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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Avelumab; Drug: Utomilumab; Drug: PF-04518600; Drug: PD 0360324; Drug: CMP-001

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.

• Study Type: Interventional
• Enrollment (Actual): 409
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales, Australia, 2109
    • Macquarie Heart
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Macquarie University, New South Wales, Australia, 2109
      • Macquarie University
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
    • North Sydney, New South Wales, Australia, 2060
      • The Mater Hospital
    • Old Toongabie, New South Wales, Australia, 2146
      • Baxter Healthcare
  • Victoria
    • Brighton, Victoria, Australia, 3186
      • Cabrini Hospital Brighton
    • Brighton, Victoria, Australia, 3186
      • Brighton Medical Imaging
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Malvern, Victoria, Australia, 3144
      • Malvern Medical Imaging
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montreal, Quebec, Canada, H2X 0C2
      • PH 145294, Centre Hospitalier de l'Universite de Montreal (CHUM), Oncology Research Pharmacy
• France
  • Villejuif, France, 94805
    • Institut Gustave Roussy
  • Cedex
    • Villejuif, Cedex, France, 94805
      • Institut Gustave Roussy
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Poland
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 100
    • Investigational Drug Services, National Taiwan University Hospital
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • London, United Kingdom, W1G 7LJ
    • The Harley Street Clinic
  • London, United Kingdom, W1G 8PP
    • The Harley Street Clinic
• United States
  • California
    • Encinitas, California, United States, 92024
      • UCSD Medical Center - Encinitas
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • La Jolla, California, United States, 92037
      • UC San Diego Perlman Medical Offices
    • La Jolla, California, United States, 92037
      • Koman Family Outpatient Pavilion
    • La Jolla, California, United States, 92037
      • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90024
      • UCLA Clinical Research Unit (Adminstration Office)
    • Los Angeles, California, United States, 90095
      • UCLA Hematology-Oncology Clinic
    • Los Angeles, California, United States, 90095
      • UCLA Hematology-Oncology Infusion Center
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
    • Vista, California, United States, 92081
      • UCSD Medical Center - Vista
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Aventura, Florida, United States, 33180
      • Mount Sinai Comprehensive Cancer Center - Aventura
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48109-5008
      • University of Michigan Hospitals
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201
      • Investigational Pharmacy, Karmanos Cancer Center
    • Farmington Hills, Michigan, United States, 48334
      • Karmanos Cancer Institute Weisberg Cancer Treatment Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10016
      • NYU Investigational Pharmacy
    • New York, New York, United States, 10065
      • Weill Cornell Medical College/New York Presbyterian Hospital
    • New York, New York, United States, 10010
      • VA NY Harbor Healthcare System
    • New York, New York, United States, 10016
      • NYU Laura and Isaac Perlmutter Cancer Center
    • New York, New York, United States, 10065
      • Research Pharmacy #PH#
  • North Carolina
    • Clinton, North Carolina, United States, 28328
      • Sampson Regional Medical Center
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center
    • Jacksonville, North Carolina, United States, 28546
      • Onslow Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPCI Investigational Drug Service
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic & Pharmacy
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Gynecologic Oncology Clinic
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Interventional Radiology
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford ENT Clinic
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford Research
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford USD Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, Pllc
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute / Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Oncology Pharmacy
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern Simmons Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

