Sintilimab plus axitinib for advanced fumarate hydratase-deficient renal cell carcinoma: A multi-center, open-label, single-arm, phase II study (SAFH).

4523 Background: Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a rare and highly invasive subtype of renal cell carcinoma. Previous studies have shown that immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) can be considered for first-line systemic treatment of FH-dRCC. We aimed to provide high-quality prospective clinical trial evidence regarding the efficacy and safety of Sintilimab plus Axitinib in FH-dRCC. Methods: This study was an investigator-initiated, open-label, single-arm, multiple institutional, phase II trial in patients (pts) aged 18 years or older with treatment naive, advanced FH-dRCC. Patients received Sintilimab (intravenous injection, every 3 week) in combination with Axitinib (5mg, orally taken per day) as first-line treatment until disease progression or intolerant to treatment. The primary endpoint was objective response rate (ORR; RECIST v1.1) and progression-free survival (PFS). This study is registered with ClinicalTrials.gov, NCT04387500. Results: From June 2021 to August 2023, 52 patients were screened, and 41 patients were enrolled. The median follow up was 16.0 months. Thirty-eight patients were available for efficacy assessment. Confirmed complete response rate was 10.5% (4/38), ORR was 60.5% (23/38). Disease-controlled rate (DCR) was 86.8%. The median PFS was 19.83 months (95% CI: 7.68-31.99). All grade and ≥3 treatment-emergent adverse events occurred in 87.8% (36/41) and 22.0% (9/41), respectively. Details about FH mutation status were available in 40 patients, and different FH mutation patterns were found to be associated with different therapeutic efficacy. Conclusions: The combination of Sintilimab and Axitinib showed manageable safety profile and durable anti-tumor efficacy in FH-dRCC. Evaluating mutation status of FH gene could help to predict potential survival benefit from ICI plus TKI therapy. Clinical trial information: NCT04387500 .