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Advanced CancerPhase 1/2NCT02554812

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

A Phase 1/2 study testing Avelumab, Utomilumab and PF-04518600 in people with Advanced Cancer, run by Pfizer at 88 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1b/2 dose-optimization study to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of avelumab (MSB0010718C) in combination with other cancer immunotherapies in patients with locally advanced or metastatic solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Cancer
What is being tested?
Avelumab, Utomilumab and PF-04518600
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
409 participants
Where
88 sitesin 8 countries
Study dates
9 Nov 2015to 23 Mar 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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)

Trial locations and contacts

88 sites in 8 countries.

88 sites in 8 countries

United States57 sites

  • University of Michigan Hospitals

    Ann Arbor, Michigan, 48109-5008

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Mount Sinai Comprehensive Cancer Center - Aventura

    Aventura, Florida, 33180

  • Sampson Regional Medical Center

    Clinton, North Carolina, 28328

  • Southeastern Medical Oncology Center

    Clinton, North Carolina, 28328

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • UT Southwestern Simmons Comprehensive Cancer Center

    Dallas, Texas, 75390

  • Investigational Pharmacy, Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • UCSD Medical Center - Encinitas

    Encinitas, California, 92024

  • Karmanos Cancer Institute Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Southeastern Medical Oncology Center

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Onslow Memorial Hospital

    Jacksonville, North Carolina, 28546

  • Southeastern Medical Oncology Center

    Jacksonville, North Carolina, 28546

  • Koman Family Outpatient Pavilion

    La Jolla, California, 92037

  • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)

    La Jolla, California, 92037

  • UC San Diego Perlman Medical Offices

    La Jolla, California, 92037

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • UCLA Clinical Research Unit (Adminstration Office)

    Los Angeles, California, 90024

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

  • UCLA Hematology-Oncology Clinic

    Los Angeles, California, 90095

  • UCLA Hematology-Oncology Infusion Center

    Los Angeles, California, 90095

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • The Sarah Cannon Research Institute / Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • Henry-Joyce Cancer Clinic

    Nashville, Tennessee, 37232

  • Vanderbilt University Oncology Pharmacy

    Nashville, Tennessee, 37232

  • VA NY Harbor Healthcare System

    New York, New York, 10010

  • NYU Investigational Pharmacy

    New York, New York, 10016

  • NYU Langone Medical Center

    New York, New York, 10016

  • NYU Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Weill Cornell Medical College

    New York, New York, 10021

  • Research Pharmacy #PH#

    New York, New York, 10065

  • Weill Cornell Medical College/New York Presbyterian Hospital

    New York, New York, 10065

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • UPCI Investigational Drug Service

    Pittsburgh, Pennsylvania, 15232

  • UPMC Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Miriam Hospital

    Providence, Rhode Island, 02906

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Sanford Cancer Center Oncology Clinic & Pharmacy

    Sioux Falls, South Dakota, 57104

  • Sanford Gynecologic Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Sanford Interventional Radiology

    Sioux Falls, South Dakota, 57104

  • Sanford ENT Clinic

    Sioux Falls, South Dakota, 57105

  • Sanford Research

    Sioux Falls, South Dakota, 57105

  • Sanford USD Medical Center

    Sioux Falls, South Dakota, 57105

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • UCSD Medical Center - Vista

    Vista, California, 92081

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Australia12 sites

  • Brighton Medical Imaging

    Brighton, Victoria, 3186

  • Cabrini Hospital Brighton

    Brighton, Victoria, 3186

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Austin Health

    Heidelberg, Victoria, 3084

  • Macquarie University

    Macquarie University, New South Wales, 2109

  • Cabrini Hospital Malvern

    Malvern, Victoria, 3144

  • Cabrini Hospital

    Malvern, Victoria, 3144

  • Malvern Medical Imaging

    Malvern, Victoria, 3144

  • Macquarie Heart

    New South Wales, 2109

  • Melanoma Institute Australia

    North Sydney, New South Wales, 2060

  • The Mater Hospital

    North Sydney, New South Wales, 2060

  • Baxter Healthcare

    Old Toongabie, New South Wales, 2146

Other trials in Australia

Canada6 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • PH 145294, Centre Hospitalier de l'Universite de Montreal (CHUM), Oncology Research Pharmacy

    Montreal, Quebec, H2X 0C2

  • Centre Hospitalier de l'Université de Montréal (CHUM)

    Montreal, Quebec, H2X 3E4

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

  • British Columbia Cancer Agency - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

United Kingdom5 sites

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Sarah Cannon Research Institute UK

    London, W1G 6AD

  • The Harley Street Clinic

    London, W1G 7LJ

  • The Harley Street Clinic

    London, W1G 8PP

Other trials in United Kingdom

France2 sites

  • Institut Gustave Roussy

    Villejuif, Cedex, 94805

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Japan2 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

Other trials in Japan

Poland2 sites

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

    Warsaw, Masovian Voivodeship, 02-781

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

    Warsaw, 02-781

Other trials in Poland

Taiwan2 sites

  • Investigational Drug Services, National Taiwan University Hospital

    Taipei, 100

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

About this study

Official title: 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.

