NCT03906071

Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

A Randomized Phase 3 Study of Sitravatinib in Combination With Nivolumab Versus Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy SAPPHIRE

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 577 (actual)
• Sponsor: Mirati Therapeutics Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.

Detailed description

Sitravatinib (MGCD516) is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, TAM (Tyro3, AXL, MERTK) family, VEGFR family, PDGFR family, KIT, FLT3, TRK family, RET, DDR2, and selected EPH family members. Nivolumab is a human IgG monoclonal antibody that binds to the PD-1 receptor and selectively blocks the interaction with its ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. RTKs have been implicated in mediating an immunosuppressive tumor microenvironment, which has emerged as a potential resistance mechanism to checkpoint inhibitor therapy. Inhibition of these RTKs by sitravatinib may augment anti-tumor immune response and improve outcomes by overcoming resistance to checkpoint inhibitor therapy.

Conditions

• Metastatic Non-Squamous Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Nivolumab	Nivolumab is an antibody directed at the programmed death receptor-1 (PD-1), blocking its interaction with PD-L1 and PD-L2.
DRUG	Sitravatinib	Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.
DRUG	Docetaxel	Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.

Timeline

• Start date: 2019-07-15
• Primary completion: 2023-03-20
• Completion: 2025-09-30
• First posted: 2019-04-08
• Last updated: 2025-10-21
• Results posted: 2024-06-25

Locations

261 sites across 12 countries: United States, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom

Regulatory

• FDA-regulated drug study