A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)

Phase 1

Terminated

Conditions: Advanced Cancer

Interventions: Drug: Avelumab
Drug: PF-04518600
Drug: PD 0360324
Drug: Utomilumab
Drug: CMP-001

Registration Number: NCT02554812

Lead Sponsor: Pfizer

Brief Summary: This is a Phase 1b/2 dose-optimization study to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of avelumab (MSB0010718C) in combination with other cancer immunotherapies in patients with locally advanced or metastatic solid tumors. The primary purpose is to assess the safety and early signs of efficacy of various avelumab combinations with other cancer immunotherapies, optimizing dosing regimens as appropriate, in a limited series of indications.

Detailed Description: This is a Phase 1b/2, open-label, multi-center, multiple-dose, safety, clinical activity, PK, and PD study of avelumab in combination with other immune modulators in adult patients with locally advanced or metastatic solid tumors (eg, non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), gastric cancer, platinum resistant ovarian cancer, bladder cancer, small cell lung cancer (SCLC) and progressing tenosynovial giant cell tumor/pigmented villonodular synovitis (TGCT/PVNS) . In Phase 1b, this includes patients whose disease has progressed on standard of care therapy or for whom no standard therapy is available. In Phase 2, enrollment criteria regarding prior treatment(s) received varies by tumor type. Incorporation of the other immune modulators into this study is based on preclinical and clinical data supportive of single-agent tolerability and potential clinical benefit, as well as non-clinical data suggesting safety, tolerability and clinical benefit of the agent(s) in combination with avelumab. Combinations of avelumab plus other immune modulator(s) to be evaluated are as follows:

* Combination A: avelumab plus utomilumab (4-1BB agonist mAb)

* Combination B: avelumab plus PF-04518600 (OX40 agonist mAb)

* Combination C: avelumab plus PD 0360324 (M-CSF mAb)

* Combination D: avelumab plus utomilumab plus PF-04518600

* Combination F: avelumab plus CMP-001 (TLR9 agonist) and avelumab plus CMP-001 plus utomilumab and avelumab plus CMP-001 and PF-04518600 Each combination will be studied individually in 2 study parts: 1) a Phase 1b Lead-in part to evaluate safety, and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and RP2D (if applicable), of the combination, and 2) a Phase 2 part to evaluate efficacy and further evaluate safety of the selected dose from the Phase 1b portion in pre-specified patient populations.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 409

Inclusion Criteria

Histological or cytological diagnosis of advanced/metastatic solid tumor. Measurable disease by RECIST 1.1 with at least 1 measurable lesion that has not been previously irradiated. Availability of tumor specimen taken within 1 year prior to study entry, with no intervening systemic anti-cancer therapy. No prior PD-1/PDL-1 therapy allowed. Combination A: Phase 1b, patients with NSCLC that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, SCCHN, TNBC in any line of therapy, SCLC, 1st line NSCLC. 1st line NSCLC must demonstrate to express PD-L1. Activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination B: Phase 1b, patients with advanced solid tumors (NSCLC, SCCHN, melanoma) that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, or SCCHN. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. Activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination C: Ovarian cancer, SCCHN, NSCLC, gastric cancer, platinum resistant ovarian cancer. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. TGCT/PVNS that is either inoperable or requires extensive resection. Prior treatment with agents targeting CSF-1/CSF-1R not allowed. NSCLC activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination D: NSCLC, melanoma, SCCHN, bladder cancer. NSCLC activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. Combination F: Recurrent or metastatic SCCHN. One to three prior lines of systemic therapy for advanced stage or metastatic disease. Patients must have received anti PD-1/PD-L1 containing therapy (requires at least two doses of PD-1/PD-L1 agent).Disease progression no earlier than 6 weeks from initiation of the latest anticancer therapy. Evidence of radiologic progression is required. • Patient must be a candidate for intralesional administration with at least one tumor lesion which can be injected safely.
ECOG performance status 0 or 1
Estimated life expectancy of at least 3 months
Adequate bone marrow, renal, and liver function
Resolved acute effects of prior therapy
Negative serum pregnancy test at screening
Male and female patients able to have children must agree to use at least 1 highly effective method of contraception throughout the study and for at least 90 days after last dose
Signed and dated informed consent

Exclusion Criteria

Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry. Combination F:PD-1/PD-L1 agent within 14 days prior study entry.
Current or prior use of immunosuppressive medication within 7 days prior to study entry
Active autoimmune disease requiring systemic steroids or immunosuppressive agents within 7 days prior to study entry
Known prior or suspected hypersensitivity to investigational products
Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry
Patients with known symptomatic brain metastases requiring steroids
Previous high-dose chemotherapy requiring stem cell rescue
Prior allogeneic stem cell transplant or organ graft
Any of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
Symptomatic pulmonary embolism within 6 months prior to study entry
Known HIV or AIDS-related illness
Active infection requiring systemic therapy
Positive HBV or HCV test indicating acute or chronic infection
Administration of a live vaccine within 4 weeks prior to study entry
Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason ≤6) prostate cancer
Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
Persisting toxicity related to prior therapy >Grade 1
Other severe acute or chronic medical condition
Combo C :Existing periorbital edema.
Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture (within 12 weeks prior study entry)

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Combination D Dose expansion cohorts	Avelumab	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Combination B Expansion Cohorts	PF-04518600	PF-04518600 + avelumab in selected tumor types
Combination C Dose expansion cohorts	PD 0360324	PD 0360324 + aveluamb in selected tumor types
Cohort A1	Utomilumab	NSCLC patients treated with avelumab + utomilumab (Dose level 1)
Combination C Dose escalation cohorts	PD 0360324	PD 0360324 + avelumab in selected tumor types
Cohort F3	PF-04518600	CMP-001 +avelumab+PF-04518600 in SCCHN
Cohort F3	CMP-001	CMP-001 +avelumab+PF-04518600 in SCCHN
Combination D Dose escalation cohorts	PF-04518600	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Cohort F2	CMP-001	CMP-001+avelumab+utomilumab in SCCHN
Combination D Dose expansion cohorts	PF-04518600	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Combination B Dose Escalation	PF-04518600	PF-04518600 + avelumab in selected tumor types
Cohort F1	CMP-001	CMP-001 +avelumab in SCCHN
Cohort A8	Utomilumab	NSCLC first-line Stage IV treated with avelumab +PF-05082566
Cohort A2	Avelumab	NSCLC patients treated with avelumab + utomilumab (Dose level 2)
Cohort A2	Utomilumab	NSCLC patients treated with avelumab + utomilumab (Dose level 2)
Cohort A1	Avelumab	NSCLC patients treated with avelumab + utomilumab (Dose level 1)
Cohort A3	Avelumab	NSCLC patients treated with avelumab + utomilumab (Dose level 3)
Cohort A4	Avelumab	Melanoma patients treated with avelumab +utomilumab
Cohort A3	Utomilumab	NSCLC patients treated with avelumab + utomilumab (Dose level 3)
Cohort A4	Utomilumab	Melanoma patients treated with avelumab +utomilumab
Cohort A5	Avelumab	SCCHN patients treated with avelumab + utomilumab
Cohort A5	Utomilumab	SCCHN patients treated with avelumab + utomilumab
Combination B Expansion Cohorts	Avelumab	PF-04518600 + avelumab in selected tumor types
Cohort A6	Avelumab	TNBC patients treated with avelumab + utomilumab
Cohort A6	Utomilumab	TNBC patients treated with avelumab + utomilumab
Cohort A7	Avelumab	SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
Cohort A7	Utomilumab	SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
Cohort A8	Avelumab	NSCLC first-line Stage IV treated with avelumab +PF-05082566
Combination B Dose Escalation	Avelumab	PF-04518600 + avelumab in selected tumor types
Combination C Dose expansion cohorts	Avelumab	PD 0360324 + aveluamb in selected tumor types
Combination C Dose escalation cohorts	Avelumab	PD 0360324 + avelumab in selected tumor types
Combination D Dose escalation cohorts	Avelumab	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Combination D Dose escalation cohorts	Utomilumab	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Combination D Dose expansion cohorts	Utomilumab	PF-05082566 + PF-04518600 + avelumab in selected tumor types
Cohort A9	Avelumab	NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
Cohort A9	Utomilumab	NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
Cohort A10	Avelumab	NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
Cohort A10	Utomilumab	NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
Cohort F1	Avelumab	CMP-001 +avelumab in SCCHN
Cohort F2	Avelumab	CMP-001+avelumab+utomilumab in SCCHN
Cohort F3	Avelumab	CMP-001 +avelumab+PF-04518600 in SCCHN
Cohort F2	Utomilumab	CMP-001+avelumab+utomilumab in SCCHN

