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

Mirati Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Metastatic Non-Squamous Non-Small Cell Lung Cancer

Treatments: Drug: Sitravatinib; Drug: Docetaxel; Biological: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03906071

CA248-0001 (Other Identifier)

516-005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 577 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
• Receipt of at least one but not more than two prior treatment regimens in the advanced setting
• Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy followed by checkpoint inhibitor therapy)
• Most recent treatment regimen must have included a checkpoint inhibitor therapy with radiographic disease progression on or after treatment
• Candidate to receive docetaxel as second or third line therapy

Exclusion criteria

• Uncontrolled brain metastases
• Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
• Unacceptable toxicity with prior checkpoint inhibitor therapy
• Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy
• Impaired heart function

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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577 participants in 2 patient groups

Nivolumab and Sitravatinib

Experimental group

Description:

Nivolumab will be administered by intravenous infusion over 30 minutes at 240 mg every 2 weeks or at 480 mg every 4 weeks. Sitravatinib capsules will be administered orally, once daily.

Treatment:

Biological: Nivolumab

Drug: Sitravatinib

Docetaxel

Active Comparator group

Description:

Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks.

Treatment:

Drug: Docetaxel