Sintilimab and axitinib combo shows promise in renal cell carcinoma subtype


The median progression-free survival with the combination was 19.83 months.

The combination of sintilimab injection (Tyvyt) and axitinib (Inlyta) demonstrated a manageable safety profile and initial anti-tumor efficacy in patients with fumarate hydratase-deficient renal cell carcinoma (FH-dRCC), according to data from a phase 2 study (NCT04387500) presented at the 2024 ASCO Annual Meeting.1

The trial's co-primary end points are the ORR per RECIST v1.1 and PFS.

The trial's co-primary end points are the ORR per RECIST v1.1 and PFS.

According to the authors, previous data has shown that immune checkpoint inhibitors (ICI) in combination with tyrosine kinase inhibitors (TKI) may be used as front-line treatment for patients with FH-dRCC. To that end, the current study sought to assess the initial efficacy and safety of sintilimab, a PD-1 inhibitor, in combination with axitinib, a TKI, in this patient population.

In total, the study enrolled 41 patients with advanced FH-dRCC. Among the 38 patients eligible for the efficacy analysis, 10.5% (4/38) of patients achieved a confirmed complete response. On the study’s co-primary end points, the objective response rate (ORR) was 60.5% (23/38), and the median progression-free survival (PFS) was 19.83 months (95% CI, 7.68-31.99). The study additionally reported a disease-controlled rate (DCR) of 86.8%.

The authors also noted, “Details about FH mutation status were available in 40 patients, and different FH mutation patterns were found to be associated with different therapeutic efficacy.”

Regarding safety, 87.8% of patients (36/41) experienced a treatment-emergent adverse event (TEAE) of any grade, and 22.0% of patients (9/41) experienced a TEAE of grade 3 or higher.

Overall, the investigator-initiated, open-label, single-arm, multi-institutional, phase 2 study enrolled adult patients with treatment naïve, advanced FH-dRCC from June 2021 to August 2023. Overall, 52 patients were screened, and 41 patients were enrolled in the trial.

To be included in the study, patients needed to have RCC as confirmed by histopathology, a life expectancy of 3 months or longer, and adequate organ and bone marrow function. Additionally, patients could not have received prior treatment with systemic therapy or targeted drugs.2

Those enrolled in the trial received first-line treatment with sintilimab via intravenous injection every 3 weeks plus 5 mg oral axitinib taken twice daily until disease progression or intolerant to treatment. The median follow-up among all patients was 16.0 months.

The primary end points for the study are the ORR per RECIST v1.1 and PFS, both of which may be assessed up to 3 years. Secondary end points for the trial include overall survival, DCR, and duration of response. The number of patients who experience TEAEs is an additional end point of interest.

The phase 2 trial remains ongoing, with expected completion in January 2026.

Overall, the authors concluded, “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.”


1. Zeng H, Zhang X, Liang J, et al. Sintilimab plus axitinib for advanced fumarate hydratase-deficient renal cell carcinoma: A multi-center, open-label, single-arm, phase II study (SAFH). 2024;42 (suppl 16).

2. Sintilimab injection combined with inlyta in fumarate hydratase- deficient renal cell carcinoma. Last updated April 9, 2024. Accessed June 12, 2024.

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