Clear-Cell Renal Cell Carcinoma
Conditions
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.
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.
Interventions
DRUGSitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
DRUGNivolumab
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
DRUGIpilimumab
Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed