Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.

Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).

Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).

Patients And Methods: Eligible patients had pathologically confirmed advanced ccRCC. Patients received fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg every 3 weeks in 3-week cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.

Results: By March 31, 2023, 42 patients (median age 58.9 years; 81.0% male) had been treated in the RCC cohort. Among treatment-naive patients (n = 22), confirmed ORR was 68.2% (95% confidence interval [CI] 45.1-86.1). The median progression-free survival (PFS) was not reached, and 18-month PFS rate was 59.4%. Among previously treated patients (n = 20), the confirmed ORR was 60.0% (95% CI 36.1-80.9), and the median PFS was 15.9 (95% CI 5.4-19.3) months. All patients had adverse events related to study treatment, 52.4% of which were grade ≥ 3 in severity. Treatment-related adverse events with an incidence of ≥ 40% included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia.

Conclusions: Fruquintinib plus sintilimab demonstrated promising efficacy in advanced ccRCC and was well tolerated. A phase III study (FRUSICA-02) using this combination regimen in patients with previously treated advanced ccRCC is ongoing.

Trial Registration Number: The study was registered with ClinicalTrials.gov (NCT03903705).