatment with an anti-programmed cell death 1 (PD1) or PD-L1 inhibitor, including MEDI4736
Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
For melanoma patients, patients must have received prior programmed cell death protein 1 (PD-1) therapy and have progressed immune-related progressive disease (irPD) by immune-related Response Criteria (irRC)
NSCLC patients who have received prior therapy with an agent directed at PD-1, PD-L1, or programmed cell death 1 ligand 2 (PD-L2)
Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation 137 (CD137), ziv-aflibercept or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)(prior treatment with bevacizumab is not an exclusion criteria)
Prior therapy with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, anti programmed cell death 1 (PD-1), or an experimental immune system-targeted therapy
Prior treatment with immune-modulatory agents including, but not limited to: interleukin (IL)-2, cytotoxic T-lymphocyte antigen 4 (CTLA)-4 blockade, programmed death (PD-1)-1/programmed death-ligand 1 (PD-L1) blockade, cluster of differentiation (CD)40 stimulation, CD137 stimulation with the exception of INF-alpha given as adjuvant treatment for high-risk, surgically resected melanoma
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti- programmed cell death 1 ligand 2 (PD-L2) agent
Patients with a history of prior treatment with ipilimumab, anti-programmed cell death 1 (PD1) antibody, cluster of differentiation (CD)137 agonist or anti-CD 40 antibody
Subjects may have received any number of the following therapies: cytokine therapy (e.g. high dose interleukin-2) or checkpoint inhibitor therapy (e.g. anti-programmed cell death [PD]1/programmed cell death ligand [PDL]1, anti-cytotoxic T-lymphocyte-associated protein [CTLA]4) or mechanistic target of rapamycin (mTOR) inhibitor therapy (e.g. everolimus, temsirolimus)
Prior treatment with anti-PD-1, anti-programmed death-ligand (PD-L)1, anti-PD-L2 antibody
Patients with previous exposure to anti-programmed cell death (PD)-1 or anti-programmed cell death ligand 1 (PDL-1) will not be eligible
Patients who have previously received ipilimumab, programmed cell death 1 (PD-1) inhibitors or programmed cell death-ligand 1 (PD-L1) inhibitors are excluded
Patients with a history of prior treatment with ipilimumab, anti-programmed cell death 1 (PD 1) antibody, cluster of differentiation 137 (CD137) agonist or other immune activating therapy such as anti-cluster of differentiation 40 (CD 40) antibody
Patients with a history of prior treatment with ipilimumab, anti-programmed cell death (PD) 1 antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody
Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PDL-2, or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody (or any other antibody targeting T-cell co-stimulation pathways)
Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)
Prior treatment with cluster of differentiation (CD) 137 agonist, anti-programmed death (PD) 1, or anti-programmed death ligand (PD-L) 1 therapeutic antibody or pathway-targeting agents
Previous treatment with pembrolizumab, nivolumab, or other programmed cell death-1 antibody (anti- PD-1) or PD-1 ligand-antibody (anti-PD-L1) agents.
Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
HER2/neu protein negative and programmed cell death ligand 1 (PD-L1)-positive
Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway) (certain exceptions may apply)
Subjects must not have received immunotherapy with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte antigen (CTLA-4) targeted therapy.
Central determination of programmed cell death ligand 1 (PD-L1) tumor status
Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-1 (anti-PD-L1), 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) or previously participated in any pembrolizumab (MK-3475) clinical studies
Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways)
Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing
Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Had prior treatment with any anti-programmed cell death 1 (anti-PD-1), or anti-programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms. Examples of such antibodies include antibodies against indoleamine-2,3-dioxygenase (IDO), PD-L1, interleukin 2 receptors (IL-2R), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR).
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)
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.
Participant has received prior treatment with any anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immunoregulatory receptors or mechanisms.
Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression
Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
Prior anti- Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), Programmed death-1 (PD-1), or Programmed death ligand-1 (PD-L1) or other immune checkpoint mAb exposure.
Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), antiprogrammed death-ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
Tumor tissue available for programmed cell death ligand 1 (PD-L1) testing
Prior therapy with an anti-programmed cell death-1 (PD-1) or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) study
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
Receipt of prior immunomodulatory agents, including programmed death-1 or PD-L1 targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 targeted therapy including ipilimumab (this exclusion criterion does not apply to participants enrolled in Expansion Cohort A)
Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
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
Inclusion Criteria:\n\n        For inclusion in the study, patients should fulfill the following criteria:\n\n          -  Aged at least 18 years\n\n          -  Documented evidence of Stage IV NSCLC\n\n          -  No sensitizing EGFR mutation or ALK rearrangement\n\n          -  No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC\n\n          -  World Health Organization (WHO) Performance Status of 0 or 1\n\n        Exclusion Criteria:\n\n        Patients should not enter the study if any of the following exclusion criteria are\n        fulfilled:\n\n          1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant\n\n          2. Brain metastases or spinal cord compression unless asymptomatic, treated and stable\n             (not requiring steroids)\n\n          3. Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other\n             anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1\n             (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies,\n             excluding therapeutic anticancer vaccines\n\n          4. Active or prior documented autoimmune or inflammatory disorders (including\n             inflammatory bowel disease [eg, colitis or Crohn's disease]
Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or VEGF receptor, or programmed death (PD) 1 or PD-ligand 1/2 signaling pathways.
Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms
Participants with any programmed death-ligand 1 (PD-L1) test result by immunohistochemistry (IHC) are eligible for the study
have not received previous systemic therapy (including investigational agents) targeting programmed cell death protein 1 (PD-1)/ PD-1 ligand (PDL 1) or PD-1/PDL-2 signaling pathways. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anticytotoxic T-lymphocyte-associated antigen-4 antibody, is not permitted
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-1 (anti-PD-L1), anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], tumor necrosis factor receptors OX-40 or CD137) or has participated in prior pembrolizumab (MK-3475) studies
Previous treatment with an anti-programmed cell death 1 [PD1] or programmed cell death ligand 1 [PDL1] inhibitor, including MEDI4736, or an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitory agent
Has received prior therapy with an anti-programmed cell death 1 (PD-1), PD-L1, anti-programmed cell death ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); patients who have previously received MK-3475 or participated in an MK-3475 clinical trial will be ineligible
Patients who have had prior therapy with nivolumab or with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-antigen (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways
Per good clinical practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-programmed death 1 (PD1) therapy should be resolved to less than grade 1
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
Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), anti-programmed cell death-ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Subjects who have had chemotherapy or radiotherapy or any systemic therapy for melanoma within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier; no concomitant therapy is allowed including interleukin-2 (IL2), interferon, ipilimumab, anti-programmed cell death 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) antibody, cytotoxic chemotherapy, immunosuppressive agents, or other investigational therapies
Must provide a tumor sample (archival or newly obtained biopsy) that is adequate for determination of PD (programmed cell death)-Ligand 1 status by immunohistochemistry at a central pathology laboratory prior to enrollment. Note: Adequacy of the tumor sample for PD-Ligand 1 testing is not required prior to enrollment in Part 1C
Prior therapy with an anti-programmed cell death (anti-PD)-1, anti-PD-Ligand 1, anti-PD-Ligand 2 or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab clinical trial. Note: In Part 1C, participants may have received anti-PD-1 and/or anti-Cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) as part of their neo/adjuvant treatment.
Subject whom participated in either arm of the following clinical trials CA209-017, CA209-057, CA209-026, and CA184-104 or received prior treatment with anti-programmed death 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) experimental agents
Histologically- or cytologically-confirmed diagnosis of NSCLC that is anti-programmed cell death ligand 1 (PD-L1) positive per central laboratory review
Systemic cancer therapy (standard or experimental), including cytotoxic chemotherapy or IL-2, received less than 4 weeks or checkpoint blocking agents (e.g., cytotoxic T-lymphocyte protein [CTLA]-4 or programmed cell death protein [PD]1/PD-ligand [L]1 inhibitors) received less than 6 weeks prior to lymphodepletion, with the exception of targeted therapies
Anti-programmed cell death protein-1 (anti-PD-1), PD ligand-1 (PD-L1), PD ligand-2 (PD-L2) agent, an antibody targeting other immuno-regulatory receptors or mechanisms
Previously received pembrolizumab or other anti-programmed cell death-1 (PD-1) or anti-PD-L1 immunotherapy
Received any of the following prescribed medications or therapies in the past: Anti-CD38 antibody, including daratumumab, and/or Anti-PD-1 (programmed death-1) and anti-PD-L1 (programmed death-ligand 1) antibodies
Patients must not have had any prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137 or anti-cytotoxic t-lymphocyte-associated protein 4 ligand (CTLA-4) antibody (or any antibody or drug specifically targeting T-cell costimulation or checkpoint pathways; for questions or uncertainties, please contact the PI or quality assurance manager (QAM)
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
Patients should be excluded if they have had prior treatment with an anti-programmed cell death (PD)1 or anti-PD-ligand (L)1; please contact principal investigator, Devalingam Mahalingam, for specific questions on potential interactions
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-programmed death ligand 2 (PD-L2) agent
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
Has received any previous systemic therapy targeting programmed death (PD) 1 or PD-ligand 1/2 signaling pathways, and other immune checkpoint inhibitors
Received any prior monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1)
Can provide either a newly obtained or archival tumor tissue sample for intratumoral immune-related testing and for anti-programmed cell death (PD-1)
Prior treatment with an anti-programmed cell death (PD)-1, anti-PD-L1 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody
Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 4 weeks prior to the first dose of the study drugs; for oral targeted therapies (such as ibrutinib, idelalisib, venetoclax), a washout of 3 days is allowed; Note: prior treatment with anti cluster of differentiation (CD)20 monoclonal antibody, anti CD52 monoclonal antibody and lenalidomide are allowed; prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death 1 (PD1) therapies is allowed after a wash-out of 5 half-lives
Treatment with an EGFR-TKI within 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; current treatment with potent inhibitors/inducers of cytochrome P450 3A4 (CYP3A4); previous treatment with AZD9291 (or other agents specifically targeted against EGFR T790M mutation positive NSCLC); Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting 1st EGFR TKI treatment; prior exposure to immune-mediated therapy including, but not limited to, other anti cytotoxic T-lymphocyte-associated antigen 4 (anti CTLA-4), anti- programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; major surgery within 4 weeks;
Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti- cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); Note: subjects that received prior therapy with pidilizumab are an exception to this criterion and may qualify for the study
Has received prior therapy with an anti- programmed cell death protein 1 (PD-1), anti- programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-tumor necrosis factor receptor superfamily, member 9 (CD137), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti- programmed cell death ligand 1 (PD-L1), anti- programmed cell death 1 ligand 2 (PD-L2), anti- cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Prior therapy with anti-programmed cell death protein 1 (PD-1), anti-programmed cell death1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Prior treatment with any anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody or anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent, or prior participation in any Merck pembrolizumab clinical trial
Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); previous treatment with sipuleucel-T is permitted
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies
Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies
Prior therapy with anti-programmed cell death protein 1 (PD-1), anti-PD-ligand (L)1, anti-PD-L2, anti-cluster of differentiation (CD)137, anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody therapies, any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, deoxyribonucleic acid (DNA) methyltransferase therapy or histone deacetylase (HDAC) inhibitor therapy
Patients with a history of prior treatment with anti-programmed cell death (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-tumor necrosis factor receptor superfamily, member 9 (CD137), anti-tumor necrosis factor receptor superfamily, member 4 (OX-40), anti- TNF receptor superfamily member 5 (CD40), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies
Prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody
Prior therapy with anti programmed death-1 (anti-PD-1), anti programmed death-ligand 1 (anti-PD-L1) or anti-programmed death-ligand 2 (anti-PD-L2)
Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
Any prior or concurrent investigational or standard therapy for treatment of metastatic NSCLC including radiation therapy, chemotherapy, biological therapy (with the exception of tyrosine kinase inhibitor as a single agent, which must be at least 5 half-lives prior to day 1, and/or immunotherapy, such as a programmed cell death 1 [PD-1] or programmed cell death 1 ligand 1 [PD-L1] inhibitor, which the last dose must have been given at least 4 weeks prior to day 1) or hormonal therapy; (palliative-targeted radiotherapy for brain or bone metastases is permitted providing it has been at least 14 days prior to day 1)
Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death - ligand 1 (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 antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a pembrolizumab (MK-3475) clinical study.
Tissue or Programmed death-ligand 1 (PD-L1) results available Cohort 1A Inclusion Criteria:
Available tumor sample for Programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) and exon 20 T790M testing
Any previous treatment with a programmed cell death protein 1 (PD1) or programmed cell death-1 ligand 1 (PD-L1) inhibitor, including durvalumab
Patients may have received up to two prior therapies including vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) and programmed cell death (PD)-1/PD ligand 1 (L1) inhibitors; prior palliative radiation to metastatic lesion(s) is permitted, provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated
Have had prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, or anticytotoxic T lymphocyte-associated antigen-4 antibody
Subjects may have failed a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) therapy for advanced disease.
For Phase I: For treatment-experienced patients, the following washout periods are required prior to enrollment on the study: 2 weeks wash out after prior local therapy (such as radiation therapy or intra-lesional therapy), 4 weeks wash out after cytotoxic therapy or high dose interleukin-2, and 6 weeks wash out after anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy; for all other therapy not mentioned, a wash out period of at least 5 half-lives will be needed
Has received prior therapy with an anti-PD-1, anti-programmed death-ligand (PD-L)1, or anti-PD-L2 agent
Previous treatment with eribulin mesylate or any anti-programmed death receptor-1 (anti-PD-1), programmed death receptor ligand-1 (PD-L1), or PD-L2 agent.
