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

Mirati Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Sitravatinib; Drug: Mocetinostat; Drug: Glesatinib; Drug: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02954991

MRTX-500

Details and patient eligibility

About

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

Full 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.

Enrollment: 161 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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161 participants in 3 patient groups

Glesatinib and Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Nivolumab

Drug: Glesatinib

Sitravatinib and Nivolumab

Experimental group

Description:

Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week

Treatment:

Drug: Nivolumab

Drug: Sitravatinib

Mocetinostat and Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Nivolumab

Drug: Mocetinostat