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

Advanced Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02554812
• Other study ID #: B9991004
• Secondary ID: 2015-002552-27JA
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 9, 2015
• Est. completion date: March 23, 2023

Study information

• Verified date: June 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 409
• Est. completion date: March 23, 2023
• Est. primary completion date: March 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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)

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

Drug:
• Avelumab
Anti-PD-L1 antibody
• Utomilumab
Anti-4-1BB antibody
• PF-04518600
OX40 Agonist
• PD 0360324
Anti-M-CSF
• CMP-001
TLR9 agonist

Locations

Country	Name	City	State
Australia	Brighton Medical Imaging	Brighton	Victoria
Australia	Cabrini Hospital Brighton	Brighton	Victoria
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Macquarie University	Macquarie University	New South Wales
Australia	Cabrini Hospital	Malvern	Victoria
Australia	Cabrini Hospital Malvern	Malvern	Victoria
Australia	Malvern Medical Imaging	Malvern	Victoria
Australia	Macquarie Heart	New South Wales
Australia	Melanoma Institute Australia	North Sydney	New South Wales
Australia	The Mater Hospital	North Sydney	New South Wales
Australia	Baxter Healthcare	Old Toongabie	New South Wales
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Centre Hospitalier de l'Université de Montréal (CHUM)	Montreal	Quebec
Canada	PH 145294, Centre Hospitalier de l'Universite de Montreal (CHUM), Oncology Research Pharmacy	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia
France	Institut Gustave Roussy	Villejuif	Cedex
France	Institut Gustave Roussy	Villejuif
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa
Taiwan	Investigational Drug Services, National Taiwan University Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	The Harley Street Clinic	London
United Kingdom	The Harley Street Clinic	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Michigan Hospitals	Ann Arbor	Michigan
United States	Mount Sinai Comprehensive Cancer Center - Aventura	Aventura	Florida
United States	Sampson Regional Medical Center	Clinton	North Carolina
United States	Southeastern Medical Oncology Center	Clinton	North Carolina
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Simmons Comprehensive Cancer Center	Dallas	Texas
United States	Investigational Pharmacy, Karmanos Cancer Center	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	UCSD Medical Center - Encinitas	Encinitas	California
United States	Karmanos Cancer Institute Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center	Jacksonville	North Carolina
United States	Koman Family Outpatient Pavilion	La Jolla	California
United States	UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UC San Diego Perlman Medical Offices	La Jolla	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	UCLA Clinical Research Unit (Adminstration Office)	Los Angeles	California
United States	UCLA Hematology-Oncology Clinic	Los Angeles	California
United States	UCLA Hematology-Oncology Infusion Center	Los Angeles	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	The Sarah Cannon Research Institute / Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Vanderbilt University Oncology Pharmacy	Nashville	Tennessee
United States	NYU Investigational Pharmacy	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	NYU Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	Research Pharmacy #PH#	New York	New York
United States	VA NY Harbor Healthcare System	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Weill Cornell Medical College/New York Presbyterian Hospital	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	UPCI Investigational Drug Service	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Sanford Cancer Center Oncology Clinic & Pharmacy	Sioux Falls	South Dakota
United States	Sanford ENT Clinic	Sioux Falls	South Dakota
United States	Sanford Gynecologic Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford Interventional Radiology	Sioux Falls	South Dakota
United States	Sanford Research	Sioux Falls	South Dakota
United States	Sanford USD Medical Center	Sioux Falls	South Dakota
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	UCSD Medical Center - Vista	Vista	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Japan,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Dose-Limiting Toxicities (DLT)	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).	First 8 weeks of treatment (Combination A-D) First 4 weeks of treatment (CombinationF)
Primary	Objective Response - Number of Participants With Objective Response	For Phase 2: Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1).	Baseline up to approximately 24 months
Secondary	Cmax of avelumab (MSB0010718C)	Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)	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
Secondary	Cmax of PF-05082566	Cmax defined as the maximum plasma concentration of PF-05082566	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
Secondary	Ctrough of avelumab (MSB0010718C)	Ctrough is defined as the trough plasma concentration at the end of an avelumab dosage interval.	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
Secondary	Ctrough of PF-05082566	Ctrough is defined as the trough plasma concentration at the end of a PF-05082566 dosage interval.	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
Secondary	Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C)	Immunogenicity assessment of avelumab (MSB0010718C).	Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Secondary	Anti-Drug Antibody (ADA) levels of PF-05082566	Immunogenicity assessment of PF-05082566.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, and 12
Secondary	Time to Tumor Response (TTR)	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.	Baseline up to approximately 24 months
Secondary	Duration of Response (DR)	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.	Baseline up to approximately 24 months
Secondary	Progression-Free Survival (PFS)	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.	Baseline up to approximately 24 months
Secondary	Overall Survival (OS)	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.	Baseline up to approximately 24 months
Secondary	Tumor tissue biomarkers	Tumor tissue biomarkers, including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes	Baseline
Secondary	Cmax of PF-04518600	Cmax defined as the maximum plasma concentration of PF-04518600	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
Secondary	Anti-Drug Antibody (ADA) levels of PF-04518600	Immunogenicity assessment of PF-04518600.	Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Secondary	Ctrough of PF-04518600	Ctrough is defined as the trough plasma concentration at the end of a PF-04518600 dosage interval.	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

External Links

•   To obtain contact information for a study center near you, click here.