Read the 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.
Conditions
Advanced Cancer
Being tested
Avelumab, Utomilumab, PF-04518600, PD 0360324, CMP-001
Keywords
anti PD-L1, anti 4-1BB, OX40 agonist, anti M-CSF, TLR9 agonist, Non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of head and neck (SCCHN), triple negative breast cancer (TNBC), gastric cancer, Small cell lung cancer (SCLC), bladder cancer, platinum resistant ovarian cancer, TGCT/PVNS
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Melanoma, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Neoplasms, Stomach Neoplasms, Small Cell Lung Carcinoma, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called MSB0010718C

    Anti-PD-L1 antibody

  • UtomilumabDrug

    Also called PF-05082566

    Anti-4-1BB antibody

  • PF-04518600Drug

    OX40 Agonist

  • PD 0360324Drug

    Anti-M-CSF

  • CMP-001Drug

    TLR9 agonist

Study groups in NCT02554812
Study groupRoleWhat they receive
Cohort A1ExperimentalNSCLC patients treated with avelumab + utomilumab (Dose level 1)
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A2ExperimentalNSCLC patients treated with avelumab + utomilumab (Dose level 2)
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A3ExperimentalNSCLC patients treated with avelumab + utomilumab (Dose level 3)
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A4ExperimentalMelanoma patients treated with avelumab +utomilumab
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A5ExperimentalSCCHN patients treated with avelumab + utomilumab
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A6ExperimentalTNBC patients treated with avelumab + utomilumab
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A7ExperimentalSCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A8ExperimentalNSCLC first-line Stage IV treated with avelumab +PF-05082566
Receives: Drug: Avelumab; Drug: Utomilumab
Combination B Dose EscalationExperimentalPF-04518600 + avelumab in selected tumor types
Receives: Drug: Avelumab; Drug: PF-04518600
Combination B Expansion CohortsExperimentalPF-04518600 + avelumab in selected tumor types
Receives: Drug: Avelumab; Drug: PF-04518600
Combination C Dose escalation cohortsExperimentalPD 0360324 + avelumab in selected tumor types
Receives: Drug: Avelumab; Drug: PD 0360324
Combination C Dose expansion cohortsExperimentalPD 0360324 + aveluamb in selected tumor types
Receives: Drug: Avelumab; Drug: PD 0360324
Combination D Dose escalation cohortsExperimentalPF-05082566 + PF-04518600 + avelumab in selected tumor types
Receives: Drug: Avelumab; Drug: Utomilumab; Drug: PF-04518600
Combination D Dose expansion cohortsExperimentalPF-05082566 + PF-04518600 + avelumab in selected tumor types
Receives: Drug: Avelumab; Drug: Utomilumab; Drug: PF-04518600
Cohort A9ExperimentalNSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort A10ExperimentalNSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
Receives: Drug: Avelumab; Drug: Utomilumab
Cohort F1ExperimentalCMP-001 +avelumab in SCCHN
Receives: Drug: Avelumab; Drug: CMP-001
Cohort F2ExperimentalCMP-001+avelumab+utomilumab in SCCHN
Receives: Drug: Avelumab; Drug: Utomilumab; Drug: CMP-001
Cohort F3ExperimentalCMP-001 +avelumab+PF-04518600 in SCCHN
Receives: Drug: Avelumab; Drug: PF-04518600; Drug: CMP-001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to Cycle 2 (up to 8 weeks)

  2. 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.

    Measured: Baseline up to Cycle 2 (up to 8 weeks)

  3. 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.

    Measured: Baseline up to Cycle 2 (up to 8 weeks)

  4. 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.

    Measured: Baseline up to Cycle 2 (up to 8 weeks)

  5. 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.

    Measured: Baseline up to first Cycle (up to 4 weeks)

  6. 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.

    Measured: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 53 months approximately)

  7. 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.

    Measured: From start of the treatment until disease progression or death due to any cause, whichever occurred first (approximately 26 months)

Secondary outcomes (71)

  1. 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.

    Measured: 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)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: 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)

  4. 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.

