Clinical trial NCT04518046: Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clear-Cell Renal Cell Carcinoma
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Frequency of patients experiencing treatment-emergent AEs
timeFrame: Through study completion, an average of 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR) in accordance with RECIST v1.1
timeFrame: Through duration of study, average of 10 months
measure: Duration of Response (DOR)
timeFrame: Through duration of study, average of 10 months
measure: Progression-free Survival (PFS)
timeFrame: Through duration of study, average of 10 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson
state: Texas
Study officials:
affiliation: Mirati Therapeutics Inc.
name: Curtis Chin, MD
role: STUDY_DIRECTOR
References: