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Trial record 1 of 1 for:    B9991004
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A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)

This study is currently recruiting participants.
Verified December 2017 by Pfizer
Sponsor:
ClinicalTrials.gov Identifier:
NCT02554812
First Posted: September 18, 2015
Last Update Posted: December 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  Purpose
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.

Condition Intervention Phase
Advanced Cancer Drug: Avelumab Drug: Utomilumab Drug: PF-04518600 Drug: PD 0360324 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Open-label Study To Evaluate Safety, Clinical Activity, Pharmacokinetics And Pharmacodynamics Of Avelumab (msb0010718c) In Combination With Other Cancer Immunotherapies In Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with Dose-Limiting Toxicities (DLT) [ Time Frame: First 8 weeks of treatment ]
    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).

  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 560
Actual Study Start Date: November 9, 2015
Estimated Study Completion Date: February 21, 2020
Estimated Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A1
NSCLC patients treated with avelumab + utomilumab (Dose level 1)
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A2
NSCLC patients treated with avelumab + utomilumab (Dose level 2)
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A3
NSCLC patients treated with avelumab + utomilumab (Dose level 3)
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A4
Melanoma patients treated with avelumab +utomilumab
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A5
SCCHN patients treated with avelumab + utomilumab
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A6
TNBC patients treated with avelumab + utomilumab
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A7
SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A8
NSCLC first-line Stage IV treated with avelumab +PF-05082566
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Combination B Dose Escalation
PF-04518600 + avelumab in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: PF-04518600
PF-04518600 will be administered at increasing dose levels in combination with avelumab.
Experimental: Combination B Expansion Cohorts
PF-04518600 + avelumab in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: PF-04518600
PF-04518600 will be administered at increasing dose levels in combination with avelumab.
Experimental: Combination C Dose escalation cohorts
PD 0360324 + avelumab in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: PD 0360324
PD 0360324 will be administered at increasing dose levels in combination with avelumab.
Experimental: Combination C Dose expansion cohorts
PD 0360324 + aveluamb in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: PD 0360324
PD 0360324 will be administered at increasing dose levels in combination with avelumab.
Experimental: Combination D Dose escalation cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Drug: PF-04518600
PF-04518600 will be administered at increasing dose levels in combination with avelumab.
Experimental: Combination D Dose expansion cohorts
PF-05082566 + PF-04518600 + avelumab in selected tumor types
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Drug: PF-04518600
PF-04518600 will be administered at increasing dose levels in combination with avelumab.
Experimental: Cohort A9
NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566
Experimental: Cohort A10
NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)
Drug: Avelumab
Anti-PD-L1 antibody given until disease progression.
Other Name: MSB0010718C
Drug: Utomilumab
Anti-4-1BB antibody at 1 of 3 dose levels to optimize the combination with avelumab. Treatment with the combination of avelumab and PF-05082566 will continue until disease progression.
Other Name: PF-05082566

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 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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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 2 highly effective methods of contraception throughout the study and for at least 60 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.
  • 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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02554812


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 69 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02554812     History of Changes
Other Study ID Numbers: B9991004
2015-002552-27 ( EudraCT Number )
JAVELIN MEDLEY ( Other Identifier: Alias Study Number )
First Submitted: September 16, 2015
First Posted: September 18, 2015
Last Update Posted: December 14, 2017
Last Verified: December 2017

Keywords provided by Pfizer:
anti PD-L1
anti 4-1BB
OX40 agonist
anti M-CSF
Non-small cell lung cancer (NSCLC)
melanoma
squamous cell carcinoma of head and neck (SCCHN)
triple negative breast cancer (TNBC)
gastric cancer
Small cell lung cancer (SCLC)
bladder cancer
platinum resistant ovarian cancer
TGCT/PVNS

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs