Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies

Phase 1

Completed

• Conditions: Clear-Cell Renal Cell Carcinoma
• Interventions: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab

• Registration Number: NCT04518046
• Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary

Study 516-008 is an open-label Phase 1 dose escalation/Phase 1b dose expansion study evaluating the safety and tolerability, clinical activity, and PK of sitravatinib in combination with nivolumab and ipilimumab for the treatment of ccRCC and potentially other solid tumor types.

Detailed Description

Sitravatinib is a spectrum-selective receptor tyrosine kinase (RTK) inhibitor that inhibits several closely related RTKs including the TAM family (Tyro3/Axl/MERTK), VEGFR2, KIT, and MET.

NIVO/IPI are monoclonal antibodies (mAbs) that inhibit the immune checkpoint proteins programmed death receptor-1 (PD-1) and cytotoxic T- lymphocyte antigen-4 (CTLA-4), respectively.

The current study is designed to evaluate the triple combination of sitravatinib plus NIVO/IPI in patients with solid tumor malignancies that have shown favorable responses to NIVO/IPI combinations in previous clinical trials. Combining sitravatinib and NIVO/IPI is predicted to have complementary effects in triggering a tumor-directed immune response.

Study Timeline

• Study First Submitted: 2020-08-03
• Study Start: 2020-08-11
• Study First Submitted QC: 2020-08-14
• Study First Posted: 2020-08-19
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Confirmed diagnosis of Clear-Cell Renal Cell Carcinoma (for initial cohorts under consideration)
• No prior treatment with systemic therapy (for initial cohorts under consideration)
• Adequate bone marrow and organ function

Exclusion Criteria

• Known or suspected presence of other cancer
• Brain metastases (for initial cohorts under consideration)
• Carcinomatous meningitis
• Immunocompromising conditions
• Impaired heart function
• Active or prior documented autoimmune disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b Dose Escalation Cohort B	Sitravatinib	Patients with favorable-risk RCC with clear cell component for first-line treatment.
Phase 1: Dose Escalation	Sitravatinib	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
Phase 1: Dose Escalation	Nivolumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
Phase 1: Dose Escalation	Ipilimumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
Phase 1b Dose Escalation Cohort A	Sitravatinib	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
Phase 1b Dose Escalation Cohort A	Nivolumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
Phase 1b Dose Escalation Cohort B	Ipilimumab	Patients with favorable-risk RCC with clear cell component for first-line treatment.
Phase 1b Dose Escalation Cohort A	Ipilimumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
Phase 1b Dose Escalation Cohort B	Nivolumab	Patients with favorable-risk RCC with clear cell component for first-line treatment.

Primary Outcome Measures

Name	Time	Method
Frequency of patients experiencing treatment-emergent AEs	Through study completion, an average of 12 months	Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Through duration of study, average of 10 months	Time from date of first study treatment to first PD or death due to any cause in the absence of documented PD
Objective Response Rate (ORR) in accordance with RECIST v1.1	Through duration of study, average of 10 months	Frequency of patients experiencing an objective response
Duration of Response (DOR)	Through duration of study, average of 10 months	Time in months from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective PD or to death due to any cause in the absence of documented PD

Trial Locations

Locations (1)

MD Anderson; 🇺🇸 Houston, Texas, United States