China’s NMPA Grants Priority Review to Sintilimab Plus Fruquintinib in pMMR/Non–MSI-H Advanced Endometrial Cancer

China’s National Medical Products Administration (NMPA) has accepted and granted priority review to the new drug application (NDA) seeking the approval of sintilimab (Tyvyt) in combination with fruquintinib (Fruzaqla) for the first-line treatment of patients with advanced mismatch repair–proficient (pMMR)/non–microsatellite instability–high (MSI-H) endometrial cancer who experienced disease progression on previous systemic therapy and are not candidates for curative surgery or radiation.¹

The NDA is supported by findings from the endometrial cancer registration cohort of the phase 1b/2 FRUSICA-1 study (NCT03903705), which examined sintilimab plus fruquintinib in patients with endometrial cancer who experienced disease recurrence, progression, or intolerable toxicity following treatment with platinum-based doublet chemotherapy. The primary end point was objective response rate by independent review committee; secondary end points included disease control rate, duration of response, progression-free survival, overall survival, pharmacokinetics, and safety. Data from the study will be submitted for presentation at an upcoming medical meeting.

“Sintilimab injection, as a backbone therapy in immuno-oncology, in combination with an anti-angiogenetic drug, may improve the prognosis for [patients with] endometrial cancer in China,” Hui Zhou, PhD, senior vice president of Innovent, said in a press release. “We are excited about the NDA acceptance and priority review designation, which increases our potential to bring a new treatment option to [patients with] endometrial cancer, and concurrently strengthens the leadership position of sintilimab injection in China."

FRUSICA-1 is an ongoing, open-label, multicenter trial evaluating the safety and preliminary efficacy of fruquintinib monotherapy or in combination with sintilimab in patients with advanced solid tumors. The study planned to enroll approximately 26 to 39 patients to receive the combination in the dose-escalation phase and approximately 314 in the dose-expansion phase, including approximately 129 patients with endometrial cancer.²

In order to be eligible for the endometrial cancer cohort of the combination arm, patients needed to be 18 to 75 years of age with a body mass index of at least 18.5 kg/m²; to have a life expectancy of at least 12 weeks; to have received a maximum of 2 lines of prior platinum-based double drug systemic antitumor therapy; and to have progressive disease, a serious adverse effect, or disease recurrence or progression after a minimum of 4 cycles of platinum-based double drug chemotherapy. Patients who received radical radiotherapy within 4 weeks of the first dose of study treatment, brachytherapy within 60 days before the first dose, and those who previously received an anti–PD-1, -PD-L1, or -CTLA-4 antibody, or prior fruquintinib, were excluded.

In the combination arm, patients received intravenous sintilimab at 200 mg every 3 weeks in combination with either oral fruquintinib at 3 mg daily for 3 weeks on, 1 week off; fruquintinib at 4 mg daily for 3 weeks on, 1 week off; fruquintinib at 5 mg daily for 2 weeks on, 1 week off; or continuous fruquintinib at 3 mg daily. Treatment in all cohorts will continue until disease progression, death, unacceptable toxicity, loss of follow-up, withdrawal of consent, or other conditions which meet the end of treatment criteria.

Previously, in July 2023, the NMPA granted breakthrough therapy designation to sintilimab plus fruquintinib for the treatment of patients with advanced pMMR/non–MSI-H endometrial cancer who experienced disease progression of previous systemic therapy and are not candidates for curative surgery or radiation. This designation was given because the combination potentially represented a new treatment for a serious conidiation for which there are currently no effective therapeutic options and where clinical evidence demonstrates substantial advantages over existing therapies.¹

“This is the first regulatory filing for the combination of fruquintinib and the immune checkpoint inhibitor sintilimab,” Michael Shi, PhD, head of R & D and chief medical officer at HUTCHMED, said in the press release. “It also represents an important step closer to reshaping the treatment landscape for this challenging disease in China. Endometrial cancer remains one of the most common gynecological malignancies. We look forward to bringing this much-awaited treatment advancement to [patients with] endometrial cancer to improve their treatment outcome."

References

1. Innovent and HUTCHMED jointly announce NDA acceptance in China for sintilimab combination with fruquintinib for the treatment of advanced endometrial cancer with priority review status. News release. Innovent Biologics, Inc. April 2, 2024. Accessed April 2, 2024. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=441
2. A phase Ib/​II study to evaluate fruquintinib monotherapy or plus sintilimab in advanced solid tumors. ClinicalTrials.gov. Updated March 28, 2024. Accessed April 2, 2024. https://www.clinicaltrials.gov/study/NCT03903705