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

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 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.

Study Overview

• Status: Completed
• Conditions: Clear-Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation; Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.	Drug: Sitravatinib; Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases; Other Names: MGCD516; Drug: Nivolumab; Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: OPDIVO; Drug: Ipilimumab; Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody; Other Names: YERVOY
Experimental: Phase 1b Dose Escalation Cohort A; Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment	Drug: Sitravatinib; Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases; Other Names: MGCD516; Drug: Nivolumab; Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: OPDIVO; Drug: Ipilimumab; Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody; Other Names: YERVOY
Experimental: Phase 1b Dose Escalation Cohort B; Patients with favorable-risk RCC with clear cell component for first-line treatment.	Drug: Sitravatinib; Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases; Other Names: MGCD516; Drug: Nivolumab; Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Names: OPDIVO; Drug: Ipilimumab; Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody; Other Names: YERVOY

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Curtis Chin, MD, Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: 516-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No