Clinical trial NCT02954991: Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer
Official title: A Parallel Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of non-small cell lung cancer.
* Prior treatment with a checkpoint inhibitor (as appropriate per cohort)
* Adequate bone marrow and organ function

Exclusion Criteria:

* Uncontrolled tumor in the brain
* Unacceptable toxicity with prior checkpoint inhibitor
* Impaired heart function

Primary outcomes:
measure: Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
timeFrame: Up to 40.6 months
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: Up to 38.8 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 40.6 months
measure: Overall Survival (OS)
timeFrame: Up to 43.8 months
measure: Blood Plasma Concentrations
timeFrame: Cycle 1 Day 1 through Cycle 5 Day 1
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Comprehensive Cancer Center
state: California
city: Santa Clarita
country: United States
facility: University of California Los Angeles - Torrance - Community Cancer Care
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver - Midtown
state: Colorado
city: Louisville
country: United States
facility: Baptist Health
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center
state: Nebraska
city: Cincinnati
country: United States
facility: Oncology Hematology Care-Blue Ash
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Medford
country: United States
facility: Hematology Oncology Associates - Barnett Office
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Denison
country: United States
facility: USOR - Texas Oncology - Denison Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
References: