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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Metastatic Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Drug: Sitravatinib
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab and Sitravatinib<br>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. | Biological: Nivolumab<br>* Nivolumab is an antibody directed at the programmed death receptor-1 (PD-1), blocking its interaction with PD-L1 and PD-L2.<br>* Other names: Opdivo;Drug: Sitravatinib<br>* Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.<br>* Other names: MGCD516;|
| Active Comparator: Docetaxel<br>Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks. | Drug: Docetaxel<br>* Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as time from date of randomization to date of death due to any cause | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Frequency of patients experiencing treatment-emergent AEs | 36 Months | 
| Objective Response Rate (ORR) | ORR defined as complete response (CR) or partial response (PR) per RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy | 36 Months | 
| Progression-Free Survival (PFS) | PFS is defined as the time from randomization to the date of the first documentation of objective disease progression or death due to any cause | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sitravatinib, Nivolumab, Docetaxel, Checkpoint inhibitor, MGCD516, NSCLC, SAPPHIRE