Primary Outcome Measures

Name	Time	Method
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment for Combination A	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 53 months approximately)	OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
Phase 1b Lead-in: Number of Participants With First 2 Cycles Dose Limiting Toxicity (DLT) for Combination A	Baseline up to Cycle 2 (up to 8 weeks)	Severity of AEs graded as per CTCAE v4.03. Phase 1b lead-in, AEs occurring during DLT observation period, that attributable to one or more study drug in combination was classified as DLT: Hematologic: Grade (G)4 neutropenia lasting \>7 day; Febrile neutropenia; Neutropenic infection; G \>=3 thrombocytopenia with bleeding; G4 thrombocytopenia; G4 anemia. Non-Hematologic (Non-Laboratory): Any G3 toxicity, except following: Transient (24 H) G3 fatigue, local reaction, or headache that resolved to G1; G3-4 nausea/vomiting controlled by medical therapy within 72H; G3 hypertension controlled by medical therapy; G3 diarrhea improved to G \<=2 within 72H after medical therapy; G3 skin toxicity resolved to G \<=1 in \<7 days after medical management; G \>=3 amylase or lipase abnormality not associated with pancreatitis;G3 endocrinopathies controlled with medical therapy; Tumor flare phenomenon.G4 or G3 CRS lasting \>24 H despite treatment.
Phase 1b Lead-in: Number of Participants With First Cycle DLT for Combination F	Baseline up to first Cycle (up to 4 weeks)	Severity of AEs graded as per CTCAE v4.03. Phase 1b lead-in, AEs occurring during DLT observation period, that attributable to one or more study drug in combination was classified as DLT: Hematologic: Grade (G)4 neutropenia lasting \>7 day; Febrile neutropenia; Neutropenic infection; G \>=3 thrombocytopenia with bleeding; G4 thrombocytopenia; G4 anemia. Non-Hematologic (Non-Laboratory): Any G3 toxicity, except following: Transient (24 H) G3 fatigue, local reaction, or headache that resolved to G1; G3-4 nausea/vomiting controlled by medical therapy within 72H; G3 hypertension controlled by medical therapy; G3 diarrhea improved to G \<=2 within 72H after medical therapy; G3 skin toxicity resolved to G \<=1 in \<7 days after medical management; G \>=3 amylase or lipase abnormality not associated with pancreatitis;G3 endocrinopathies controlled with medical therapy; Tumor flare phenomenon.G4 or G3 CRS lasting \>24 H despite treatment.
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination B	Baseline up to Cycle 2 (up to 8 weeks)	Severity of AEs graded as per CTCAE v4.03. Phase 1b lead-in, AEs occurring during DLT observation period, that attributable to one or more study drug in combination was classified as DLT: Hematologic: Grade (G)4 neutropenia lasting \>7 day; Febrile neutropenia; Neutropenic infection; G \>=3 thrombocytopenia with bleeding; G4 thrombocytopenia; G4 anemia. Non-Hematologic (Non-Laboratory): Any G3 toxicity, except following: Transient (24 H) G3 fatigue, local reaction, or headache that resolved to G1; G3-4 nausea/vomiting controlled by medical therapy within 72H; G3 hypertension controlled by medical therapy; G3 diarrhea improved to G \<=2 within 72H after medical therapy; G3 skin toxicity resolved to G \<=1 in \<7 days after medical management; G \>=3 amylase or lipase abnormality not associated with pancreatitis;G3 endocrinopathies controlled with medical therapy; Tumor flare phenomenon.G4 or G3 CRS lasting \>24 H despite treatment.
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination C	Baseline up to Cycle 2 (up to 8 weeks)	Severity of AEs graded as per CTCAE v4.03. Phase 1b lead-in, AEs occurring during DLT observation period, that attributable to one or more study drug in combination was classified as DLT: Hematologic: Grade (G)4 neutropenia lasting \>7 day; Febrile neutropenia; Neutropenic infection; G \>=3 thrombocytopenia with bleeding; G4 thrombocytopenia; G4 anemia. Non-Hematologic (Non-Laboratory): Any G3 toxicity, except following: Transient (24 H) G3 fatigue, local reaction, or headache that resolved to G1; G3-4 nausea/vomiting controlled by medical therapy within 72H; G3 hypertension controlled by medical therapy; G3 diarrhea improved to G \<=2 within 72H after medical therapy; G3 skin toxicity resolved to G \<=1 in \<7 days after medical management; G \>=3 amylase or lipase abnormality not associated with pancreatitis;G3 endocrinopathies controlled with medical therapy; Tumor flare phenomenon.G4 or G3 CRS lasting \>24 H despite treatment.
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination D	Baseline up to Cycle 2 (up to 8 weeks)	Severity of AEs graded as per CTCAE v4.03. Phase 1b lead-in, AEs occurring during DLT observation period, that attributable to one or more study drug in combination was classified as DLT: Hematologic: Grade (G)4 neutropenia lasting \>7 day; Febrile neutropenia; Neutropenic infection; G \>=3 thrombocytopenia with bleeding; G4 thrombocytopenia; G4 anemia. Non-Hematologic (Non-Laboratory): Any G3 toxicity, except following: Transient (24 H) G3 fatigue, local reaction, or headache that resolved to G1; G3-4 nausea/vomiting controlled by medical therapy within 72H; G3 hypertension controlled by medical therapy; G3 diarrhea improved to G \<=2 within 72H after medical therapy; G3 skin toxicity resolved to G \<=1 in \<7 days after medical management; G \>=3 amylase or lipase abnormality not associated with pancreatitis;G3 endocrinopathies controlled with medical therapy; Tumor flare phenomenon.G4 or G3 CRS lasting \>24 H despite treatment.
