Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

Mirati Therapeutics

Status and phase: Completed; Phase 2

Conditions: Clear Cell Renal Cell Carcinoma

Treatments: Drug: Nivolumab; Drug: Sitravatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03680521

516-002

Details and patient eligibility

About

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Full description

Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of nivolumab.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Imaging results consistent with locally-advanced RCC
2. Candidate for partial or complete nephrectomy as part of treatment plan.
3. Measurable disease per RECIST version 1.1.
4. ECOG performance status 0 or 1.
5. Adequate bone marrow and organ function.

Exclusion criteria

1. Prior systemic anti-tumor treatment for RCC.
2. Patients who are receiving any other investigational agents.
3. Clinical status indicating that immediate surgery (within 6 weeks) is warranted regardless of whether neoadjuvant therapy is to be administered, as assessed by the treating surgeon.
4. Inability to undergo baseline tumor biopsy.
5. Active or prior documented autoimmune or immunocompromising conditions.
6. Uncontrolled hypertension.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Sitravatinib and nivolumab

Experimental group

Description:

Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.

Treatment:

Drug: Nivolumab

Drug: Sitravatinib