SUPPORT HOTLINE (888) 901-2226
Donate Now

BRIEF TITLE: Avelumab (msb0010718c) In Combination With Other Cancer Immunotherapies In Patients With Advanced Malignancies

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


  • Org Study ID: B9991004
  • Secondary ID: 2015-002552-27,JAVELIN MEDLEY
  • NCT ID: NCT02554812
  • NCT Alias:
  • Sponsor: Pfizer - Industry
  • Source: Pfizer

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 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 Outcomes:

Primary Outcome 1 - Measure: Number of participants with Dose-Limiting Toxicities (DLT)

Primary Outcome 1 - Time Frame: First 8 weeks of treatment

Primary Outcome 2 - Measure: Objective Response - Number of Participants With Objective Response

Primary Outcome 2 - Time Frame: Baseline up to approximately 24 months

Condition:

  • Advanced Cancer

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.

- 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)
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Pfizer CT.gov Call Center

Role: Study Director

Affiliation: Pfizer

Overall Contact

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.

Locations

Facility Status Contact
UC San Diego Moores Cancer Center
La Jolla, California 92037-0845
United States
Recruiting
UC San Diego Medical Center La Jolla (Thornton Hospital)
La Jolla, California 92037
United States
Recruiting
UC San Diego Moores Cancer Center
La Jolla, California 92093
United States
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
Recruiting
Georgetown University Medical Center
Washington, District of Columbia 20007
United States
Recruiting
Mount Sinai Comprehensive Cancer Center - Aventura
Aventura, Florida 33180
United States
Recruiting
Mount Sinai Medical Center
Miami Beach, Florida 33140
United States
Recruiting
Florida Cancer Specialists
Sarasota, Florida 34232
United States
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
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
NYU Investigational Pharmacy
New York, New York 10016
United States
Recruiting
NYU Langone Medical Center
New York, New York 10016
United States
Recruiting
NYU Laura and Isaac Perlmutter Cancer Center
New York, New York 10016
United States
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
Southeastern Medical Oncology Center
Clinton, North Carolina 28328
United States
Recruiting
Southeastern Medical Oncology Center
Goldsboro, North Carolina 27534
United States
Recruiting
Southeastern Medical Oncology Center
Jacksonville, North Carolina 28546
United States
Recruiting
Southeastern Medical Oncology Center
Wilson, North Carolina 27893
United States
Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Recruiting
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania 15232
United States
Terminated
UPCI Investigational Drug Service
Pittsburgh, Pennsylvania 15232
United States
Terminated
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania 15232
United States
Terminated
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
Recruiting
The Sarah Cannon Research Institute / Tennessee Oncology, PLLC
Nashville, Tennessee 37203
United States
Recruiting
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204
United States
Recruiting
Vanderbilt Health Pharmacy One Hundred Oaks
Nashville, Tennessee 37204
United States
Recruiting
Henry-Joyce Cancer Clinic
Nashville, Tennessee 37232
United States
Recruiting
Vanderbilt University Oncology Pharmacy
Nashville, Tennessee 37232
United States
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
Recruiting
University of Washington
Seattle, Washington 98109
United States
Recruiting
Chris O'Brien Lifehouse Pharmacy
Camperdown, New South Wales 2050
Australia
Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales 2050
Australia
Recruiting
Macquarie University Hospital Pharmacy
Macquarie University, New South Wales 2109
Australia
Recruiting
Macquarie University
Macquarie University, New South Wales 2109
Australia
Recruiting
The Mater Hospital
North Sydney, New South Wales 2060
Australia
Recruiting
Melanoma Institute Australia
North Sydney, New South Wales 2065
Australia
Recruiting
Baxter Healthcare
Old Toongabie, New South Wales 2146
Australia
Recruiting
Brighton Medical Imaging
Brighton, Victoria 3186
Australia
Recruiting
Cabrini Hospital Brighton
Brighton, Victoria 3186
Australia
Recruiting
Austin Health
Heidelberg, Victoria 3084
Australia
Recruiting
Cabrini Hospital Malvern
Malvern, Victoria 3144
Australia
Recruiting
Cabrini Hospital
Malvern, Victoria 3144
Australia
Recruiting
Malvern Medical Imaging
Malvern, Victoria 3144
Australia
Recruiting
Pharmacy
Malvern, Victoria 3144
Australia
Recruiting
Macquarie Heart
New South Wales, 2109
Australia
Recruiting
Macquarie Medical Imaging
New South Wales, 2109
Australia
Recruiting
Cross Cancer Institute
Edmonton, Alberta T6G 1Z2
Canada
Recruiting
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia V5Z 4E6
Canada
Recruiting
The Ottawa Hospital Cancer Centre
Ottawa, Ontario K1H 8L6
Canada
Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario M5G 2M9
Canada
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
National Cancer Center Hospital East
Kashiwa, Chiba 277-8577
Japan
Recruiting
National Cancer Center Hospital
Chuo-ku, Tokyo 104-0045
Japan
Recruiting
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Szpital w Warszawie
Warszawa, Mazowieckie 02-781
Poland
Recruiting
Uniwersyteckie Centrum Kliniczne - Szpital
Gdansk, Pomorskie 80-214
Poland
Not yet recruiting
Uniwersyteckie Centrum Kliniczne - Szpital
Gdansk, Pomorskie 80-952
Poland
Not yet recruiting
Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
Poznan, Wielkopolskie 60-355
Poland
Not yet recruiting
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna
Poznan, Wielkopolskie 60-569
Poland
Not yet recruiting
SP ZOZ Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu im. Prof. Ludwika Bierkowskiego
Poznan, Wielkopolskie 60-631
Poland
Not yet recruiting
Med - Polonia Sp. z.o.o.
Poznan, Wielkopolskie 61-693
Poland
Not yet recruiting
Investigational Drug Services, National Taiwan University Hospital
Taipei, 100
Taiwan
Active, not recruiting
National Taiwan University Hospital
Taipei, 100
Taiwan
Active, not recruiting
Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Taiwan
Not yet recruiting
Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Taiwan
Not yet recruiting
The Royal Marsden Hospital
London, SW3 6JJ
United Kingdom
Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
United Kingdom
Recruiting
Sarah Cannon Research Institute UK
London, W1G 6AD
United Kingdom
Recruiting
The Harley Street Clinic
London, W1G 7LJ
United Kingdom
Recruiting
The Harley Street Clinic
London, W1G 8PP
United Kingdom
Recruiting