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

Mirati Therapeutics

Status and phase: Completed; Phase 1

Conditions: Clear-Cell Renal Cell Carcinoma

Treatments: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04518046

516-008

Details and patient eligibility

About

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 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Phase 1: Dose Escalation

Experimental group

Description:

Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.

Treatment:

Drug: Ipilimumab

Drug: Nivolumab

Drug: Sitravatinib

Phase 1b Dose Escalation Cohort A

Experimental group

Description:

Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment

Treatment:

Drug: Ipilimumab

Drug: Nivolumab

Drug: Sitravatinib

Phase 1b Dose Escalation Cohort B

Experimental group

Description:

Patients with favorable-risk RCC with clear cell component for first-line treatment.

Treatment:

Drug: Ipilimumab

Drug: Nivolumab

Drug: Sitravatinib