Number of Arms

19

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1; NSCLC patients treated with avelumab + utomilumab (Dose level 1)	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A2; NSCLC patients treated with avelumab + utomilumab (Dose level 2)	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A3; NSCLC patients treated with avelumab + utomilumab (Dose level 3)	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A4; Melanoma patients treated with avelumab +utomilumab	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A5; SCCHN patients treated with avelumab + utomilumab	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A6; TNBC patients treated with avelumab + utomilumab	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A7; SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A8; NSCLC first-line Stage IV treated with avelumab +PF-05082566	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Combination B Dose Escalation; PF-04518600 + avelumab in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: PF-04518600; OX40 Agonist
Experimental: Combination B Expansion Cohorts; PF-04518600 + avelumab in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: PF-04518600; OX40 Agonist
Experimental: Combination C Dose escalation cohorts; PD 0360324 + avelumab in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: PD 0360324; Anti-M-CSF
Experimental: Combination C Dose expansion cohorts; PD 0360324 + aveluamb in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: PD 0360324; Anti-M-CSF
Experimental: Combination D Dose escalation cohorts; PF-05082566 + PF-04518600 + avelumab in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566; Drug: PF-04518600; OX40 Agonist
Experimental: Combination D Dose expansion cohorts; PF-05082566 + PF-04518600 + avelumab in selected tumor types	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566; Drug: PF-04518600; OX40 Agonist
Experimental: Cohort A9; NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort A10; NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566
Experimental: Cohort F1; CMP-001 +avelumab in SCCHN	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: CMP-001; TLR9 agonist
Experimental: Cohort F2; CMP-001+avelumab+utomilumab in SCCHN	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: Utomilumab; Anti-4-1BB antibody; Other Names: PF-05082566; Drug: CMP-001; TLR9 agonist
Experimental: Cohort F3; CMP-001 +avelumab+PF-04518600 in SCCHN	Drug: Avelumab; Anti-PD-L1 antibody; Other Names: MSB0010718C; Drug: PF-04518600; OX40 Agonist; Drug: CMP-001; TLR9 agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b Lead-in: Number of Participants With First 2 Cycles Dose Limiting Toxicity (DLT) for Combination A	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.	Baseline up to Cycle 2 (up to 8 weeks)
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination B	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.	Baseline up to Cycle 2 (up to 8 weeks)
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination C	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.	Baseline up to Cycle 2 (up to 8 weeks)
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination D	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.	Baseline up to Cycle 2 (up to 8 weeks)
Phase 1b Lead-in: Number of Participants With First Cycle DLT for Combination F	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.	Baseline up to first Cycle (up to 4 weeks)
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	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.	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 53 months approximately)
Phase 2: Percentage of Participants With Confirmed OR as Per RECIST v 1.1 by Investigator Assessment for Combination B	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.	From start of the treatment until disease progression or death due to any cause, whichever occurred first (approximately 26 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination A	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.	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	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.	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 TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination C	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.	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)
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination D	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.	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	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.	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 Hematology Laboratory Test by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3: Combination A	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.	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 B	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.	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 C	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.	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 D	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.	Baseline up to end of treatment/withdrawal (maximum of 4.3 years)
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination F	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.	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	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.	Baseline up to end of treatment/withdrawal (maximum of 6.5 years)
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination B	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.	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	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.	Baseline up to end of treatment/withdrawal (maximum of 1.8 years)
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination D	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.	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	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.	Baseline up to end of treatment/withdrawal (maximum of 3 years)
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination A	Cmax is maximum observed plasma concentration.	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 Utomilumab in Combination A	Cmax is maximum observed plasma concentration.	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	Cmax is maximum observed plasma concentration.	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 and PD 0360324 in Combination C	Cmax is maximum observed plasma concentration.	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 Avelumab in Combination D	Cmax is maximum observed plasma concentration.	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
Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination D	Cmax is maximum observed plasma concentration.	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)
Maximum Observed Plasma Concentration (Cmax) of PF-04518600 in Combination D	Cmax is maximum observed plasma concentration.	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
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination F	Cmax is maximum observed plasma concentration.	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 A	Ctrough is steady-state pre-dose concentration.	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
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination A	Ctrough is steady-state pre-dose concentration.	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	Ctrough is steady-state pre-dose concentration.	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 Avelumab and PD 0360324 in Combination C	Ctrough is steady-state pre-dose concentration.	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 Avelumab in Combination D	Ctrough is steady-state pre-dose concentration.	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	Ctrough is steady-state pre-dose concentration.	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 PF-04518600 in Combination D	Ctrough is steady-state pre-dose concentration.	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 Avelumab in Combination F	Ctrough is steady-state pre-dose concentration.	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 Utomilumab in Combination F	Ctrough is steady-state pre-dose concentration.	Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2 and 4
Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination F	Ctrough is steady-state pre-dose concentration.	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 Anti-Drug Antibody (ADA) Against Avelumab For Combination A	ADA ever-positive was defined as at least one positive ADA result at any time point.	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 A	ADA ever-positive was defined as at least one positive ADA result at any time point.	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 B	ADA ever-positive was defined as at least one positive ADA result at any time point.	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Number of Participants With Positive ADA Levels For Combination C	ADA ever-positive was defined as at least one positive ADA result at any time point.	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	ADA ever-positive was defined as at least one positive ADA result at any time point.	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Number of Participants With Positive ADA Levels Against Utomilumab For Combination D	ADA ever-positive was defined as at least one positive ADA result at any time point.	Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12
Number of Participants With Positive ADA Levels Against Avelumab and PF-04518600 For Combination F	ADA ever-positive was defined as at least one positive ADA result at any time point.	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	ADA ever-positive was defined as at least one positive ADA result at any time point.	Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Time to Tumor Response (TTR) for Combination A	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.	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
TTR for Combination B	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.	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
TTR for Combination C	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.	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
TTR for Combination D	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.	From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
TTR for Combination F	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.	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	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.	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 B	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.	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 C	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.	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 D	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.	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	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.	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)
Progression-free Survival (PFS) for Combination A	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.	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 B	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.	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	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.	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 D	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.	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 F	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.	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	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.	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	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.	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 C	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.	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 D	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.	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 F	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.	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	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.	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	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.	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	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.	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 D	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.	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 F	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.	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	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%.	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 B	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%.	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	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%.	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 D	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%.	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	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%.	Baseline (Day 1)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2015
• Primary Completion (Actual): March 23, 2023
• Study Completion (Actual): March 23, 2023

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimated): September 18, 2015

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: bladder cancer; gastric cancer; melanoma; Non-small cell lung cancer (NSCLC); triple negative breast cancer (TNBC); Small cell lung cancer (SCLC); anti PD-L1; anti 4-1BB; OX40 agonist; anti M-CSF; TLR9 agonist; squamous cell carcinoma of head and neck (SCCHN); platinum resistant ovarian cancer; TGCT/PVNS
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: B9991004; 2015-002552-27 (EudraCT Number); JAVELIN MEDLEY (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.