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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02554812




Registration number
NCT02554812
Ethics application status
Date submitted
16/09/2015
Date registered
18/09/2015

Titles & IDs
Public title
A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)
Scientific 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
Secondary ID [1] 0 0
2015-002552-27
Secondary ID [2] 0 0
B9991004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Drugs - Utomilumab
Treatment: Drugs - PF-04518600
Treatment: Drugs - PD 0360324
Treatment: Drugs - CMP-001

Experimental: Cohort A1 - NSCLC patients treated with avelumab + utomilumab (Dose level 1)

Experimental: Cohort A2 - NSCLC patients treated with avelumab + utomilumab (Dose level 2)

Experimental: Cohort A3 - NSCLC patients treated with avelumab + utomilumab (Dose level 3)

Experimental: Cohort A4 - Melanoma patients treated with avelumab +utomilumab

Experimental: Cohort A5 - SCCHN patients treated with avelumab + utomilumab

Experimental: Cohort A6 - TNBC patients treated with avelumab + utomilumab

Experimental: Cohort A7 - SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab

Experimental: Cohort A8 - NSCLC first-line Stage IV treated with avelumab +PF-05082566

Experimental: Combination B Dose Escalation - PF-04518600 + avelumab in selected tumor types

Experimental: Combination B Expansion Cohorts - PF-04518600 + avelumab in selected tumor types

Experimental: Combination C Dose escalation cohorts - PD 0360324 + avelumab in selected tumor types

Experimental: Combination C Dose expansion cohorts - PD 0360324 + aveluamb in selected tumor types

Experimental: Combination D Dose escalation cohorts - PF-05082566 + PF-04518600 + avelumab in selected tumor types

Experimental: Combination D Dose expansion cohorts - PF-05082566 + PF-04518600 + avelumab in selected tumor types

Experimental: Cohort A9 - NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)

Experimental: Cohort A10 - NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)

