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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03906071
Recruitment Status : Recruiting
First Posted : April 8, 2019
Last Update Posted : September 9, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Non-Squamous Non-Small Cell Lung Cancer Biological: Nivolumab Drug: Sitravatinib Drug: Docetaxel Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 532 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Nivolumab and Sitravatinib
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
Nivolumab is an antibody directed at the programmed death receptor-1 (PD-1), blocking its interaction with PD-L1 and PD-L2.
Other Name: Opdivo

Drug: Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.
Other Name: MGCD516
Active Comparator: Docetaxel
Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks.
 Drug: Docetaxel
Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.
Other Name: Taxotere


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 36 Months ]
    OS is defined as time from date of randomization to date of death due to any cause


Secondary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: 36 Months ]
    Frequency of patients experiencing treatment-emergent AEs

  2. Objective Response Rate (ORR) [ Time Frame: 36 Months ]
    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

  3. Progression-Free Survival (PFS) [ Time Frame: 36 months ]
    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03906071


Contacts
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Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 (toll free) miratistudylocator@emergingmed.com

Locations
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Sponsors and Collaborators
Mirati Therapeutics Inc.
Bristol-Myers Squibb
Investigators
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Study Director: Ronald L. Shazer, MD, MBA Mirati Therapeutics Inc.
More Information
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Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03906071    
Other Study ID Numbers: 516-005
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirati Therapeutics Inc.:
Sitravatinib
Nivolumab
Docetaxel
Checkpoint inhibitor
 MGCD516
NSCLC
SAPPHIRE
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
 Bronchial Neoplasms
Docetaxel
Nivolumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological