Clinical Trials /

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

NCT02554812

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: B9991004
  • SECONDARY ID: 2015-002552-27
  • SECONDARY ID: JAVELIN MEDLEY
  • NCT ID: NCT02554812

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
AvelumabMSB0010718CCohort A1
UtomilumabPF-05082566Cohort A1
PF-04518600Combination B Dose Escalation
PD 0360324Combination C Dose escalation cohorts
CMP-001Cohort F1

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.

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.
    

Trial Arms

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

Eligibility 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. 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose-Limiting Toxicities (DLT)
Time Frame:First 8 weeks of treatment (Combination A-D) First 4 weeks of treatment (CombinationF)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
Measure: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
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of PF-05082566
Measure: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
Safety Issue:
Description:Ctrough is defined as the trough plasma concentration at the end of an avelumab dosage interval.
Measure: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
Safety Issue:
Description:Ctrough is defined as the trough plasma concentration at the end of a PF-05082566 dosage interval.
Measure:Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C)
Time Frame:Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Safety Issue:
Description:Immunogenicity assessment of avelumab (MSB0010718C).
Measure:Anti-Drug Antibody (ADA) levels of PF-05082566
Time Frame:Pre-dose on Day 1 of Cycles 1, 3, 5, 8, and 12
Safety Issue:
Description:Immunogenicity assessment of PF-05082566.
Measure:Time to Tumor Response (TTR)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description: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.
Measure:Duration of Response (DR)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description: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.
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description: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.
Measure:Tumor tissue biomarkers
Time Frame:Baseline
Safety Issue:
Description:Tumor tissue biomarkers, including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes
Measure: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
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of PF-04518600
Measure:Anti-Drug Antibody (ADA) levels of PF-04518600
Time Frame:Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Safety Issue:
Description:Immunogenicity assessment of PF-04518600.
Measure: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
Safety Issue:
Description:Ctrough is defined as the trough plasma concentration at the end of a PF-04518600 dosage interval.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • anti PD-L1
  • anti 4-1BB
  • OX40 agonist
  • anti M-CSF
  • TLR9 agonist
  • Non-small cell lung cancer (NSCLC)
  • melanoma
  • squamous cell carcinoma of head and neck (SCCHN)
  • triple negative breast cancer (TNBC)
  • gastric cancer
  • Small cell lung cancer (SCLC)
  • bladder cancer
  • platinum resistant ovarian cancer
  • TGCT/PVNS

Last Updated