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.
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.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | November 9, 2015 | Phase 2 | Interventional |
Primary Outcome 1 - Measure: Number of participants with Dose-Limiting Toxicities (DLT)
Primary Outcome 1 - Time Frame: First 8 weeks of treatment (Combination A-D) First 4 weeks of treatment (CombinationF)
Primary Outcome 2 - Measure: Objective Response - Number of Participants With Objective Response
Primary Outcome 2 - Time Frame: Baseline up to approximately 24 months
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 (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)
Show More
Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Pfizer CT.gov Call Center
Role: Study Director
Affiliation: Pfizer
Name: Pfizer CT.gov Call Center
Phone: 1-800-718-1021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Link: To obtain contact information for a study center near you, click here.
Facility | Status | Contact |
---|---|---|
UCSD Medical Center - Encinitas Encinitas, California 92024 United States |
Active, not recruiting | |
Koman Family Outpatient Pavilion La Jolla, California 92037 United States |
Active, not recruiting | |
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital) La Jolla, California 92037 United States |
Active, not recruiting | |
UC San Diego Perlman Medical Offices La Jolla, California 92037 United States |
Active, not recruiting | |
UC San Diego Moores Cancer Center La Jolla, California 92093 United States |
Active, not recruiting | |
UCLA Clinical Research Unit (Adminstration Office) Los Angeles, California 90024 United States |
Recruiting | |
Ronald Reagan UCLA Medical Center Los Angeles, California 90095 United States |
Recruiting | |
UCLA Hematology-Oncology Clinic Los Angeles, California 90095 United States |
Recruiting | |
UCLA Hematology-Oncology Infusion Center Los Angeles, California 90095 United States |
Recruiting | |
UC San Diego Medical Center - Hillcrest San Diego, California 92103 United States |
Active, not recruiting | |
UCSD Medical Center - Vista Vista, California 92081 United States |
Active, not recruiting | |
Georgetown University Medical Center Washington, District of Columbia 20007 United States |
Recruiting | |
Mount Sinai Comprehensive Cancer Center - Aventura Aventura, Florida 33180 United States |
Active, not recruiting | |
Mount Sinai Comprehensive Cancer Center Miami Beach, Florida 33140 United States |
Active, not recruiting | |
Florida Cancer Specialists Sarasota, Florida 34232 United States |
Active, not recruiting | |
H Lee Moffitt Cancer Center and Research Institute Tampa, Florida 33612 United States |
Recruiting | |
University of Iowa Hospitals and Clinics Iowa City, Iowa 52242 United States |
Recruiting | |
Norton Cancer Institute - Downtown Louisville, Kentucky 40202 United States |
Not yet recruiting | |
Norton Cancer Institute Downtown Louisville, Kentucky 40202 United States |
Not yet recruiting | |
Norton Hospital Louisville, Kentucky 40202 United States |
Not yet recruiting | |
Norton Brownsboro Hospital Louisville, Kentucky 40241 United States |
Not yet recruiting | |
Norton Cancer Institute, Brownsboro Hospital Campus, Louisville, Kentucky 40241 United States |
Not yet recruiting | |
University of Michigan Hospitals Ann Arbor, Michigan 48109-5008 United States |
Recruiting | |
University of Michigan Ann Arbor, Michigan 48109 United States |
Recruiting | |
Investigational Pharmacy, Karmanos Cancer Center Detroit, Michigan 48201 United States |
Recruiting | |
Karmanos Cancer Institute Detroit, Michigan 48201 United States |
Recruiting | |
Karmanos Cancer Institute Weisberg Cancer Treatment Center Farmington Hills, Michigan 48334 United States |
Recruiting | |
Northville Health Center Northville, Michigan 48168 United States |
Recruiting | |
VA NY Harbor Healthcare System New York, New York 10010 United States |
Active, not recruiting | |
NYU Investigational Pharmacy New York, New York 10016 United States |
Active, not recruiting | |
NYU Langone Medical Center New York, New York 10016 United States |
Active, not recruiting | |
NYU Laura and Isaac Perlmutter Cancer Center New York, New York 10016 United States |
Active, not recruiting | |
Weill Cornell Medical College New York, New York 10021 United States |
Recruiting | |
Breast Center at Weill Cornell Medicine New York, New York 10065 United States |
Recruiting | |
Research Pharmacy #PH# New York, New York 10065 United States |
Recruiting | |
Weill Cornell Medical College/New York Presbyterian Hospital New York, New York 10065 United States |
Recruiting | |
Sampson Regional Medical Center Clinton, North Carolina 28328 United States |
Active, not recruiting | |
Southeastern Medical Oncology Center Clinton, North Carolina 28328 United States |
Active, not recruiting | |
Southeastern Medical Oncology Center Goldsboro, North Carolina 27534 United States |
Active, not recruiting | |
Wayne Memorial Hospital Goldsboro, North Carolina 27534 United States |
Active, not recruiting | |
Onslow Memorial Hospital Jacksonville, North Carolina 28546 United States |
Active, not recruiting | |
Southeastern Medical Oncology Center Jacksonville, North Carolina 28546 United States |
