Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
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
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:
Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
Drug: Ipilimumab
Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody
Other Names:
|
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:
Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
Drug: Ipilimumab
Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody
Other Names:
|
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:
Drug: Nivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
Drug: Ipilimumab
Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 Criteria
Criteria
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.- 516-008