Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02954991
• Other study ID #: MRTX-500
• Status: Terminated
• Phase: Phase 2
• Start date: November 7, 2016
• Est. completion date: November 4, 2021

Study information

• Verified date: April 2024
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.

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 information / eligibility

• Status: Terminated
• Enrollment: 161
• Est. completion date: November 4, 2021
• Est. primary completion date: November 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Glesatinib
Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor
• Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.
• Mocetinostat
Mocetinostat is an HDAC inhibitor.
• Nivolumab
nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Locations

Country	Name	City	State
United States	Texas Oncology - South Austin	Austin	Texas
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Oncology Hematology Care-Blue Ash	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	USOR - Texas Oncology - Denison Cancer Center	Denison	Texas
United States	Rocky Mountain Cancer Centers - Denver - Midtown	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	Saint Francis Cancer Treatment Center	Grand Island	Nebraska
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California San Diego	La Jolla	California
United States	Baptist Health	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Hematology Oncology Associates - Barnett Office	Medford	Oregon
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt University	Nashville	Tennessee
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of California San Francisco Comprehensive Cancer Center	San Francisco	California
United States	University of California Los Angeles - Torrance - Community Cancer Care	Santa Clarita	California
United States	Northwest Cancer Specialists, P.C.	Tualatin	Oregon
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	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.	Up to 40.6 months
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	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)
Secondary	Duration of Response (DOR)	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).	Up to 38.8 months
Secondary	Progression Free Survival (PFS)	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.	Up to 40.6 months
Secondary	Overall Survival (OS)	OS was defined as the time from first dose of study drug to the date of death due to any cause.	Up to 43.8 months
Secondary	Blood Plasma Concentrations	Predose (trough) concentrations for sitravatinib	Cycle 1 Day 1 through Cycle 5 Day 1