China’s NMPA Accepts NDA for Sintilimab Plus Fruquintinib in Second-Line Advanced/Metastatic RCC

Sintilimab Plus Fruquintinib in Advanced/Metastatic RCC

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China’s National Medical Products Administration (NMPA) has accepted a new drug application (NDA) seeking the approval of sintilimab (Tyvyt) in combination with fruquintinib (Fruzaqla) for the treatment of patients with locally advanced or metastatic renal cell carcinoma (RCC) who have failed treatment with 1 prior TKI.1

The NDA is supported by data from the phase 2/3 FRUSICA-2 trial (NCT05522231). In March 2025, HUTCHMED and Innovent Biologics jointly announced that the study had met its primary end pointof progression-free survival (PFS) per RECIST 1.1 criteria by blinded independent central review (BICR).2 The combination also demonstrated improvements in key secondary end points of objective response rate (ORR) and duration of response (DOR).1 The safety profile of the combination was tolerable and no new safety signals were reported.

“The second NDA acceptance of sintilimab and fruquintinib combination represents a significant step toward providing a more effective treatment option for patients with second-line advanced RCC in China,” Hui Zhou, PhD, senior vice president of Innovent Biologics, stated in a news release. “Our PD-1 inhibitor, sintilimab has solidified its position as a cornerstone of immuno-oncology [IO] therapy with this NDA as its 10th indication, marking a meaningful milestone in lifecycle management and clinical value optimization.”

FRUSICA-2 was an open-label, active-controlled study that enrolled patients withhistologically or cytologically confirmed locally advanced or metastatic RCC who experienced disease progression during or after, or were intolerant to, a frontline VEGFR TKI regimen.3 Eligible patients needed to be 18 to 75 years old, 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 a daily dose of 5 mg for 2 weeks on and 1 week off plus 200 mg of sintilimab once every 3 weeks during each 3-week cycle or 10 mg of daily everolimus (Afinitor) every 3 weeks. Following the completion of part 1, enrollment to part 2 will be initiated and approximately 15 to 30 patients will receive single-agent fruquintinib.

The primary end point in part 1 was PFS per RECIST 1.1 criteria by BICR assessment; in part 2, the primary end point was investigator-assessed ORR per RECIST 1.1 criteria. Secondary end points included PFS, disease control rate, ORR, DOR, time to response, overall survival, and safety.

In December 2024, the NMPA conditionally approved fruquintinib plus sintilimab in patients with advanced mismatch repair–proficient, advanced endometrial cancer who experience disease progression following systemic therapy and were not candidates for curative surgery or radiation.4 The conditional approval was supported by data from the phase 2 FRUSICA-1 study (NCT03903705). Innovent Biologics noted that data from FRUSICA-2 will be presented during an upcoming scientific conference.1

“Kidney cancer continues to pose significant challenges in China, with limited treatment options for patients who [progress on] first-line therapies,” Michael Shi, PhD, head of Research and Development and chief medical officer of HUTCHMED, added in the news release. “Submitting this NDA for the fruquintinib and sintilimab combination for advanced renal cell carcinoma marks an important step in our efforts to address this unmet need. We are dedicated to making this combination therapy available to patients with renal cell carcinoma. At the same time, through ongoing research, we remain focused on exploring the full potential of this combination, as well as advancing our broader pipeline across multiple cancer types, to provide more patients with new and effective treatment options.”

References

1. Innovent and HUTCHMED jointly announce NDA acceptance in China for sintilimab combination with fruquintinib for the treatment of advanced renal cell carcinoma. News release. Innovent Biologics. June 5, 2025. Accessed June 5, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=537
2. 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 June 5, 2025. https://www.hutch-med.com/frusica2-china-phase-iii-of-fruquintinib-sintilimab-met-primary-endpoint-in-rcc/
3. Efficacy and safety of fruquintinib in combination with sintilimab in advanced renal cell carcinoma (FRUSICA-2). ClinicalTrials.gov. Updated January 3, 2025. Accessed June 5, 2025. https://clinicaltrials.gov/study/NCT05522231
4. 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 Biolog
   ics, Inc. December 3, 2024. Accessed June 5, 2025. https://www.hutch-med.com/fruquintinib-sintilimab-conditional-approval-for-endometrial-cancer/