    Measured: 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)

  5. 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.

    Measured: 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)

  6. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 6.5 years)

  7. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 3.5 years)

  8. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 1.8 years)

  9. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 4.3 years)

  10. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 3 years)

  11. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 6.5 years)

  12. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 3.5 years)

  13. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 1.8 years)

  14. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 4.3 years)

  15. 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.

    Measured: Baseline up to end of treatment/withdrawal (maximum of 3 years)

  16. Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination A

    Cmax is maximum observed plasma concentration.

    Measured: 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

  17. Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination A

    Cmax is maximum observed plasma concentration.

    Measured: 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

  18. Maximum Observed Plasma Concentration (Cmax) of Avelumab and PF-04518600 in Combination B

    Cmax is maximum observed plasma concentration.

    Measured: 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

  19. Maximum Observed Plasma Concentration (Cmax) of Avelumab and PD 0360324 in Combination C

    Cmax is maximum observed plasma concentration.

    Measured: 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

  20. Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination D

    Cmax is maximum observed plasma concentration.

    Measured: 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

  21. Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination D

    Cmax is maximum observed plasma concentration.

    Measured: 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)

  22. Maximum Observed Plasma Concentration (Cmax) of PF-04518600 in Combination D

    Cmax is maximum observed plasma concentration.

    Measured: 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

  23. Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination F

    Cmax is maximum observed plasma concentration.

    Measured: 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

  24. Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination A

    Ctrough is steady-state pre-dose concentration.

    Measured: 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

  25. Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination A

    Ctrough is steady-state pre-dose concentration.

    Measured: 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

  26. Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PF-04518600 in Combination B

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10

  27. Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PD 0360324 in Combination C

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10

  28. Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination D

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6 and Cycle 10; Day 15 of Cycle 1 (non-dosing)

  29. Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination D

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Day 1 of Cycle 1, 3, 5, 8 and Cycle 12; Day 15 of Cycle 1 (non-dosing)

  30. Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination D

    Ctrough is steady-state pre-dose concentration.

    Measured: 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

  31. Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination F

    Ctrough is steady-state pre-dose concentration.

    Measured: 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

  32. Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination F

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2 and 4

  33. Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination F

    Ctrough is steady-state pre-dose concentration.

    Measured: Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycles 2 and 4

  34. 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.

    Measured: 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

  35. 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.

    Measured: 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

  36. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10

  37. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10

  38. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10

  39. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12

  40. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10

  41. 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.

    Measured: Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10

  42. 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.

    Measured: From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)

  43. 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.

    Measured: From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)

  44. 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.

    Measured: From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)

  45. 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.

    Measured: From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)

  46. 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.

    Measured: From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)

  47. 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.

    Measured: 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)

  48. 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.

    Measured: 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)

  49. 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.

    Measured: 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)

  50. 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.

    Measured: 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)

  51. 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.

    Measured: 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)

  52. 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.

    Measured: 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)

  53. 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.

    Measured: 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)

  54. 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.

    Measured: 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)

  55. 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.

    Measured: 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)

  56. 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.

    Measured: 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)

  57. 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.

    Measured: 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)

  58. 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.

    Measured: 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)

  59. 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.

    Measured: 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)

  60. 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.

    Measured: 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)

  61. 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.

    Measured: 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)

  62. 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.

    Measured: From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)

  63. 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.

    Measured: From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)

  64. 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.

    Measured: From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)

  65. 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.

    Measured: From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)

  66. 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.

    Measured: From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)

  67. 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%.

    Measured: Baseline (Day 1)

  68. 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%.

    Measured: Baseline (Day 1)

  69. 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%.

    Measured: Baseline (Day 1)

  70. 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%.

    Measured: Baseline (Day 1)

  71. 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%.

    Measured: Baseline (Day 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2015 (estimated)
  2. Study start9 Nov 2015
  3. Primary completion23 Mar 2023
  4. Study completion23 Mar 2023

Why it stopped: The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
409 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02554812
Sponsor's protocol ID
B9991004
Other IDs
2015-002552-27, JAVELIN MEDLEY, 2015
Status last verified
Jul 2024
First submitted
16 Sep 2015
Last updated
30 Jul 2024
Data monitoring committee
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Avelumab, Utomilumab and PF-04518600 in people with Advanced Cancer, run by Pfizer at 88 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 88 sites in United States, Australia, Canada, United Kingdom, France and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b Lead-in: Number of Participants With First 2 Cycles Dose Limiting Toxicity (DLT) for Combination A (time frame: Baseline up to Cycle 2 (up to 8 weeks)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02554812.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2024.

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