Fruquintinib/Sintilimab Meets PFS End Point in Advanced or Metastatic RCC

Fruquintinib plus sintilimab improved PFS, ORR, and DOR compared with axitinib or everolimus monotherapy in RCC in the phase 2/3 FRUSICA-2 trial.

Fruquintinib (Elunate) plus sintilimab (Tyvyt) met its primary end point of progression-free survival (PFS) in the second-line treatment of patients with locally advanced or metastatic renal cell carcinoma (RCC) in the phase 2/3 FRUSICA-2 trial (NCT05522231), according to a press release from the developers, HUTCHMED and Innovent Biologics.¹

The treatment combination also showed improvements in objective response rate (ORR) and duration of response (DOR). More complete results will be shared at a future scientific conference.

Previously, China’s National Medical Products Administration granted fruquintinib plus sintilimab conditional approval for usage in the treatment of patients with advanced endometrial cancer who have mismatch repair proficient tumors and progression on prior systemic therapy in December 2024.²

FRUSICA-2 is a 2-part trial; the first part is a randomized, open-label, and active-controlled portion evaluating the treatment combination compared with axitinib (Inlyta) or everolimus (Afinitor) in second-line RCC, and the second part will add a fruquintinib monotherapy factorial cohort to evaluate the efficacy and safety of the monotherapy in the patient population.³

“The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced RCC. Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in China,” Dingwei Ye, MD, PhD, professor at Fudan University Shanghai Cancer Center, China, and co-leading principal investigator of the trial, stated in the press release.¹ “Optimizing the selection of targeted therapy, either as monotherapy or in combination with immunotherapy, for individual patients is a key focus of clinical interest. The results from the FRUSICA-2 study underscore the potential of the sintilimab and fruquintinib combination to address the pressing medical needs of patients with this challenging disease.”

As of January 3, 2025, the trial enrolled a total of 265 patients who were randomly assigned, in a 1:1 ratio, to receive fruquintinib plus sintilimab, or axitinib or everolimus monotherapy.³ Patients received 5 mg of oral fruquintinib daily for 2 weeks on and 1 week off plus 200 mg of sintilimab via intravenous infusion every 3 weeks, or 5 mg of oral axitinib twice daily with dose escalation at the investigator’s discretion or 10 mg of oral everolimus daily. In the fruquintinib monotherapy cohort of part 2, patients will receive 5 mg of oral fruquintinib daily for 3 weeks on and 1 week off.

Eligible patients were between 18 and 75 years of age with histologically or cytologically confirmed locally advanced or metastatic RCC who progressed during or after previous first-line VEGFR-TKI therapy. Additionally, patients had at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.

The primary trial end points are PFS by blinded independent central review (BICR) per RECIST v1.1 criteria in part 1 and ORR in part 2. Secondary end points include safety in parts 1 and 2, quality of life in part 1, disease control rate, DOR, time to response, and overall survival.

Additionally, in January 2025, results from a phase 1b/2 trial (NCT03903705) evaluating fruquintinib plus sintilimab in previously treated RCC were published in Targeted Oncology.⁴ At a median follow-up of 45.7 months, the confirmed ORR was 60.0% (95% CI, 36.1%-80.9%), the median PFS was 15.9 months (95% CI, 5.4-19.3), and the median DOR was 13.9 months (95% CI, 9.0-not evaluable).

Professor Zhisong He, from Peking University First Hospital and the co-leading principal investigator of the study, stated in the press release, “The positive results from this phase 3 study of the sintilimab and fruquintinib combination represent a significant advancement in the treatment of advanced RCC. We are optimistic about the clinical implications of the findings as we strive to provide more effective treatment options for patients who may not have had adequate responses to previous therapies.”¹

References

1. Innovent and HUTCHMED jointly announce that the FRUSICA-2 phase 2/3 Study of sintilimab and fruquintinib combination has met its primary endpoint in advanced renal cell carcinoma in China. News release. HUTCHMED Limited. March 18, 2025. Accessed March 19, 2025. https://tinyurl.com/mutv4fvv
2. HUTCHMED and Innovent jointly announce NMPA conditional approval for ELUNATE (fruquintinib) in combination with TYVYT (sintilimab injection) for the treatment of advanced endometrial cancer. News release. HUTCHMED (China) Limited and Innovent Biologics, Inc. December 3, 2024. Accessed March 19, 2025. https://tinyurl.com/2ww7h2de
3. Efficacy and safety of fruquintinib in combination with sintilimab in advanced renal cell carcinoma (FRUSICA-2). ClinicalTrials.gov. Updated January 3, 2025. Accessed March 19, 2025. https://tinyurl.com/d5s5mtjb
4. Xu H, Yao X, He Z, et al. Fruquintinib plus sintilimab in patients with treatment-naive and previously treated advanced renal cell carcinoma: results from a phase Ib/II clinical trial. Target Oncol. 2025;20(1):113-125. doi:10.1007/s11523-024-01120-6