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

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

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

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Sitravatinib; Drug: Glesatinib; Drug: Nivolumab; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • San Francisco, California, United States, 94115
      • University of California San Francisco Comprehensive Cancer Center
    • Santa Clarita, California, United States, 91355
      • University of California Los Angeles - Torrance - Community Cancer Care
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers - Denver - Midtown
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Health
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A.
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care-Blue Ash
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Hematology Oncology Associates - Barnett Office
    • Tualatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, P.C.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology - South Austin
    • Denison, Texas, United States, 75020
      • USOR - Texas Oncology - Denison Cancer Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Glesatinib; Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor; Other Names: MGCD265; Drug: Nivolumab; nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: Opdivo
Experimental: 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	Drug: Sitravatinib; Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.; Other Names: MGCD516; Drug: Nivolumab; nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: Opdivo
Experimental: 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	Drug: Nivolumab; nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: Opdivo; Drug: Mocetinostat; Mocetinostat is an HDAC inhibitor.; Other Names: MGCD01013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
Blood Plasma Concentrations	Predose (trough) concentrations for sitravatinib	Cycle 1 Day 1 through Cycle 5 Day 1

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2016
• Primary Completion (Actual): November 4, 2021
• Study Completion (Actual): November 4, 2021

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimated): November 4, 2016

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Histone Deacetylase Inhibitors; Nivolumab; Mocetinostat
• Other Study ID Numbers: MRTX-500

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO