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

• ClinicalTrials.gov Identifier: NCT03906071
• Recruitment Status: Recruiting
• First Posted: April 8, 2019
• Last Update Posted: March 12, 2021
• Sponsor: Mirati Therapeutics Inc.
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Mirati Therapeutics Inc.

Tracking Information

• First Submitted Date: April 4, 2019
• First Posted Date: April 8, 2019
• Last Update Posted Date: March 12, 2021
• Actual Study Start Date: July 15, 2019
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2019)

Overall Survival (OS) [ Time Frame: 36 Months ]

OS is defined as time from date of randomization to date of death due to any cause

• Original Primary Outcome Measures (submitted: April 4, 2019): Overall Survival (OS) [ Time Frame: 36 Months ]

Current Secondary Outcome Measures (submitted: April 5, 2019)

• Adverse Events (AEs) [ Time Frame: 36 Months ]
  Frequency of patients experiencing treatment-emergent AEs
• 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
• 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

Original Secondary Outcome Measures (submitted: April 4, 2019)

• Adverse Events (AEs) [ Time Frame: 36 Months ]
• Objective Response Rate (ORR) [ Time Frame: 36 Months ]
• Duration of Response (DOR) [ Time Frame: 36 Months ]
• Clinical Benefit Rate (CBR) [ Time Frame: 36 Months ]
• Progression-Free Survival (PFS) [ Time Frame: 36 months ]
• Blood plasma concentration of MGCD516 (PK) [ Time Frame: 36 Months ]
• Patient Reported Outcome (PRO) [ Time Frame: 36 Months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Non-Squamous Non-Small Cell Lung Cancer

Intervention

• 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
• Drug: Docetaxel
  Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.
  Other Name: Taxotere

Study Arms

• 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.
  Interventions:

  • Biological: Nivolumab
  • Drug: Sitravatinib
• Active Comparator: Docetaxel
  Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks.
  Intervention: Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 21, 2020): 532
• Original Estimated Enrollment (submitted: April 4, 2019): 664
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Belgium, Canada, France, Germany, Hungary, Italy, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT03906071
• Other Study ID Numbers: 516-005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Mirati Therapeutics Inc.
• Study Sponsor: Mirati Therapeutics Inc.
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Ronald L. Shazer, MD, MBA; Mirati Therapeutics Inc.

• PRS Account: Mirati Therapeutics Inc.
• Verification Date: February 2021