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Sintilimab Plus Axitinib for Advanced Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Phase 2 Nonrandomized

Xingming Zhang1, Haoyang Liu1, Jiayu Liang1

  • 1Department of Urology, Institute of Urology, Sichuan Clinical Research Center for Kidney and Urologic Diseases, West China Hospital, Sichuan University, Chengdu, China.

JAMA Oncology
|August 14, 2025
PubMed
Abstract

Insights

Sintilimab plus axitinib showed a 56% objective response rate and 19.8-month progression-free survival in advanced fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) patients. This combination therapy offers a promising, manageable treatment option for this lethal kidney cancer.

Area of Science:

  • Oncology
  • Nephrology
  • Immunotherapy

Background:

  • Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is an aggressive kidney cancer with limited treatment options.
  • Novel therapeutic strategies are urgently needed to improve outcomes for patients with advanced FH-deficient RCC.

Purpose of the Study:

  • To evaluate the efficacy and safety of combining sintilimab (an immune checkpoint inhibitor) with axitinib (a tyrosine kinase inhibitor) for advanced FH-deficient RCC.
  • To assess objective response rate (ORR) and progression-free survival (PFS) as primary endpoints.

Main Methods:

  • A phase 2, multicenter, open-label, single-arm clinical trial enrolled 41 treatment-naive patients with advanced FH-deficient RCC.
  • Patients received sintilimab intravenously every 3 weeks plus axitinib orally twice daily until disease progression or toxicity.
  • Primary endpoints included ORR and PFS, with secondary endpoints assessing safety, overall survival, and disease control rate.

Main Results:

  • The objective response rate (ORR) was 56% (95% CI, 40%-72%), with a median duration of response not reached.
  • Median progression-free survival (PFS) was 19.8 months (95% CI, 10.9 months to NR).
  • Grade 3 or higher treatment-related adverse events occurred in 32% of patients, most commonly hypertriglyceridemia (7%).

Conclusions:

  • The combination of sintilimab and axitinib demonstrated encouraging efficacy, with high ORR and prolonged PFS in advanced FH-deficient RCC.
  • The treatment regimen showed a manageable safety profile, suggesting it is a viable therapeutic option.
  • Further validation in a randomized clinical trial is warranted to confirm these findings.

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