Prior treatment with any therapy on the programmed cell death 1 (PD-1)/PD-L1 axis or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors unless enrolling the urothelial carcinoma with previous checkpoint inhibition therapy expansion cohort
A history of prior treatment with ipilimumab, nivolumab or other cytotoxic t-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD1) or PD-L1 inhibitor
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
Prior therapy with a Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) or Programmed death- 1\n             (PD-1) antagonist, or Programmed cell death- ligand 1 (PD-L1) or CD137 agonists
Prior treatment with CD137 or OX40 agonists, anti?cytotoxic T-lymphocyte-associated protein (CTLA4), anti?programmed death-1 (PD-1), anti- programmed death-ligand 1 (PD-L1), anti-CD-27, anti- glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents
Prior treatment with immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-programmed cell death 1 (PD-1), and anti-programmed cell death 1 ligand 1 (PD-L1) therapeutic antibodies
Prior immune checkpoint inhibition with anti-PD1/programmed death-ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy or other specific T cell targeting agents
Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2
Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-CD137, Anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) or Anti-Glucocorticoid-induced tumor necrosis factor receptor (anti-GITR). However, Anti-Programmed Death-1 (anti-PD-1), Anti-Programmed Death-Ligand1 (anti-PD-L1) are permissible as prior therapy
Prior use of ipilimumab, other cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking therapies, anti-programmed cell death 1 (PD 1) antibody, cluster of differentiation (CD) 137 agonist or other immune activating therapy such as anti-CD 40 antibody within the last 3 months of enrollment in the study; if any of these of these agents were used more than 3 months earlier to enrollment in study, the patient should have recovered from all toxicity and at least 3 months had passed since last use to allow for clearance and observation of any other side effects from the previous therapy
Patients with a history of prior treatment with an anti-programmed cell death (PD) 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have intervened since the therapy; patients who have received prior vaccine therapy are eligible
Prior treatment with a CD137 agonist, ipilimumab, or the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, or programmed death-1 (PD-1)/programmed cell death 1 ligand 1 (PDL-1) inhibitor
Backfill cohort enrollment may be limited to participants whose tumors have PD-L1 (programmed death-ligand 1) and/or different levels of cluster of differentiation 8 (CD8) expression, as defined by the Sponsor
Backfill enrollment in Phase Ib may be managed such that approximately half of the patients in each backfill cohort will not have been trated with prior immune checkpoint inhibitors (anti-PD-L1/PD-1 [programmed death-1] and/or cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), except for those patients with tumor indications where cancer immunotherapy (CIT) is approved as treatment by local regulatory authorities Additional Inclusion Criteria for Participants in Each Indication-Specific Exploration/Expansion Cohort of Phase 1b:
Prior treatment with anti-programmed death 1 (anti-PD-1)/Programmed cell death 1 ligand 1 (PD-L1) or anti-CD137
Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment with one line of cytotoxic chemotherapy is permitted; prior treatment with targeted therapy (such as ipilimumab, anti-programmed cell death 1 [PD1] and BRAF inhibitor) is permitted
Subjects who received other anti Cytotoxic T-lymphocytic antigen (CTLA-4) (non-ipilimumab) or other anti-Programmed death-1 (PD-1) (non-nivolumab) treatment
Documentation of program death ligand-1 (PD-L1) status prior to randomization.
Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 4 weeks prior to the first dose of the study drugs; for oral targeted therapies (such as ibrutinib, idelalisib, venetoclax), a washout of 3 days is allowed; Note: prior treatment with anti-cluster of differentiation (CD)20 monoclonal antibody, anti-CD52 monoclonal antibody and lenalidomide are allowed; prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death (PD)1 therapies is allowed after a wash-out of 5 half-lives
Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibody
Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-cluster of differentiation (CD)137; or other medicines specifically targeting T cells are prohibited; prior therapy with Bacillus Calmette-Guerin (BCG) is permitted; prior interleukin (IL)-2 is permitted
Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period
Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed cell death 1/ anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated protein 4) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event
Prior treatment with any anti-Programmed Death (PD)-1, or PD-L1 or PD-L2 agent; or with azacitidine (any formulation) or any other hypomethylating agent; or with anti-cytoplasmic (CD) 137, or anti-cytotoxic T-Lymphocyte Associated Protein (CTLA)-4 antibody (including ipilimumab) or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents or inhibitors of checkpoint pathways, such as anti- programmed cell death protein 1 (PD-1), anti- programmed cell death 1 ligand 1 (PD-L1), anti- programmed cell death 1 ligand 2 (PD-L2), anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells are prohibited. However, for dose escalation, prior treatment with the marketed inhibitors of the immune checkpoint pathway, such as nivolumab and pembrolizumab, is allowed. In addition, in each of the expansion cohorts, 6 response-evaluable participants with prior exposure to anti-PD-1 or anti-PD-L1 agents will be allowed to enroll.
Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T cell receptor (such as cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in Merck pembrolizumab (MK-3475) clinical studies.
Have received prior treatment with an anti PD-1, anti-programmed death ligand 1 (PD-L1), or anti cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agent.