NMPA approves HutchMed and Innovent’s Elunate and Tyvyt combination for renal cell carcinoma

Edited by Robert McTiernan··2 min read

HutchMed (China) Limited (Nasdaq/AIM: HCM; HKEX: 13) and Innovent Biologics (HKEX: 1801) jointly announced that China’s National Medical Products Administration (NMPA) has approved the VEGF inhibitor Elunate (fruquintinib) in combination with PD-1 inhibitor Tyvyt (sintilimab injection) for the second-line treatment of locally advanced or metastatic renal cell carcinoma, marking the tenth approved indication for sintilimab in China and extending fruquintinib’s approved combination profile beyond its existing colorectal cancer and endometrial cancer uses.

The approved indication covers patients who have failed prior VEGFR-tyrosine kinase inhibitor therapy and have not received PD-1 or PD-L1 inhibitor therapy in the first-line setting. The regimen combines fruquintinib, an oral selective inhibitor of VEGFR-1, -2, and -3, with sintilimab, an IgG4 anti-PD-1 monoclonal antibody. Fruquintinib suppresses tumor angiogenesis through sustained VEGFR blockade, while sintilimab restores T-cell-mediated antitumor activity by disrupting the PD-1/PD-L1 checkpoint axis. The combination is designed to target complementary immunosuppressive and pro-angiogenic mechanisms simultaneously.

FRUSICA-2 study results

The approval is supported by data from FRUSICA-2 (NCT05522231), a Phase III randomized, open-label, active-controlled registration study comparing fruquintinib plus sintilimab against axitinib or everolimus monotherapy in patients with locally advanced or metastatic RCC in the second-line setting. The primary endpoint was progression-free survival as assessed by blinded independent central review. As of the February 2025 data cutoff, median PFS was 22.2 months in the combination arm versus 6.9 months in the control arm, corresponding to a stratified hazard ratio of 0.373 and a log-rank p-value of less than 0.0001. The objective response rate was 60.5% versus 24.3%, and median duration of response was 23.7 months versus 11.3 months. Overall survival data remained immature at the cutoff, with approximately 20% maturity. Results were presented at the 2025 ESMO Congress.

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Mechanistic rationale and context

The pairing of a selective VEGFR inhibitor with a PD-1 checkpoint inhibitor reflects a strategy increasingly used in RCC, where tumor vasculature and immune evasion are both established drivers of disease progression. Fruquintinib’s design prioritizes selectivity across VEGFR-1, -2, and -3 with limited off-target kinase activity, a profile the companies have argued supports tolerability in combination settings. Sintilimab’s IgG4 backbone blocks PD-1 interactions with both PD-L1 and PD-L2, restoring cytotoxic T-cell function in the tumor microenvironment.

The approval positions the combination within a second-line RCC landscape that, globally, includes nivolumab (Bristol-Myers Squibb), approved by the US FDA in 2015 based on the CheckMate-025 trial in post-VEGFR-TKI patients, and cabozantinib (Exelixis), approved in 2016 following the METEOR trial. Both agents have established second-line profiles in populations that overlap substantially with the FRUSICA-2 indication. The fruquintinib-sintilimab combination adds a dual-mechanism regimen to this setting, though no head-to-head data against nivolumab or cabozantinib are available, and cross-trial comparisons carry inherent limitations.

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