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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
409
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.
Time frame: 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.
Time frame: 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.
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Anti-M-CSF
TLR9 agonist
UCSD Medical Center - Encinitas
Encinitas, California, United States
Koman Family Outpatient Pavilion
La Jolla, California, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
La Jolla, California, United States
UC San Diego Perlman Medical Offices
La Jolla, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
UCLA Clinical Research Unit (Adminstration Office)
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UCLA Hematology-Oncology Clinic
Los Angeles, California, United States
UCLA Hematology-Oncology Infusion Center
Los Angeles, California, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, United States
...and 78 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (approximately 26 months)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: Baseline (Day 1)