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

Sponsor
Mirati Therapeutics Inc. (Industry)
Overall Status
Enrolling by invitation
CT.gov ID
NCT04518046
Collaborator
(none)
92
1
3
31.6
2.9

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
92 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Aug 11, 2020
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Mar 31, 2023

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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

    2. 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

    3. 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 Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MD Anderson Houston Texas United States 77030

    Sponsors and Collaborators

    • Mirati Therapeutics Inc.

    Investigators

    • Study Director: Hirak Der-Torossian, MD, Mirati Therapeutics Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mirati Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT04518046
    Other Study ID Numbers:
    • 516-008
    First Posted:
    Aug 19, 2020
    Last Update Posted:
    Jan 25, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 25, 2022