Fruquintinib/Sintilimab Generates Favorable PFS Outcomes in Advanced RCC

The phase 2/3 FRUSICA-2 trial (NCT05522231) met its primary end point of improved progression-free survival (PFS) per RECIST 1.1 criteria per blinded independent central review assessment with fruquintinib (Fruzaqla) plus sintilimab (Tyvyt) vs monotherapy comparator agents in the second-line setting in patients with locally advanced or metastatic renal cell carcinoma (RCC) in China.1

The combination also generated improvements in overall response rate (ORR) and duration of response (DOR), according to a news release from HUTCHMED Limited and Innovent Biologics, Inc. Full results from the trial will be submitted for presentation at an upcoming meeting.

“The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced RCC,” Dingwei Ye, MD, PhD, of Fudan University Shanghai Cancer Center in China and co-leading principal investigator (PI) of FRUSICA-2, stated in the news release. “Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in China. 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 fruquintinib and sintilimab combination to address the pressing medical needs of patients with this challenging disease.”

The FRUSICA-2 trial consists of 2 parts.2 Part 1 is a randomized, open-label, active-controlled study evaluating the efficacy and safety of second-line fruquintinib plus sintilimab vs axitinib (Inlyta) or everolimus (Afinitor) monotherapy in patients with locally advanced or metastatic RCC. Part 2, which was planned to begin enrollment after enrollment to part 1 was complete, is a fruquintinib monotherapy factorial cohort study that will investigate the efficacy and safety of second-line fruquintinib monotherapy in this patient population.

To enroll in the study, patients needed at least 18 years old and no more than 75 years of age; have histologically or cytologically confirmed locally advanced or metastatic RCC; have disease progression during or after or intolerance to prior frontline VEGFR-TKI therapy for advanced or metastatic disease; have at least 1 measurable lesion per RECIST 1.1 criteria; have an ECOG performance status of 0 or 1; and have adequate organ function.

In part 1, patients were randomly assigned 1:1 to receive fruquintinib at 5 mg once daily for 2 weeks on and 1 week off in combination with sintilimab at 200 mg once every 3 weeks during each 3-week cycle; or control treatment with either axitinib at 5 mg twice daily or everolimus at 10 mg once daily every 3 weeks.

Key secondary end points of part 1 included PFS per RECIST 1.1 criteria, safety, quality of life, disease control rate, ORR, DOR, time to response, and overall survival.

“The positive results from this phase 3 study of the fruquintinib and sintilimab combination represent a significant advancement in the treatment of advanced RCC,” Zhisong He, MD, PhD, of Peking University First Hospital in China and co-leading PI of FRUSICA-2, added in the news release.1 “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.”

In the news release, HUTCHMED and Innovent leadership noted that findings from FRUSICA-2 will be shared with regulatory authorities and that new drug applications seeking the approval of fruquintinib plus sintilimab for patients with RCC will be filed in the coming months.

In December 2024, China’s NMPA granted conditional approval to fruquintinib plus sintilimab injection for the treatment of patients with advanced mismatch repair–proficient, advanced endometrial cancer who have progressed on prior systemic therapy and are not candidates for curative surgery or radiation.3 This regulatory decision was supported by findings from the endometrial cancer registration cohort of the phase 2 FRUSICA-1 trial (NCT03903705).

Notably, in 2023, the FDA approved fruquintinib for the treatment of adult patients with metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and—if RAS wild-type and medically appropriate—an anti-EGFR therapy.4 The approval was supported by data from the phase 3 FRESCO-2 (NCT04322539) and FRESCO (NCT02314819) studies.

References

1. HUTCHMED and Innovent jointly announce that the FRUSICA-2 phase II/III study of fruquintinib and sintilimab combination has met its primary endpoint in advanced renal cell carcinoma in China. News release. HUTCHMED Limited. March 19, 2025. Accessed March 19, 2025. https://www.hutch-med.com/frusica2-china-phase-iii-of-fruquintinib-sintilimab-met-primary-endpoint-in-rcc/
2. 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://clinicaltrials.gov/study/NCT05522231
3. 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://www.hutch-med.com/fruquintinib-sintilimab-conditional-approval-for-endometrial-cancer/
4. Takeda receives U.S. FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed March 19, 2025. https://www.takeda.com/newsroom/newsreleases/2023/takeda-receives-us-fda-approval-of-fruzaqla-fruquintinib-for-previously-treated-metastatic-colorectal-cancer/