Phase 2: Percentage of Participants With Confirmed OR as Per RECIST v 1.1 by Investigator Assessment for Combination B	From start of the treatment until disease progression or death due to any cause, whichever occurred first (approximately 26 months)	OR: CR or PR determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of PD, confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures \<10 mm. PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm, appearance of one or more new lesions was considered PD.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination A	Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 6.5 years)	TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per National Cancer Institute (NCI) CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination B	Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 3.5 years)	TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per NCI CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3: Combination A	Baseline up to end of treatment/withdrawal (maximum of 6.5 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening hematology laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Anemia, lymphocyte count decreased, Platelet count decreased, neutrophil count decreased, and white blood cell decreased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination F	Baseline up to end of treatment/withdrawal (maximum of 3 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening hematology laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Anemia, lymphocyte count decreased, Platelet count decreased, neutrophil count decreased, and white blood cell decreased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination A	Baseline up to end of treatment/withdrawal (maximum of 6.5 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening chemistry laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hyperglycemia, lipase increased and serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination C	Baseline up to end of treatment/withdrawal (maximum of 1.8 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening hematology laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Anemia, lymphocyte count decreased, Platelet count decreased, neutrophil count decreased, and white blood cell decreased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination A	1-hour post-infusion (at end of infusion) on Day 1 of Cycle 1,3,5,8,12; Day 8 of Cycle 1 (non-dosing). For ''Phase 2 1L NSCLC: Avelumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycle 3,5,8,12	Cmax is maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Avelumab and PF-04518600 in Combination B	1-hour post-dose on Day 1,15 of Cycle 1; Day 8 of Cycle 1 (non-dosing); Day 1 of Cycle 2, 4, 6 and Cycle 10	Cmax is maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination F	1-hour post-infusion (i.e. at the end of infusion) on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10	Cmax is maximum observed plasma concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination D	Pre-dose on Day 1 of Cycle 1, 2, 4, 6 and Cycle 10; Day 15 of Cycle 1 (non-dosing)	Ctrough is steady-state pre-dose concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination D	Pre-dose on Day 1 of Cycle 1, 3, 5, 8 and Cycle 12; Day 15 of Cycle 1 (non-dosing)	Ctrough is steady-state pre-dose concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination F	Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2 and 4	Ctrough is steady-state pre-dose concentration.
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination C	Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 1.8 years)	TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per NCI CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination A	1-hour post-dose (at end of infusion) on Day 1,15 of Cycle 1; Day 8 of Cycle 1 (non-dosing); Day 1 of Cycle 2, 4, 6, 10. For ''Phase 2 1L NSCLC: Utomilumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycle 2, 4, 6, 10	Cmax is maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination D	1 hour post-dose (at end of infusion) on Days 1 and 15 of Cycle 1; Day 8 of Cycle 1 (non-dosing); Pre-dose and 1 hour post-dose on Day 1 of Cycle 2, 4, 6, 10	Cmax is maximum observed plasma concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination A	Pre-dose on Day 1 of Cycles 1,3,5,8, and Cycle 12; Day 15 of Cycle 1 (non-dosing). For ''Phase 2 1L NSCLC: Avelumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycles 3,5,8 and 12	Ctrough is steady-state pre-dose concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PF-04518600 in Combination B	Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10	Ctrough is steady-state pre-dose concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination D	Pre-dose on Day 1 and 15 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2, 4, 6 and Cycle 10	Ctrough is steady-state pre-dose concentration.
