Sintilimab/fruquintinib combo meets primary PFS end point in advanced RCC

The primary end point of progression-free survival (PFS) has been met in the phase 2/3 FRUSICA-2 trial (NCT05522231), evaluating sintilimab injection (Tyvyt) plus fruquintinib (Elunate) for the treatment of patients with locally advanced or metastatic renal cell carcinoma (RCC) in China.¹

The companies plan to initiate submission of an NDA in the coming months.

According to a joint news release from Innovent Biologics and HUTCHMED, the combination demonstrated an improved 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).

Full results from the FRUSICA-2 trial are being submitted for presentation at an upcoming medical meeting, the companies stated.

"The positive results from this phase 3 study of the sintilimab and fruquintinib combination represent a significant advancement in the treatment of advanced renal cell carcinoma,” said co-principal investigator Prof Zhisong He of Peking University First Hospital, 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 total, the FRUSICA-2 trial planned to enroll 265 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 5 mg axitinib twice per day or 10 mg everolimus once per day by mouth monotherapy. The primary end points 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.

Previous data on the combination

The update on the FRUSICA-2 trial comes shortly after the publication of results from the phase 1b/2 proof-of-concept study (NCT03903705) of the combination earlier this year.³ Overall, data showed encouraging efficacy of sintilimab plus fruquintinib in patients with advanced RCC. The confirmed ORR was 68.2% (95% CI, 45.1-86.1), and the 18-month PFS rate was 59.4%. At the time of data report, the median PFS had not been reached. The combination was also shown to be well-tolerated.

The FRUSICA-2 announcement also follows positive results from the phase 1 FRUSICA-1 trial (NCT03903705), which evaluated the combination of sintilimab plus fruquintinib in patients with advanced solid tumors. Based on the results from that study, China's National Medical Products Administration (NMPA) granted a conditional approval to sintilimab plus fruquintinib for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.⁴

According to Michael Shi, PhD, head of R&D and chief medical officer of HUTCHMED, the team plans to initiate the filing of a new drug application with regulatory authorities in the coming months for potential approval in the advanced RCC indication.

Hui Zhou, PhD, senior vice president of Innovent Biologics, concluded in the news release, "We are encouraged by the positive results in the FRUSICA-2 clinical trial. These outcomes not only underscore the great potential of the combination therapy of sintilimab and fruquintinib but also bring new hope to previously treated patients with advanced renal cell carcinoma. We look forward to working closely with HUTCHMED to jointly advance the registrational communication of this innovative combo therapy and make it available to patients as soon as possible."

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. March 18, 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. Last 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. December 3, 2024. Accessed March 19, 2024. https://www.hutch-med.com/fruquintinib-sintilimab-conditional-approval-for-endometrial-cancer/