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

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ClinicalTrials.gov Identifier: NCT02554812
Recruitment Status : Recruiting
First Posted : September 18, 2015
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 16, 2015
First Posted Date  ICMJE September 18, 2015
Last Update Posted Date October 14, 2019
Actual Study Start Date  ICMJE November 9, 2015
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Number of participants with Dose-Limiting Toxicities (DLT) [ Time Frame: First 8 weeks of treatment (Combination A-D) First 4 weeks of treatment (CombinationF) ]
    For Phase 1b: DLTs for Combination A (avelumab and PF-05082566) or Combination B (avelumab and PF-04518600) or Combination C (avelumab and PD 0360324) or Combination D (Avelumab and utomilumab and PF-04518600)occurring during the first 8 weeks of treatment (first 2 cycles). For Phase 1b: DLT for Combination F (avelumab plus CMP-001 and utomilumab or PF-04518600) occurring during the first 4 weeks of treatment (first cycle).
  • Objective Response - Number of Participants With Objective Response [ Time Frame: Baseline up to approximately 24 months ]
    For Phase 2: Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1).
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
  • Number of participants with Dose-Limiting Toxicities (DLT) [ Time Frame: First 8 weeks of treatment ]
    For Phase 1b: DLTs for the combination of avelumab and PF-05082566 occurring during the first 8 weeks of treatment (first 2 cycles).
  • Objective Response - Number of Participants With Objective Response [ Time Frame: Baseline up to approximately 24 months ]
    For Phase 2: Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1).
Change History Complete list of historical versions of study NCT02554812 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2016)
  • Cmax of avelumab (MSB0010718C) [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
  • Cmax of PF-05082566 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12 ]
    Cmax defined as the maximum plasma concentration of PF-05082566
  • Ctrough of avelumab (MSB0010718C) [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Ctrough is defined as the trough plasma concentration at the end of an avelumab dosage interval.
  • Ctrough of PF-05082566 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12 ]
    Ctrough is defined as the trough plasma concentration at the end of a PF-05082566 dosage interval.
  • Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C) [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10 ]
    Immunogenicity assessment of avelumab (MSB0010718C).
  • Anti-Drug Antibody (ADA) levels of PF-05082566 [ Time Frame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, and 12 ]
    Immunogenicity assessment of PF-05082566.
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
    Time to Tumor Response (TTR) is defined for patients with confirmed objective response (CR or PR) as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the first documentation of objective tumor response.
  • Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 months ]
    Duration of Response (DR) is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
    Progression-Free Survival (PFS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 24 months ]
    Overall Survival (OS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of death.
  • Tumor tissue biomarkers [ Time Frame: Baseline ]
    Tumor tissue biomarkers, including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes
  • Cmax of PF-04518600 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Cmax defined as the maximum plasma concentration of PF-04518600
  • Anti-Drug Antibody (ADA) levels of PF-04518600 [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10 ]
    Immunogenicity assessment of PF-04518600.
  • Ctrough of PF-04518600 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Ctrough is defined as the trough plasma concentration at the end of a PF-04518600 dosage interval.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
  • Cmax of avelumab (MSB0010718C) [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
  • Cmax of PF-05082566 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12 ]
    Cmax defined as the maximum plasma concentration of PF-05082566
  • Ctrough of avelumab (MSB0010718C) [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10 ]
    Ctrough is defined as the trough plasma concentration at the end of an avelumab dosage interval.
  • Ctrough of PF-05082566 [ Time Frame: Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12 ]
    Ctrough is defined as the trough plasma concentration at the end of a PF-05082566 dosage interval.
  • Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C) [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10 ]
    Immunogenicity assessment of avelumab (MSB0010718C).
  • Anti-Drug Antibody (ADA) levels of PF-05082566 [ Time Frame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, and 12 ]
    Immunogenicity assessment of PF-05082566.
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
    Time to Tumor Response (TTR) is defined for patients with confirmed objective response (CR or PR) as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the first documentation of objective tumor response.
  • Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 months ]
    Duration of Response (DR) is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
    Progression-Free Survival (PFS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 24 months ]
    Overall Survival (OS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of death.
  • Tumor tissue biomarkers [ Time Frame: Baseline ]
    Tumor tissue biomarkers, including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)
Official Title  ICMJE 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
Brief 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. 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.
Detailed Description

This is a Phase 1b/2, open-label, multi-center, multiple-dose, safety, clinical activity, PK, and PD study of avelumab in combination with other immune modulators in adult patients with locally advanced or metastatic solid tumors (eg, non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), gastric cancer, platinum resistant ovarian cancer, bladder cancer, small cell lung cancer (SCLC) and progressing tenosynovial giant cell tumor/pigmented villonodular synovitis (TGCT/PVNS) . In Phase 1b, this includes patients whose disease has progressed on standard of care therapy or for whom no standard therapy is available. In Phase 2, enrollment criteria regarding prior treatment(s) received varies by tumor type. Incorporation of the other immune modulators into this study is based on preclinical and clinical data supportive of single-agent tolerability and potential clinical benefit, as well as non-clinical data suggesting safety, tolerability and clinical benefit of the agent(s) in combination with avelumab. Combinations of avelumab plus other immune modulator(s) to be evaluated are as follows:

