Sintilimab plus fruquintinib under review in China for advanced renal cell carcinoma

China’s National Medical Products Administration (NMPA) has accepted a new drug application (NDA) seeking approval of sintilimab (Tyvyt) plus fruquintinib (Elunate) for patients with locally advanced or metastatic renal cell carcinoma (RCC) who have failed prior treatment with 1 tyrosine kinase inhibitor (TKI), Innovent and HUTCHMED announced in a joint news release.¹

The safety profile for sintilimab plus fruquintinib was also manageable.

"Kidney cancer continues to pose significant challenges in China, with limited treatment options for patients who fail first-line therapies,” said Michael Shi, PhD, head of R&D and chief medical officer of HUTCHMED, in the news release.¹ 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."

The NDA is backed by data from the phase 2/3 FRUSICA-2 trial (NCT05522231), which met its primary end point by demonstrating that the combination of sintilimab plus fruquintinib extended progression-free survival (PFS) vs axitinib (Inlyta) or everolimus (Afinitor) monotherapy in the second-line setting. The combination also showed improvements in the study’s secondary end points of objective response rate (ORR) and duration of response (DOR).

The safety profile for sintilimab plus fruquintinib was also manageable. No new safety signals were reported.

According to Innovent and HUTCHMED, data from the trial are set to be presented at an upcoming medical meeting.

China’s NMPA also granted a conditional approval to the combination of sintilimab and fruquintinib in December 2024 for the treatment of patients with advanced mismatch repair proficient endometrial cancer who have failed prior systemic therapy and are not candidates for curative surgery or radiation.

“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 renal cell carcinoma in China,” said Hui Zhou, PhD, Senior Vice President of Innovent, in the news release.¹ “Our PD-1 inhibitor, sintilimab (TYVYT), 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.”

In total, the open-label FRUSICA-2 trial planned to enroll 265 adult patients across 48 clinical trial sites in China.² To be eligible for enrollment, patients needed to have at least 1 measurable lesion per RECIST v1.1, an ECOG performance score of 0 or 1, and adequate organ function. All patients had progressed or were intolerant to previous first-line VEGFR-TKI therapy and received the study drug(s) in the second-line setting.

Those included in the study were randomly assigned 1:1 to receive 200 mg sintilimab every 3 weeks plus 5 mg fruquintinib once per day by mouth or to monotherapy with either 5 mg axitinib twice per day or 10 mg everolimus once per day by mouth. Part 2 of the study also included a fruquintinib monotherapy arm, which planned to enroll approximately 15 to 30 patients.

The primary end points for the study included PFS per RECIST v1.1 by blinded independent central review and ORR. The investigators also assessed the disease control rate, DOR, and overall survival, in addition to safety and quality of life measures.

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. Published online and accessed June 5, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=537

2. Efficacy and safety of fruquintinib in combination with sintilimab in advanced renal cell carcinoma (FRUSICA-2). ClinicalTrials.gov. Last updated January 3, 2025. Accessed March 19, 2025. https://clinicaltrials.gov/study/NCT05522231