Number of Participants With Positive ADA Levels For Combination B	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination D	Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 4.3 years)	TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per NCI CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination F	Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 3 years)	TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per NCI CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination B	Baseline up to end of treatment/withdrawal (maximum of 3.5 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening chemistry laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hyperglycemia, lipase increased and serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination C	Baseline up to end of treatment/withdrawal (maximum of 1.8 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening chemistry laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hyperglycemia, lipase increased and serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination B	Baseline up to end of treatment/withdrawal (maximum of 3.5 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening hematology laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Anemia, lymphocyte count decreased, Platelet count decreased, neutrophil count decreased, and white blood cell decreased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination D	Baseline up to end of treatment/withdrawal (maximum of 4.3 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening hematology laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Anemia, lymphocyte count decreased, Platelet count decreased, neutrophil count decreased, and white blood cell decreased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination F	Baseline up to end of treatment/withdrawal (maximum of 3 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening chemistry laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hyperglycemia, lipase increased and serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Maximum Observed Plasma Concentration (Cmax) of Avelumab and PD 0360324 in Combination C	1 hour (i.e. at the end of infusion) post-dose on Day 1,15 of Cycle 1; Day 8 of Cycle 1 (non-dosing); Day 1 of Cycle 2, 4, 6 and Cycle 10	Cmax is maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination D	1 hour (at end of infusion) post-dose on Day 1 of Cycles 1, 3, 5, 8 and Cycle 12; Days 8 of Cycle 1 (non-dosing)	Cmax is maximum observed plasma concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PD 0360324 in Combination C	Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10	Ctrough is steady-state pre-dose concentration.
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination D	Baseline up to end of treatment/withdrawal (maximum of 4.3 years)	The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants with new abnormal or worsening chemistry laboratory test is presented." Participants with any grade \>=3 is presented for following parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hyperglycemia, lipase increased and serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Maximum Observed Plasma Concentration (Cmax) of PF-04518600 in Combination D	1 hour post-infusion (at end of infusion) on Day 1 and 15 of Cycle 1; Day 8 of Cycle 1 (non-dosing); Day 1 of Cycle 2, 4, 6 and Cycle 10	Cmax is maximum observed plasma concentration.
Number of Participants With Positive ADA Levels Against Avelumab and PF-04518600 For Combination F	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
Time to Tumor Response (TTR) for Combination A	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)	TTR was defined, for participants with an objective response (confirmed CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
TTR for Combination B	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)	TTR was defined, for participants with an objective response (confirmed CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
TTR for Combination C	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)	TTR was defined, for participants with an objective response (confirmed CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination A	Pre-dose on Days 1 and 15 of Cycle 1, Day 8 of Cycle 1 (non-dosing) and then Day 1 of Cycles 2,4,6 and Cycle 10. For ''Phase 2 1L NSCLC: Utomilumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycles 2,4,6,10	Ctrough is steady-state pre-dose concentration.
DR for Combination B	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of \>=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after \>=2 missing tumor assessments.
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination F	Pre-dose on Day 1 and 15 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2, 4, 6 and Cycle 10	Ctrough is steady-state pre-dose concentration.
Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination F	Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycles 2 and 4	Ctrough is steady-state pre-dose concentration.
Number of Participants With Positive ADA Levels Against Utomilumab For Combination A	Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12. For ''Phase 2 1L NSCLC: Avelumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycle 3, 5, 8, 12	ADA ever-positive was defined as at least one positive ADA result at any time point.
Number of Participants With Positive ADA Levels For Combination C	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
Number of Participants With Positive ADA Levels Against Avelumab and PF-04518600 For Combination D	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
Number of Participants With Positive ADA Levels Against Utomilumab For Combination F	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
DR for Combination D	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of \>=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after \>=2 missing tumor assessments.
DR for Combination F	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of \>=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after \>=2 missing tumor assessments.
Number of Participants With Positive Anti-Drug Antibody (ADA) Against Avelumab For Combination A	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, 10. For ''Phase 2 1L NSCLC: Utomilumab then Utomilumab + Avelumab'' reporting group: Day 1 of Cycle 2, 4, 6, 10	ADA ever-positive was defined as at least one positive ADA result at any time point.