Active, not recruiting | |
Fox Chase Cancer Center Philadelphia, Pennsylvania 19111 United States |
Active, not recruiting | |
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania 15232 United States |
Terminated | |
UPCI Investigational Drug Service Pittsburgh, Pennsylvania 15232 United States |
Terminated | |
UPMC Hillman Cancer Center Investigational Drug Service Pharmacy Pittsburgh, Pennsylvania 15232 United States |
Not yet recruiting | |
UPMC Hillman Cancer Center Pittsburgh, Pennsylvania 15232 United States |
Not yet recruiting | |
UPMC Shadyside Hospital Pittsburgh, Pennsylvania 15232 United States |
Terminated | |
UPMC Shadyside Hospital Pittsburgh, Pennsylvania 15232 United States |
Not yet recruiting | |
Rhode Island Hospital Providence, Rhode Island 02903 United States |
Recruiting | |
Miriam Hospital Providence, Rhode Island 02906 United States |
Recruiting | |
Sanford Cancer Center Oncology Clinic & Pharmacy Sioux Falls, South Dakota 57104 United States |
Recruiting | |
Sanford Gynecologic Oncology Clinic Sioux Falls, South Dakota 57104 United States |
Recruiting | |
Sanford Research Sioux Falls, South Dakota 57104 United States |
Recruiting | |
Sanford USD Medical Center Sioux Falls, South Dakota 57105 United States |
Recruiting | |
Tennessee Oncology, PLLC Nashville, Tennessee 37203 United States |
Active, not recruiting | |
The Sarah Cannon Research Institute / Tennessee Oncology, PLLC Nashville, Tennessee 37203 United States |
Active, not recruiting | |
Henry-Joyce Cancer Clinic Nashville, Tennessee 37232 United States |
Active, not recruiting | |
Vanderbilt University Oncology Pharmacy Nashville, Tennessee 37232 United States |
Active, not recruiting | |
University of Texas Southwestern Medical Center Dallas, Texas 75390 United States |
Recruiting | |
UT Southwestern Simmons Comprehensive Cancer Center Dallas, Texas 75390 United States |
Recruiting | |
The University of Texas MD Anderson Cancer Center Houston, Texas 77030 United States |
Recruiting | |
Seattle Cancer Care Alliance Seattle, Washington 98109 United States |
Active, not recruiting | |
University of Washington Medical Center Seattle, Washington 98195 United States |
Active, not recruiting | |
Chris O'Brien Lifehouse Camperdown, New South Wales 2050 Australia |
Active, not recruiting | |
Macquarie University Hospital Pharmacy Macquarie University, New South Wales 2109 Australia |
Active, not recruiting | |
Macquarie University Macquarie University, New South Wales 2109 Australia |
Active, not recruiting | |
Melanoma Institute Australia North Sydney, New South Wales 2060 Australia |
Recruiting | |
The Mater Hospital North Sydney, New South Wales 2060 Australia |
Recruiting | |
Baxter Healthcare Old Toongabie, New South Wales 2146 Australia |
Recruiting | |
Brighton Medical Imaging Brighton, Victoria 3186 Australia |
Active, not recruiting | |
Cabrini Hospital Brighton Brighton, Victoria 3186 Australia |
Active, not recruiting | |
Austin Health Heidelberg, Victoria 3084 Australia |
Active, not recruiting | |
Cabrini Hospital Malvern Malvern, Victoria 3144 Australia |
Active, not recruiting | |
Cabrini Hospital Malvern, Victoria 3144 Australia |
Active, not recruiting | |
Malvern Medical Imaging Malvern, Victoria 3144 Australia |
Active, not recruiting | |
Macquarie Heart New South Wales, 2109 Australia |
Active, not recruiting | |
Macquarie Medical Imaging New South Wales, 2109 Australia |
Active, not recruiting | |
Cross Cancer Institute Edmonton, Alberta T6G 1Z2 Canada |
Active, not recruiting | |
British Columbia Cancer Agency - Vancouver Centre Vancouver, British Columbia V5Z 4E6 Canada |
Active, not recruiting | |
The Ottawa Hospital Cancer Centre Ottawa, Ontario K1H 8L6 Canada |
Recruiting | |
Princess Margaret Cancer Centre Toronto, Ontario M5G 2M9 Canada |
Active, not recruiting | |
PH 145294, Centre Hospitalier de l'Université de Montréal (CHUM) Montreal, Quebec H2X 0C2 Canada |
Recruiting | |
Centre Hospitalier de l'Université de Montréal (CHUM) Montreal, Quebec H2X 3E4 Canada |
Recruiting | |
Institut Gustave Roussy Villejuif, Cedex 94805 France |
Active, not recruiting | |
Institut Gustave Roussy Villejuif, 94805 France |
Active, not recruiting | |
National Cancer Center Hospital East Kashiwa, Chiba 277-8577 Japan |
Active, not recruiting | |
National Cancer Center Hospital Chuo-ku, Tokyo 104-0045 Japan |
Active, not recruiting | |
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa, Mazowieckie 02-781 Poland |
Active, not recruiting | |
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa, 02-781 Poland |
Active, not recruiting | |
Investigational Drug Services, National Taiwan University Hospital Taipei, 100 Taiwan |
Active, not recruiting | |
National Taiwan University Hospital Taipei, 100 Taiwan |
Active, not recruiting | |
The Royal Marsden Hospital London, SW3 6JJ United Kingdom |
Active, not recruiting | |
The Royal Marsden NHS Foundation Trust London, SW3 6JJ United Kingdom |
Active, not recruiting | |
Sarah Cannon Research Institute UK London, W1G 6AD United Kingdom |
Active, not recruiting | |
The Harley Street Clinic London, W1G 7LJ United Kingdom |
Active, not recruiting | |
The Harley Street Clinic London, W1G 8PP United Kingdom |
Active, not recruiting |