NMPA Conditionally Approves ELUNATE® and TYVYT® Combo for Advanced Endometrial Cancer, Announce HUTCHMED and Innovent

HUTCHMED (China) Limited and Innovent Biologics, Inc. have announced that their New Drug Application for combining ELUNATE® (fruquintinib) and TYVYT® (sintilimab injection) has been conditionally approved by the National Medical Products Administration (NMPA) of China. This approval is targeted at treating patients with advanced endometrial cancer possessing Mismatch Repair proficient (pMMR) tumors, who have not responded to previous systemic therapy and lack options for curative surgery or radiation. This represents the first regulatory approval for fruquintinib when used in combination with an immune checkpoint inhibitor.

The NMPA's conditional approval was based on data from the FRUSICA-1 study, a registration cohort of a Phase II trial that was multi-center and open-label. The study focused on patients with endometrial cancer who had encountered disease recurrence or progression despite treatment with platinum-based chemotherapy. FRUSICA-1 results, presented at the American Society of Clinical Oncology meeting in June 2024, highlighted an objective response rate of 35.6% and a disease control rate of 88.5%. The combination treatment demonstrated fast-acting efficacy, with a median response time of 1.6 months. The median progression-free survival was 9.5 months, while overall survival was 21.3 months. The adverse effects of the combination therapy were consistent with those of similar treatments.

Professor Xiaohua Wu, who led the FRUSICA-1 study, emphasized that this approval could drastically change the management of advanced endometrial cancer. With the combination's effectiveness and manageable safety profile, it provides a much-needed option for patients who have limited responses to traditional therapies. Dr. Michael Shi of HUTCHMED also noted that the approval underscores the potential of combining fruquintinib with other therapies to enhance patient outcomes. Dr. Hui Zhou from Innovent appreciated the approval as a significant advancement, aiming to improve survival and quality of life for patients with this aggressive form of cancer.

HUTCHMED and Innovent have been jointly developing this combination therapy, which received Breakthrough Therapy Designation from the NMPA in July 2023. This designation was based on the therapy's potential to address severe conditions with no effective treatments and demonstrated significant advantages over existing options. A Phase III confirmatory study is planned to further investigate the combination's effectiveness.

Endometrial cancer, originating in the uterus, is a significant health challenge globally, with around 417,000 new diagnoses and about 97,000 deaths in 2020. In China alone, 82,000 new cases and 17,000 deaths were reported the same year. While early-stage endometrial cancer can often be treated surgically, recurrent or metastatic cases have poor outcomes and limited treatment options.

Fruquintinib is an oral inhibitor of vascular endothelial growth factor receptors, which are crucial in inhibiting tumor angiogenesis. It is designed to have enhanced selectivity to limit off-target effects, making it suitable for combination therapies. Fruquintinib is already approved in China for metastatic colorectal cancer and has been marketed under the brand name ELUNATE®. It has also received approvals in the US, EU, and other regions, with ongoing regulatory submissions worldwide.

Sintilimab, marketed as TYVYT® in China, is a PD-1 monoclonal antibody co-developed with Eli Lilly. It reactivates T-cells to kill cancer cells by blocking the PD-1/PD-Ligand 1 pathway. Sintilimab has been approved in China for various indications, including several types of lung cancer and hepatocellular carcinoma.

This new combination therapy approval for advanced endometrial cancer adds to the list of indications for sintilimab and marks a meaningful step forward in treatment options available for this challenging cancer.