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

NCT ID: NCT04518046

Last Updated: 2024-06-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-11

Study Completion Date

2023-06-30

Brief Summary

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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

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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.

Conditions

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Clear-Cell Renal Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Following the identification of the recommended dose of sitravatinib in combination with NIVO/IPI Phase 1 dose escalation, two Phase 1b dose expansion cohorts will enroll patients with ccRCC based on IMDC risk. All patients receive the same treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1: Dose Escalation

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

Group Type EXPERIMENTAL

Sitravatinib

Intervention Type DRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Nivolumab

Intervention Type DRUG

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Ipilimumab

Intervention Type DRUG

Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

Phase 1b Dose Escalation Cohort A

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

Group Type EXPERIMENTAL

Sitravatinib

Intervention Type DRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Nivolumab

Intervention Type DRUG

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Ipilimumab

Intervention Type DRUG

Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

Phase 1b Dose Escalation Cohort B

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

Group Type EXPERIMENTAL

Sitravatinib

Intervention Type DRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Nivolumab

Intervention Type DRUG

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Ipilimumab

Intervention Type DRUG

Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

Interventions

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Sitravatinib

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Intervention Type DRUG

Nivolumab

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

Intervention Type DRUG

Ipilimumab

Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody

Intervention Type DRUG

Other Intervention Names

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MGCD516 OPDIVO YERVOY

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Curtis Chin, MD

Role: STUDY_DIRECTOR

Mirati Therapeutics Inc.

Locations

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MD Anderson

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39794332 (View on PubMed)

Other Identifiers

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516-008

Identifier Type: -

Identifier Source: org_study_id

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