A PHASE 1B/2 OPEN-LABEL STUDY TO EVALUATE SAFETY, CLINICAL ACTIVITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH OTHER CANCER IMMUNOTHERAPIES IN PATIENTS WITH ADVANCED MALIGNANCIES
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 409
- 试验地点
- 83
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-L
- •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
排除标准
- •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)
研究组 & 干预措施
Cohort A1
NSCLC patients treated with avelumab + utomilumab (Dose level 1)
干预措施: Avelumab (Drug)
Cohort A1
NSCLC patients treated with avelumab + utomilumab (Dose level 1)
干预措施: Utomilumab (Drug)
Cohort A2
NSCLC patients treated with avelumab + utomilumab (Dose level 2)
干预措施: Avelumab (Drug)
Cohort A2
NSCLC patients treated with avelumab + utomilumab (Dose level 2)
干预措施: Utomilumab (Drug)
Cohort A3
NSCLC patients treated with avelumab + utomilumab (Dose level 3)
干预措施: Avelumab (Drug)
Cohort A3
NSCLC patients treated with avelumab + utomilumab (Dose level 3)
干预措施: Utomilumab (Drug)
Cohort A4
Melanoma patients treated with avelumab +utomilumab
干预措施: Avelumab (Drug)
Cohort A4
Melanoma patients treated with avelumab +utomilumab
干预措施: Utomilumab (Drug)
Cohort A5
SCCHN patients treated with avelumab + utomilumab
干预措施: Avelumab (Drug)
Cohort A5
SCCHN patients treated with avelumab + utomilumab
干预措施: Utomilumab (Drug)
Cohort A6
TNBC patients treated with avelumab + utomilumab
干预措施: Avelumab (Drug)
Cohort A6
TNBC patients treated with avelumab + utomilumab
干预措施: Utomilumab (Drug)
Cohort A7
SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
干预措施: Avelumab (Drug)
Cohort A7
SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
干预措施: Utomilumab (Drug)
Cohort A8
NSCLC first-line Stage IV treated with avelumab +PF-05082566
干预措施: Avelumab (Drug)
Cohort A8
NSCLC first-line Stage IV treated with avelumab +PF-05082566
干预措施: Utomilumab (Drug)
Combination B Dose Escalation
PF-04518600 + avelumab in selected tumor types
干预措施: Avelumab (Drug)
Combination B Dose Escalation
PF-04518600 + avelumab in selected tumor types
干预措施: PF-04518600 (Drug)
Combination B Expansion Cohorts
PF-04518600 + avelumab in selected tumor types
干预措施: Avelumab (Drug)
Combination B Expansion Cohorts
PF-04518600 + avelumab in selected tumor types
干预措施: PF-04518600 (Drug)
Combination C Dose escalation cohorts
PD 0360324 + avelumab in selected tumor types
干预措施: Avelumab (Drug)
Combination C Dose escalation cohorts
PD 0360324 + avelumab in selected tumor types
干预措施: PD 0360324 (Drug)
Combination C Dose expansion cohorts
PD 0360324 + aveluamb in selected tumor types
干预措施: Avelumab (Drug)
Combination C Dose expansion cohorts
PD 0360324 + aveluamb in selected tumor types
干预措施: PD 0360324 (Drug)
Combination D Dose escalation cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: Avelumab (Drug)
Combination D Dose escalation cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: Utomilumab (Drug)
Combination D Dose escalation cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: PF-04518600 (Drug)
Combination D Dose expansion cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: Avelumab (Drug)
Combination D Dose expansion cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: Utomilumab (Drug)
Combination D Dose expansion cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
干预措施: PF-04518600 (Drug)
Cohort A9
NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
干预措施: Avelumab (Drug)
Cohort A9
NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
干预措施: Utomilumab (Drug)
Cohort A10
NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
干预措施: Avelumab (Drug)
Cohort A10
NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
干预措施: Utomilumab (Drug)
Cohort F1
CMP-001 +avelumab in SCCHN
干预措施: Avelumab (Drug)
Cohort F1
CMP-001 +avelumab in SCCHN
干预措施: CMP-001 (Drug)
Cohort F2
CMP-001+avelumab+utomilumab in SCCHN
干预措施: Avelumab (Drug)
Cohort F2
CMP-001+avelumab+utomilumab in SCCHN
干预措施: Utomilumab (Drug)
Cohort F2
CMP-001+avelumab+utomilumab in SCCHN
干预措施: CMP-001 (Drug)
Cohort F3
CMP-001 +avelumab+PF-04518600 in SCCHN
干预措施: Avelumab (Drug)
Cohort F3
CMP-001 +avelumab+PF-04518600 in SCCHN
干预措施: PF-04518600 (Drug)
Cohort F3
CMP-001 +avelumab+PF-04518600 in SCCHN
干预措施: CMP-001 (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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)
- 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)
- 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)
- 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))
- 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))
- 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)
- 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))
- 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)
- 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)
- 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)
- 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)
- 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)
- Number of Participants With Positive ADA Levels For Combination B(Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10)
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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)
- 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))
- 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)
- 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))
- 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)
- 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)
- 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 for Combination B(From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years))
- TTR for Combination C(From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years))
- 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)
- 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))
- 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)
- 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)
- 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)
- Number of Participants With Positive ADA Levels For Combination C(Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10)
- 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)
- 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)
- 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 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))
- 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)
- Number of Participants With Positive ADA Levels Against Utomilumab For Combination D(Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12)
- TTR for Combination F(From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years))
- 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))
- 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))
- TTR for Combination D(From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years))
- 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 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))