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

NCT ID: NCT02954991

Last Updated: 2024-04-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

161 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-07

Study Completion Date

2021-11-04

Brief Summary

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

Detailed Description

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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.

Conditions

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Carcinoma, Non-Small-Cell Lung

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Glesatinib and 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

Group Type EXPERIMENTAL

Glesatinib

Intervention Type DRUG

Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor

Nivolumab

Intervention Type DRUG

nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Sitravatinib and 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

Group Type EXPERIMENTAL

Sitravatinib

Intervention Type DRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.

Nivolumab

Intervention Type DRUG

nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Mocetinostat and 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

Group Type EXPERIMENTAL

Mocetinostat

Intervention Type DRUG

Mocetinostat is an HDAC inhibitor.

Nivolumab

Intervention Type DRUG

nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Interventions

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Glesatinib

Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor

Intervention Type DRUG

Sitravatinib

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.

Intervention Type DRUG

Mocetinostat

Mocetinostat is an HDAC inhibitor.

Intervention Type DRUG

Nivolumab

nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Intervention Type DRUG

Other Intervention Names

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MGCD265 MGCD516 MGCD01013 Opdivo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Yuma Regional Medical Center

Yuma, Arizona, United States

Site Status

Beverly Hills Cancer Center

Beverly Hills, California, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

University of California San Francisco Comprehensive Cancer Center

San Francisco, California, United States

Site Status

University of California Los Angeles - Torrance - Community Cancer Care

Santa Clarita, California, United States

Site Status

Rocky Mountain Cancer Centers - Denver - Midtown

Denver, Colorado, United States

Site Status

Baptist Health

Louisville, Kentucky, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Saint Francis Cancer Treatment Center

Grand Island, Nebraska, United States

Site Status

Oncology Hematology Care-Blue Ash

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Hematology Oncology Associates - Barnett Office

Medford, Oregon, United States

Site Status

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Texas Oncology - South Austin

Austin, Texas, United States

Site Status

USOR - Texas Oncology - Denison Cancer Center

Denison, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

Virginia Cancer Specialist

Fairfax, Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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MRTX-500

Identifier Type: -

Identifier Source: org_study_id

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