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

Overview

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.

Full Title of Study: “A Phase 1/1b Study of Sitravatinib in Combination With Nivolumab and Ipilimumab in Patients With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 30, 2023

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.

Interventions

  • Drug: Sitravatinib
    • Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
  • Drug: Nivolumab
    • Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
  • Drug: Ipilimumab
    • Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

Arms, Groups and Cohorts

  • Experimental: Phase 1: Dose Escalation
    • Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
  • Experimental: Phase 1b Dose Escalation Cohort A
    • Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
  • Experimental: Phase 1b Dose Escalation Cohort B
    • Patients with favorable-risk RCC with clear cell component for first-line treatment.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Objective Response Rate (ORR) in accordance with RECIST v1.1
    • Time Frame: Through duration of study, average of 10 months
    • Frequency of patients experiencing an objective response
  • Duration of Response (DOR)
    • Time Frame: 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
  • Progression-free Survival (PFS)
    • Time Frame: 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mirati Therapeutics Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Curtis Chin, MD, Study Director, Mirati Therapeutics Inc.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.