Number of Participants With Positive ADA Levels Against Utomilumab For Combination D	Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12	ADA ever-positive was defined as at least one positive ADA result at any time point.
TTR for Combination F	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)	TTR was defined, for participants with an objective response (confirmed CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
Duration of Response (DR) for Combination A	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of \>=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after \>=2 missing tumor assessments.
PFS for Combination D	From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of \>=5 mm, or appearance of \>=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after \>=2 missing tumor assessments.
TTR for Combination D	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)	TTR was defined, for participants with an objective response (confirmed CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
PFS for Combination B	From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of \>=5 mm, or appearance of \>=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after \>=2 missing tumor assessments.
PFS for Combination C	From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of \>=5 mm, or appearance of \>=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after \>=2 missing tumor assessments.
OS for Combination C	From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination B	Baseline (Day 1)	PD-L1 protein expression is determined by using TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen is considered to have PD-L1 expression if TPS \>=1% and high PD-L1 expression if TPS \>= 50%. Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as \>=1% and negative is defined as \<1%.
DR for Combination C	From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to \<10 mm. PR: \>= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of \>=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after \>=2 missing tumor assessments.
PFS for Combination F	From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of \>=5 mm, or appearance of \>=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after \>=2 missing tumor assessments.
OS for Combination F	From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination A	From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)	OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as \>=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination B	From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)	OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of CR or PR, were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as \>=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination C	From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)	OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of CR or PR, were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as \>=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free Survival (PFS) for Combination A	From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of \>=5 mm, or appearance of \>=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after \>=2 missing tumor assessments.
Overall Survival (OS) for Combination A	From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
OS for Combination B	From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination F	From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)	OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of CR or PR, were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as \>=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating Cluster of Differentiation 8 (CD8+) Lymphocytes at Baseline for Combination A	Baseline (Day 1)	PD-L1 protein expression is determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen is considered to have PD-L1 expression if TPS \>=1% and high PD-L1 expression if TPS \>= 50%. Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as \>=1% and negative is defined as \<1%.
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination C	Baseline (Day 1)	PD-L1 protein expression is determined by using TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen is considered to have PD-L1 expression if TPS \>=1% and high PD-L1 expression if TPS \>= 50%. Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as \>=1% and negative is defined as \<1%.
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination F	Baseline (Day 1)	PD-L1 protein expression is determined by using TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen is considered to have PD-L1 expression if TPS \>=1% and high PD-L1 expression if TPS \>= 50%. Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as \>=1% and negative is defined as \<1%.
OS for Combination D	From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 7.3 years)	OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination D	From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)	OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of CR or PR, were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as \>=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination D	Baseline (Day 1)	PD-L1 protein expression is determined by using TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen is considered to have PD-L1 expression if TPS \>=1% and high PD-L1 expression if TPS \>= 50%. Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as \>=1% and negative is defined as \<1%.

