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

Phase 2TerminatedNCT02954991

Mirati Therapeutics Inc.161 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

161

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

GlesatinibDRUG

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

SitravatinibDRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.

MocetinostatDRUG

Mocetinostat is an HDAC inhibitor.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (25)

Outcomes

Primary Outcomes

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.

Time frame: Up to 40.6 months

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: Up to 43.8 months

Data from ClinicalTrials.gov

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