Experimental: Cohort F1 - CMP-001 +avelumab in SCCHN

Experimental: Cohort F2 - CMP-001+avelumab+utomilumab in SCCHN

Experimental: Cohort F3 - CMP-001 +avelumab+PF-04518600 in SCCHN


Treatment: Drugs: Avelumab
Anti-PD-L1 antibody

Treatment: Drugs: Utomilumab
Anti-4-1BB antibody

Treatment: Drugs: PF-04518600
OX40 Agonist

Treatment: Drugs: PD 0360324
Anti-M-CSF

Treatment: Drugs: CMP-001
TLR9 agonist
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b Lead-in: Number of Participants With First 2 Cycles Dose Limiting Toxicity (DLT) for Combination A
Timepoint [1] 0 0
Baseline up to Cycle 2 (up to 8 weeks)
Primary outcome [2] 0 0
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination B
Timepoint [2] 0 0
Baseline up to Cycle 2 (up to 8 weeks)
Primary outcome [3] 0 0
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination C
Timepoint [3] 0 0
Baseline up to Cycle 2 (up to 8 weeks)
Primary outcome [4] 0 0
Phase 1b Lead-in: Number of Participants With First 2 Cycles DLT for Combination D
Timepoint [4] 0 0
Baseline up to Cycle 2 (up to 8 weeks)
Primary outcome [5] 0 0
Phase 1b Lead-in: Number of Participants With First Cycle DLT for Combination F
Timepoint [5] 0 0
Baseline up to first Cycle (up to 4 weeks)
Primary outcome [6] 0 0
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
Timepoint [6] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 53 months approximately)
Primary outcome [7] 0 0
Phase 2: Percentage of Participants With Confirmed OR as Per RECIST v 1.1 by Investigator Assessment for Combination B
Timepoint [7] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (approximately 26 months)
Secondary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination A
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination B
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination C
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination D
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Number of Participants With TEAEs, Grade >= 3 TEAEs, Serious TEAEs and Treatment Related TEAEs: Combination F
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3: Combination A
Timepoint [6] 0 0
Baseline up to end of treatment/withdrawal (maximum of 6.5 years)
Secondary outcome [7] 0 0
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination B
Timepoint [7] 0 0
Baseline up to end of treatment/withdrawal (maximum of 3.5 years)
Secondary outcome [8] 0 0
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination C
Timepoint [8] 0 0
Baseline up to end of treatment/withdrawal (maximum of 1.8 years)
Secondary outcome [9] 0 0
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination D
Timepoint [9] 0 0
Baseline up to end of treatment/withdrawal (maximum of 4.3 years)
Secondary outcome [10] 0 0
Number of Participants With New Abnormal or Worsening Hematology Laboratory Test by Maximum CTCAE Grade >=3: Combination F
Timepoint [10] 0 0
Baseline up to end of treatment/withdrawal (maximum of 3 years)
Secondary outcome [11] 0 0
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination A
Timepoint [11] 0 0
Baseline up to end of treatment/withdrawal (maximum of 6.5 years)
Secondary outcome [12] 0 0
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination B
Timepoint [12] 0 0
Baseline up to end of treatment/withdrawal (maximum of 3.5 years)
Secondary outcome [13] 0 0
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination C
Timepoint [13] 0 0
Baseline up to end of treatment/withdrawal (maximum of 1.8 years)
Secondary outcome [14] 0 0
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination D
Timepoint [14] 0 0
Baseline up to end of treatment/withdrawal (maximum of 4.3 years)
Secondary outcome [15] 0 0
Number of Participants With New Abnormal or Worsening Chemistry Laboratory Test Results During the On-Treatment Period by Maximum CTCAE Grade >=3: Combination F
Timepoint [15] 0 0
Baseline up to end of treatment/withdrawal (maximum of 3 years)
Secondary outcome [16] 0 0
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination A
Timepoint [16] 0 0
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
Secondary outcome [17] 0 0
Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination A
Timepoint [17] 0 0
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
Secondary outcome [18] 0 0
Maximum Observed Plasma Concentration (Cmax) of Avelumab and PF-04518600 in Combination B
Timepoint [18] 0 0
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
Secondary outcome [19] 0 0
Maximum Observed Plasma Concentration (Cmax) of Avelumab and PD 0360324 in Combination C
Timepoint [19] 0 0
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
Secondary outcome [20] 0 0
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination D
Timepoint [20] 0 0
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
Secondary outcome [21] 0 0
Maximum Observed Plasma Concentration (Cmax) of Utomilumab in Combination D
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-04518600 in Combination D
Timepoint [22] 0 0
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
Secondary outcome [23] 0 0
Maximum Observed Plasma Concentration (Cmax) of Avelumab in Combination F
Timepoint [23] 0 0
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
Secondary outcome [24] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination A
Timepoint [24] 0 0
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
Secondary outcome [25] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination A
Timepoint [25] 0 0
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
Secondary outcome [26] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PF-04518600 in Combination B
Timepoint [26] 0 0
Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10
Secondary outcome [27] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab and PD 0360324 in Combination C
Timepoint [27] 0 0
Pre-dose on Days 1 and 15 of Cycle 1 (non-dosing); Day 1 of Cycles 2, 4, 6 and Cycle 10
Secondary outcome [28] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination D
Timepoint [28] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6 and Cycle 10; Day 15 of Cycle 1 (non-dosing)
Secondary outcome [29] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination D
Timepoint [29] 0 0
Pre-dose on Day 1 of Cycle 1, 3, 5, 8 and Cycle 12; Day 15 of Cycle 1 (non-dosing)
