HUTCHMED and Innovent Biologics announced today that their FRUSICA-2 Phase II/III clinical trial has met its primary endpoint, demonstrating significant efficacy for the combination of fruquintinib and sintilimab in the second-line treatment of locally advanced or metastatic renal cell carcinoma (RCC).
The study evaluated the fruquintinib-sintilimab combination against axitinib or everolimus monotherapy, with results showing superior progression-free survival (PFS) per RECIST 1.1 criteria as assessed by blinded independent central review. The combination also showed improvements in key secondary endpoints including objective response rate (ORR) and duration of response (DoR).
Addressing Unmet Needs in RCC Treatment
Renal cell carcinoma represents approximately 90% of kidney cancers, with an estimated 435,000 new patients diagnosed worldwide in 2022. In China alone, approximately 74,000 new kidney cancer cases were diagnosed that year.
Prof. Dingwei Ye of Fudan University Shanghai Cancer Center, co-leading Principal Investigator of the FRUSICA-2 study, emphasized the significance of the findings: "The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced renal cell carcinoma. Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in China."
While several immune-oncology combination therapies have been approved for first-line treatment of advanced RCC in the United States, treatment options remain limited in China, particularly for patients who have failed prior targeted therapy.
Promising Clinical Data
The FRUSICA-2 results build upon earlier promising data from a Phase Ib/II study of the fruquintinib-sintilimab combination. In that earlier study, with data cutoff in October 2024, the combination demonstrated a confirmed ORR of 60.0% and disease control rate of 85.0% among 20 previously treated patients. The median duration of response was 13.9 months, and median PFS was 15.9 months, with overall survival not yet reached at 36 months.
"The positive results from this Phase III study of the fruquintinib and sintilimab combination represent a significant advancement in the treatment of advanced renal cell carcinoma," said Prof. Zhisong He of Peking University First Hospital, co-leading Principal Investigator. "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."
Mechanism of Action
The combination pairs two distinct mechanisms of action. Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), designed with enhanced selectivity to limit off-target kinase activity. This allows for sustained target inhibition while maintaining flexibility for combination therapy.
Sintilimab is a PD-1 immunoglobulin G4 monoclonal antibody that binds to PD-1 molecules on T-cells, blocking the PD-1/PD-L1 pathway and reactivating T-cells to attack cancer cells.
Regulatory Status and Future Plans
The fruquintinib-sintilimab combination has already received conditional approval from China's National Medical Products Administration (NMPA) for treating patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.
Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, expressed gratitude to the study participants: "The encouraging results from our study provide clear evidence for the combination of fruquintinib and sintilimab as a viable new treatment option for advanced renal cell carcinoma patients who have progressed on previous therapy. We look forward to sharing detailed findings with regulatory authorities and progressing toward NDA filings in the coming months."
Dr. Hui Zhou, Senior Vice President of Innovent, added, "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."
Full results from the FRUSICA-2 trial will be submitted for presentation at an upcoming scientific conference, with regulatory submissions expected to follow.
Broader Development Program
Fruquintinib is already approved for the treatment of metastatic colorectal cancer in multiple regions, including China (marketed as ELUNATE®), the United States, European Union, United Kingdom, Japan, and several other countries (marketed as FRUZAQLA®). The drug was designed to have enhanced selectivity to limit off-target effects while achieving sustained inhibition of tumor angiogenesis.
Sintilimab, marketed as TYVYT® in China, has been approved for seven indications in China and is included in the National Reimbursement Drug List. The combination of fruquintinib and sintilimab represents a promising approach for addressing the significant unmet needs in advanced RCC treatment, particularly for patients who have progressed on previous therapies.
