Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT02954991
- Lead Sponsor
- Mirati Therapeutics Inc.
- Brief Summary
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.
- Detailed Description
Glesatinib is an orally administered multi-targeted tyrosine kinase inhibitor (TKI) that primarily targets the Axl and Mesenchymal-Epithelial Transition (MET) receptors. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone.
The study will begin with a lead-in dose escalation evaluation of two dose levels of each investigational agent in combination with nivolumab. Following completion of the lead-in dose escalation, enrollment into the Phase 2 study will proceed.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 161
- Diagnosis of non-small cell lung cancer.
- Prior treatment with a checkpoint inhibitor (as appropriate per cohort)
- Adequate bone marrow and organ function
- Uncontrolled tumor in the brain
- Unacceptable toxicity with prior checkpoint inhibitor
- Impaired heart function
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glesatinib and Nivolumab Glesatinib Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Glesatinib and Nivolumab Nivolumab Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Sitravatinib and Nivolumab Sitravatinib Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Sitravatinib and Nivolumab Nivolumab Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Mocetinostat and Nivolumab Nivolumab Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Mocetinostat and Nivolumab Mocetinostat Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Up to 40.6 months ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs) Day 1 up to 28 days after the last dose (median time on treatment was: CIT experienced 3.7 months; CIT naïve 4.8 months) TEAEs were defined as any event that first occur or increase in severity on or after the first dose of study treatment and not more than 28 days after the last dose of study treatment and prior to the initiation of subsequent systemic anti- cancer therapy.
Any clinically significant changes in laboratory tests were recorded as TEAEs.Duration of Response (DOR) Up to 38.8 months DOR was defined as the time in months from date of the first documentation of objective response (CR or PR) to the first documentation of objective progressive disease (PD) or to death due to any cause in the absence of documented PD. (Be aware, the population analyzed here is the Clinical Activity Evaluable Population and not the Full Analysis Set as used in outcome measure 1).
Progression Free Survival (PFS) Up to 40.6 months PFS was defined as the time from the first dose of study drug to the date of PD or death due to any cause in the absence of documented PD, whichever occurs first.
Overall Survival (OS) Up to 43.8 months OS was defined as the time from first dose of study drug to the date of death due to any cause.
Blood Plasma Concentrations Cycle 1 Day 1 through Cycle 5 Day 1 Predose (trough) concentrations for sitravatinib
Trial Locations
- Locations (25)
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
USOR - Texas Oncology - Denison Cancer Center
🇺🇸Denison, Texas, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Oncology Hematology Care-Blue Ash
🇺🇸Cincinnati, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of California San Francisco Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
University of California Los Angeles - Torrance - Community Cancer Care
🇺🇸Santa Clarita, California, United States
Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Hematology Oncology Associates - Barnett Office
🇺🇸Medford, Oregon, United States
Northwest Cancer Specialists, P.C.
🇺🇸Tualatin, Oregon, United States
Texas Oncology - South Austin
🇺🇸Austin, Texas, United States
Virginia Cancer Specialist
🇺🇸Fairfax, Virginia, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Baptist Health
🇺🇸Louisville, Kentucky, United States
Rocky Mountain Cancer Centers - Denver - Midtown
🇺🇸Denver, Colorado, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States