Secondary outcome [30] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination D
Timepoint [30] 0 0
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
Secondary outcome [31] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Avelumab in Combination F
Timepoint [31] 0 0
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
Secondary outcome [32] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of Utomilumab in Combination F
Timepoint [32] 0 0
Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycle 2 and 4
Secondary outcome [33] 0 0
Pre-Dose Observed Plasma Concentration (Ctrough) of PF-04518600 in Combination F
Timepoint [33] 0 0
Pre-dose on Day 1 of Cycle 1 (non-dosing); Pre-dose on Day 1 of Cycles 2 and 4
Secondary outcome [34] 0 0
Number of Participants With Positive Anti-Drug Antibody (ADA) Against Avelumab For Combination A
Timepoint [34] 0 0
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
Secondary outcome [35] 0 0
Number of Participants With Positive ADA Levels Against Utomilumab For Combination A
Timepoint [35] 0 0
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
Secondary outcome [36] 0 0
Number of Participants With Positive ADA Levels For Combination B
Timepoint [36] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Secondary outcome [37] 0 0
Number of Participants With Positive ADA Levels For Combination C
Timepoint [37] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Secondary outcome [38] 0 0
Number of Participants With Positive ADA Levels Against Avelumab and PF-04518600 For Combination D
Timepoint [38] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Secondary outcome [39] 0 0
Number of Participants With Positive ADA Levels Against Utomilumab For Combination D
Timepoint [39] 0 0
Pre-dose on Day 1 of Cycle 1, 3, 5, 8, 12
Secondary outcome [40] 0 0
Number of Participants With Positive ADA Levels Against Avelumab and PF-04518600 For Combination F
Timepoint [40] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Secondary outcome [41] 0 0
Number of Participants With Positive ADA Levels Against Utomilumab For Combination F
Timepoint [41] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 4, 6, and 10
Secondary outcome [42] 0 0
Time to Tumor Response (TTR) for Combination A
Timepoint [42] 0 0
From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
Secondary outcome [43] 0 0
TTR for Combination B
Timepoint [43] 0 0
From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
Secondary outcome [44] 0 0
TTR for Combination C
Timepoint [44] 0 0
From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
Secondary outcome [45] 0 0
TTR for Combination D
Timepoint [45] 0 0
From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
Secondary outcome [46] 0 0
TTR for Combination F
Timepoint [46] 0 0
From first dose of study drug until first documentation of CR or PR (maximum up to 7.3 years)
Secondary outcome [47] 0 0
Duration of Response (DR) for Combination A
Timepoint [47] 0 0
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)
Secondary outcome [48] 0 0
DR for Combination B
Timepoint [48] 0 0
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)
Secondary outcome [49] 0 0
DR for Combination C
Timepoint [49] 0 0
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)
Secondary outcome [50] 0 0
DR for Combination D
Timepoint [50] 0 0
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)
Secondary outcome [51] 0 0
DR for Combination F
Timepoint [51] 0 0
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)
Secondary outcome [52] 0 0
Progression-free Survival (PFS) for Combination A
Timepoint [52] 0 0
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)
Secondary outcome [53] 0 0
PFS for Combination B
Timepoint [53] 0 0
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)
Secondary outcome [54] 0 0
PFS for Combination C
Timepoint [54] 0 0
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)
Secondary outcome [55] 0 0
PFS for Combination D
Timepoint [55] 0 0
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)
Secondary outcome [56] 0 0
PFS for Combination F
Timepoint [56] 0 0
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)
Secondary outcome [57] 0 0
Overall Survival (OS) for Combination A
Timepoint [57] 0 0
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)
Secondary outcome [58] 0 0
OS for Combination B
Timepoint [58] 0 0
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)
Secondary outcome [59] 0 0
OS for Combination C
Timepoint [59] 0 0
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)
Secondary outcome [60] 0 0
OS for Combination D
Timepoint [60] 0 0
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)
Secondary outcome [61] 0 0
OS for Combination F
Timepoint [61] 0 0
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)
Secondary outcome [62] 0 0
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination A
Timepoint [62] 0 0
From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)
Secondary outcome [63] 0 0
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination B
Timepoint [63] 0 0
From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)
Secondary outcome [64] 0 0
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination C
Timepoint [64] 0 0
From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)
Secondary outcome [65] 0 0
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination D
Timepoint [65] 0 0
From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)
Secondary outcome [66] 0 0
Phase 1b: Percentage of Participants With Objective Response (OR) for Combination F
Timepoint [66] 0 0
From first dose of study drug until disease progression or death due to any cause (maximum up to 7.3 years)
Secondary outcome [67] 0 0
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
Timepoint [67] 0 0
Baseline (Day 1)
Secondary outcome [68] 0 0
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination B
Timepoint [68] 0 0
Baseline (Day 1)
Secondary outcome [69] 0 0
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination C
Timepoint [69] 0 0
Baseline (Day 1)
Secondary outcome [70] 0 0
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination D
Timepoint [70] 0 0
Baseline (Day 1)
Secondary outcome [71] 0 0
Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression and Tumor Infiltrating CD8+ Lymphocytes at Baseline for Combination F
Timepoint [71] 0 0
Baseline (Day 1)

Eligibility
Key inclusion criteria
* Histological or cytological diagnosis of advanced/metastatic solid tumor. Measurable disease by RECIST 1.1 with at least 1 measurable lesion that has not been previously irradiated. Availability of tumor specimen taken within 1 year prior to study entry, with no intervening systemic anti-cancer therapy. No prior PD-1/PDL-1 therapy allowed. Combination A: Phase 1b, patients with NSCLC that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, SCCHN, TNBC in any line of therapy, SCLC, 1st line NSCLC. 1st line NSCLC must demonstrate to express PD-L1. Activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination B: Phase 1b, patients with advanced solid tumors (NSCLC, SCCHN, melanoma) that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, or SCCHN. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. Activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination C: Ovarian cancer, SCCHN, NSCLC, gastric cancer, platinum resistant ovarian cancer. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. TGCT/PVNS that is either inoperable or requires extensive resection. Prior treatment with agents targeting CSF-1/CSF-1R not allowed. NSCLC activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Combination D: NSCLC, melanoma, SCCHN, bladder cancer. NSCLC activating EGFR mutation, ALK, ROS1 translocation/rearrangements are not permitted. Up to 2 lines of prior therapy in advanced/metastatic disease setting allowed. Combination F: Recurrent or metastatic SCCHN. One to three prior lines of systemic therapy for advanced stage or metastatic disease. Patients must have received anti PD-1/PD-L1 containing therapy (requires at least two doses of PD-1/PD-L1 agent).Disease progression no earlier than 6 weeks from initiation of the latest anticancer therapy. Evidence of radiologic progression is required. • Patient must be a candidate for intralesional administration with at least one tumor lesion which can be injected safely.
* ECOG performance status 0 or 1
* Estimated life expectancy of at least 3 months
* Adequate bone marrow, renal, and liver function
* Resolved acute effects of prior therapy
* Negative serum pregnancy test at screening
* Male and female patients able to have children must agree to use at least 1 highly effective method of contraception throughout the study and for at least 90 days after last dose
* Signed and dated informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry. Combination F:PD-1/PD-L1 agent within 14 days prior study entry.
* Current or prior use of immunosuppressive medication within 7 days prior to study entry
* Active autoimmune disease requiring systemic steroids or immunosuppressive agents within 7 days prior to study entry
* Known prior or suspected hypersensitivity to investigational products
* Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry
* Patients with known symptomatic brain metastases requiring steroids
* Previous high-dose chemotherapy requiring stem cell rescue
* Prior allogeneic stem cell transplant or organ graft
* Any of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* Symptomatic pulmonary embolism within 6 months prior to study entry
* Known HIV or AIDS-related illness
* Active infection requiring systemic therapy
* Positive HBV or HCV test indicating acute or chronic infection
* Administration of a live vaccine within 4 weeks prior to study entry
* Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason =6) prostate cancer
* Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
* Persisting toxicity related to prior therapy >Grade 1
* Other severe acute or chronic medical condition
* Combo C :Existing periorbital edema.
* Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture (within 12 weeks prior study entry)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/03/2023
Sample size
Target
Accrual to date
Final
409
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Macquarie University - Macquarie University
Recruitment hospital [3] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [4] 0 0
The Mater Hospital - North Sydney
Recruitment hospital [5] 0 0
Baxter Healthcare - Old Toongabie
Recruitment hospital [6] 0 0
Brighton Medical Imaging - Brighton
Recruitment hospital [7] 0 0
Cabrini Hospital Brighton - Brighton
Recruitment hospital [8] 0 0
Austin Health - Heidelberg
Recruitment hospital [9] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [10] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [11] 0 0
Malvern Medical Imaging - Malvern
Recruitment hospital [12] 0 0
Macquarie Heart - New South Wales
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - Macquarie University
Recruitment postcode(s) [3] 0 0
2060 - North Sydney
Recruitment postcode(s) [4] 0 0
2146 - Old Toongabie
Recruitment postcode(s) [5] 0 0
3186 - Brighton
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3144 - Malvern
Recruitment postcode(s) [8] 0 0
2109 - New South Wales
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Rhode Island
Country [10] 0 0
United States of America
State/province [10] 0 0
South Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Cedex
Country [19] 0 0
France
State/province [19] 0 0
Villejuif
Country [20] 0 0
Japan
State/province [20] 0 0
Chiba
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Poland
State/province [22] 0 0
Mazowieckie
Country [23] 0 0
Poland
State/province [23] 0 0
Warszawa
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taipei
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02554812