  • Combination A: avelumab plus utomilumab (4-1BB agonist mAb)
  • Combination B: avelumab plus PF-04518600 (OX40 agonist mAb)
  • Combination C: avelumab plus PD 0360324 (M-CSF mAb)
  • Combination D: avelumab plus utomilumab plus PF-04518600
  • Combination F: avelumab plus CMP-001 (TLR9 agonist) and avelumab plus CMP-001 plus utomilumab and avelumab plus CMP-001 and PF-04518600 Each combination will be studied individually in 2 study parts: 1) a Phase 1b Lead-in part to evaluate safety, and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and RP2D (if applicable), of the combination, and 2) a Phase 2 part to evaluate efficacy and further evaluate safety of the selected dose from the Phase 1b portion in pre-specified patient populations.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Cancer
Intervention  ICMJE
  • Drug: Avelumab
    Anti-PD-L1 antibody
    Other Name: MSB0010718C
  • Drug: Utomilumab
    Anti-4-1BB antibody
    Other Name: PF-05082566
  • Drug: PF-04518600
    OX40 Agonist
  • Drug: PD 0360324
    Anti-M-CSF
  • Drug: CMP-001
    TLR9 agonist
Study Arms  ICMJE
  • Experimental: Cohort A1
    NSCLC patients treated with avelumab + utomilumab (Dose level 1)
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A2
    NSCLC patients treated with avelumab + utomilumab (Dose level 2)
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A3
    NSCLC patients treated with avelumab + utomilumab (Dose level 3)
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A4
    Melanoma patients treated with avelumab +utomilumab
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A5
    SCCHN patients treated with avelumab + utomilumab
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A6
    TNBC patients treated with avelumab + utomilumab
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A7
    SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A8
    NSCLC first-line Stage IV treated with avelumab +PF-05082566
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Combination B Dose Escalation
    PF-04518600 + avelumab in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: PF-04518600
  • Experimental: Combination B Expansion Cohorts
    PF-04518600 + avelumab in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: PF-04518600
  • Experimental: Combination C Dose escalation cohorts
    PD 0360324 + avelumab in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: PD 0360324
  • Experimental: Combination C Dose expansion cohorts
    PD 0360324 + aveluamb in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: PD 0360324
  • Experimental: Combination D Dose escalation cohorts
    PF-05082566 + PF-04518600 + avelumab in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
    • Drug: PF-04518600
  • Experimental: Combination D Dose expansion cohorts
    PF-05082566 + PF-04518600 + avelumab in selected tumor types
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
    • Drug: PF-04518600
  • Experimental: Cohort A9
    NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort A10
    NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
  • Experimental: Cohort F1
    CMP-001 +avelumab in SCCHN
    Interventions:
    • Drug: Avelumab
    • Drug: CMP-001
  • Experimental: Cohort F2
    CMP-001+avelumab+utomilumab in SCCHN
    Interventions:
    • Drug: Avelumab
    • Drug: Utomilumab
    • Drug: CMP-001
  • Experimental: Cohort F3
    CMP-001 +avelumab+PF-04518600 in SCCHN
    Interventions:
    • Drug: Avelumab
    • Drug: PF-04518600
    • Drug: CMP-001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 10, 2019)
620
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2015)
147
Estimated Study Completion Date  ICMJE December 16, 2022
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 as the last systemic cancer treatment, with disease progression no earlier than 6 weeks from initiation of therapy. The last dose of prior PD-1/PD-L1 agent must be no more than 24 weeks from patient enrollment with no intervening therapy. Evidence of radiologic progression is required. Patient must have at least one injectable tumor lesion
  • ECOG performance status 0 or 1
  • Estimated life expectancy of at least 3 months
  • Adequate bone marrow, renal, and liver function
  • Resolved acute effects of prior therapy
  • Negative serum pregnancy test at screening
  • Male and female patients able to have children must agree to use at least 1 highly effective method of contraception throughout the study and for at least 90 days after last dose
  • Signed and dated informed consent

Exclusion Criteria:

  • Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry. Combination F:PD-1/PD-L1 agent within 14 days prior study entry.
  • Current or prior use of immunosuppressive medication within 7 days prior to study entry
  • Active autoimmune disease requiring systemic steroids or immunosuppressive agents within 7 days prior to study entry
  • Known prior or suspected hypersensitivity to investigational products
  • Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry
  • Patients with known symptomatic brain metastases requiring steroids
  • Previous high-dose chemotherapy requiring stem cell rescue
  • Prior allogeneic stem cell transplant or organ graft
  • Any of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • Symptomatic pulmonary embolism within 6 months prior to study entry
  • Known HIV or AIDS-related illness
  • Active infection requiring systemic therapy
  • Positive HBV or HCV test indicating acute or chronic infection
  • Administration of a live vaccine within 4 weeks prior to study entry
  • Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason ≤6) prostate cancer
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
  • Persisting toxicity related to prior therapy >Grade 1
  • Other severe acute or chronic medical condition
  • Combo C :Existing periorbital edema.
  • Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture (within 12 weeks prior study entry)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Japan,   Poland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02554812
Other Study ID Numbers  ICMJE B9991004
2015-002552-27 ( EudraCT Number )
JAVELIN MEDLEY ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP