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

NCT04518046 — Phase 1, Completed, 22 participants, Mirati Therapeutics Inc.

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

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

Registry	NCT04518046
Status	Completed
Phase	Phase 1
Study type	Interventional; non randomized, sequential, masking: none, treatment
Enrollment	22 (Actual)
Sponsor	Mirati Therapeutics Inc. (Industry)
Conditions	Clear-Cell Renal Cell Carcinoma
Interventions	Sitravatinib, Nivolumab, Ipilimumab (Drug)
Dates	start 2020-08-11, primary completion 2023-06-30, completion 2023-06-30, first posted 2020-08-19, last updated 2024-06-05
Locations	1 site in United States

-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.

Expand all sections · Collapse all

+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.

+Arms and interventions

Arm	Type	Interventions	Description
Phase 1: Dose Escalation	Experimental	Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
Phase 1b Dose Escalation Cohort A	Experimental	Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab	Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
Phase 1b Dose Escalation Cohort B	Experimental	Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab	Patients with favorable-risk RCC with clear cell component for first-line treatment.

Sitravatinib (Drug), also known as MGCD516: Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Nivolumab (Drug), also known as OPDIVO: Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Ipilimumab (Drug), also known as YERVOY: Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

+Outcome measures

Primary outcomes

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 outcomes

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
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

+Eligibility

Sex: All, ages: 18 Years to any

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

+Locations (1)

Facility	City	Country	Status
MD Anderson	Houston, Texas	United States

+Publications

Results publication: Msaouel P, Yu K, Yuan Y, Chen J, Yan X, Karki M, Duan F, Sheth RA, Rao P, Sircar K, Shah AY, Zurita AJ, Genovese G, Li M, Yeh CC, Dang M, Han G, Chu Y, Hallin M, Olson P, Yang R, Slavin D, Der-Torossian H, Chin CD, Tannir NM, Wang L, Gao J. Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial. Nat Commun. 2025 Jan 10;16(1):578. doi: 10.1038/s41467-024-55642-8. PMID 39794332

+Investigators

Curtis Chin, MD, Study director, Mirati Therapeutics Inc.