A Phase Ib/II clinical trial evaluating the combination of fruquintinib and sintilimab has shown promising results in patients with advanced clear cell renal cell carcinoma (ccRCC), both in treatment-naive and previously treated settings. The study, conducted in China, assessed the efficacy and safety of this combination, which leverages the synergistic antitumor activity of antiangiogenic inhibitors and immune checkpoint inhibitors.
The trial enrolled patients with pathologically confirmed advanced ccRCC who received fruquintinib (5 mg once daily, 2 weeks on/1 week off) plus sintilimab (200 mg every 3 weeks). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Objective Response and Survival Outcomes
As of March 31, 2023, 42 patients were treated in the RCC cohort. Among the treatment-naive patients (n = 22), the confirmed ORR was 68.2% (95% CI: 45.1-86.1). The median progression-free survival (PFS) was not reached, and the 18-month PFS rate was 59.4%. In the previously treated group (n = 20), the confirmed ORR was 60.0% (95% CI: 36.1-80.9), with a median PFS of 15.9 months (95% CI: 5.4-19.3).
Safety and Tolerability
All patients experienced adverse events related to the study treatment, with 52.4% being grade ≥ 3 in severity. Common treatment-related adverse events (≥ 40% incidence) included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia. These adverse events were generally manageable, indicating that the combination is reasonably well-tolerated.
Ongoing Phase III Trial
These encouraging results have led to an ongoing Phase III study (FRUSICA-02) further evaluating this combination regimen in patients with previously treated advanced ccRCC. This trial aims to confirm the benefits observed in the Phase Ib/II study and potentially establish a new treatment option for this patient population.
The study is registered with ClinicalTrials.gov (NCT03903705).
