Innovent Biologics and HUTCHMED jointly announced that the China National Medical Products Administration (NMPA) has granted conditional approval for the combination of TYVYT® (sintilimab injection) and ELUNATE® (fruquintinib) for the treatment of patients with advanced endometrial cancer. This approval is specifically for patients with Mismatch Repair proficient (pMMR) tumors who have failed prior systemic therapy and are not candidates for curative surgery or radiation.
The conditional approval is based on data from the FRUSICA-1 study, a multi-center, open-label Phase 2 trial. The study investigated sintilimab in combination with fruquintinib in endometrial cancer patients who experienced disease recurrence, progression, or intolerable toxicity after platinum-based doublet chemotherapy. The results, presented at the American Society of Clinical Oncology (ASCO) annual meeting in June 2024, showed promising efficacy and a manageable safety profile.
Clinical Trial Results
The FRUSICA-1 study demonstrated an IRC-assessed objective response rate (ORR) of 35.6% and a disease control rate (DCR) of 88.5%. The combination treatment exhibited a rapid onset of efficacy, with a median time to tumor response (mTTR) of only 1.6 months. The median progression-free survival (PFS) reached 9.5 months, and the median overall survival (OS) was 21.3 months. The adverse events observed were consistent with those reported for similar immunotherapy and anti-angiogenic agent combinations.
Prof. Xiaohua Wu, Director of the Department of Gynecologic Oncology at Fudan University Affiliated Cancer Hospital and Principal Investigator of the FRUSICA-1 study, stated, "This approval of sintilimab plus fruquintinib could represent a paradigm shift in managing this challenging disease... With the promising efficacy and manageable safety profile observed in clinical trials, we are eager to have this treatment option available to patients."
Addressing Unmet Needs in Endometrial Cancer
Endometrial cancer, originating in the uterus, remains a significant global health challenge. In 2020, approximately 417,000 people worldwide were diagnosed with endometrial cancer, resulting in around 97,000 deaths. In China alone, an estimated 82,000 new cases and 17,000 deaths were reported that year. While early-stage cases can often be surgically resected, recurrent and/or metastatic endometrial cancer presents a high unmet need due to poor outcomes and limited treatment options.
About Sintilimab and Fruquintinib
Sintilimab, marketed as TYVYT®, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. It functions by binding to PD-1 molecules on T-cells, blocking the PD-1/PD-L1 pathway, and reactivating T-cells to kill cancer cells. Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR-1, -2, and -3), playing a pivotal role in inhibiting tumor angiogenesis.
Future Directions
A Phase 3 confirmatory study of the sintilimab and fruquintinib combination in this setting has been planned (NCT06584032). This study aims to further validate the efficacy and safety of the combination therapy in a larger patient population.
Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, commented, "This NMPA approval of fruquintinib in combination with sintilimab represents a significant advancement for patients with advanced endometrial cancer who have long awaited more effective treatments."