Trial Locations

Locations (83): Florida Cancer Specialists
🇺🇸
Sarasota, Florida, United States
The Mater Hospital
🇦🇺
North Sydney, New South Wales, Australia
Mount Sinai Comprehensive Cancer Center - Aventura
🇺🇸
Aventura, Florida, United States
UCLA Hematology-Oncology Infusion Center
🇺🇸
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸
Los Angeles, California, United States
UCLA Clinical Research Unit (Adminstration Office)
🇺🇸
Los Angeles, California, United States
UPMC Shadyside Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
UPCI Investigational Drug Service
🇺🇸
Pittsburgh, Pennsylvania, United States
UC San Diego Medical Center - Hillcrest
🇺🇸
San Diego, California, United States
Vanderbilt University Oncology Pharmacy
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncology, PLLC
🇺🇸
Nashville, Tennessee, United States
Henry-Joyce Cancer Clinic
🇺🇸
Nashville, Tennessee, United States
University of Michigan Hospitals
🇺🇸
Ann Arbor, Michigan, United States
Sanford Research
🇺🇸
Sioux Falls, South Dakota, United States
National Cancer Center Hospital
🇯🇵
Chuo-ku, Tokyo, Japan
Cabrini Hospital Malvern
🇦🇺
Malvern, Victoria, Australia
The Sarah Cannon Research Institute / Tennessee Oncology, PLLC
🇺🇸
Nashville, Tennessee, United States
PH 145294, Centre Hospitalier de l'Universite de Montreal (CHUM), Oncology Research Pharmacy
🇨🇦
Montreal, Quebec, Canada
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Sanford Gynecologic Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Karmanos Cancer Institute Weisberg Cancer Treatment Center
🇺🇸
Farmington Hills, Michigan, United States
NYU Langone Medical Center
🇺🇸
New York, New York, United States
Sanford Cancer Center Oncology Clinic & Pharmacy
🇺🇸
Sioux Falls, South Dakota, United States
Investigational Pharmacy, Karmanos Cancer Center
🇺🇸
Detroit, Michigan, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Weill Cornell Medical College
🇺🇸
New York, New York, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Koman Family Outpatient Pavilion
🇺🇸
La Jolla, California, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
🇺🇸
La Jolla, California, United States
UCSD Medical Center - Encinitas
🇺🇸
Encinitas, California, United States
UC San Diego Perlman Medical Offices
🇺🇸
La Jolla, California, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
UCLA Hematology-Oncology Clinic
🇺🇸
Los Angeles, California, United States
UCSD Medical Center - Vista
🇺🇸
Vista, California, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸
Miami Beach, Florida, United States
H Lee Moffitt Cancer Center and Research Institute
🇺🇸
Tampa, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
NYU Investigational Pharmacy
🇺🇸
New York, New York, United States
VA NY Harbor Healthcare System
🇺🇸
New York, New York, United States
NYU Laura and Isaac Perlmutter Cancer Center
🇺🇸
New York, New York, United States
Weill Cornell Medical College/New York Presbyterian Hospital
🇺🇸
New York, New York, United States
Research Pharmacy #PH#
🇺🇸
New York, New York, United States
Southeastern Medical Oncology Center
🇺🇸
Jacksonville, North Carolina, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
Sampson Regional Medical Center
🇺🇸
Clinton, North Carolina, United States
Onslow Memorial Hospital
🇺🇸
Jacksonville, North Carolina, United States
University of Pittsburgh Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
Sanford Interventional Radiology
🇺🇸
Sioux Falls, South Dakota, United States
Sanford ENT Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Sanford USD Medical Center
🇺🇸
Sioux Falls, South Dakota, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
The Royal Marsden Hospital
🇬🇧
London, United Kingdom
UT Southwestern Simmons Comprehensive Cancer Center
🇺🇸
Dallas, Texas, United States
Macquarie University
🇦🇺
Macquarie University, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺
Camperdown, New South Wales, Australia
Brighton Medical Imaging
🇦🇺
Brighton, Victoria, Australia
Melanoma Institute Australia
🇦🇺
North Sydney, New South Wales, Australia
Baxter Healthcare
🇦🇺
Old Toongabie, New South Wales, Australia
Austin Health
🇦🇺
Heidelberg, Victoria, Australia
Cabrini Hospital Brighton
🇦🇺
Brighton, Victoria, Australia
Cabrini Hospital
🇦🇺
Malvern, Victoria, Australia
Malvern Medical Imaging
🇦🇺
Malvern, Victoria, Australia
Macquarie Heart
🇦🇺
New South Wales, Australia
The Ottawa Hospital Cancer Centre
🇨🇦
Ottawa, Ontario, Canada
British Columbia Cancer Agency - Vancouver Centre
🇨🇦
Vancouver, British Columbia, Canada
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦
Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal (CHUM)
🇨🇦
Montreal, Quebec, Canada
Institut Gustave Roussy
🇫🇷
Villejuif, France
National Cancer Center Hospital East
🇯🇵
Kashiwa, Chiba, Japan
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
🇵🇱
Warszawa, Poland
Investigational Drug Services, National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
The Royal Marsden NHS Foundation Trust
🇬🇧
London, United Kingdom
Sarah Cannon Research Institute UK
🇬🇧
London, United Kingdom
The Harley Street Clinic
🇬🇧
London, United Kingdom
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States