Fruquintinib plus sintilimab in treated advanced endometrial cancer (EMC) patients (pts) with PMMR status: Results from a multicenter, single-arm phase 2 study.

5619 Background: Antiangiogenic therapy plus immunotherapy significantly improved PFS and OS as compared to chemotherapy among pts with previously treated advanced EMC per KEYNOTE-775 study. However, no combination immunotherapies are currently approved for EMC in China. Fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) showed encouraging antitumor activity in multiple solid tumors. Here, we reported the results of F plus S in treated EMC with pMMR status from an open-label, single-arm registrational phase 2 study (NCT03903705). Methods: Eligible pts had histologically confirmed, previously treated advanced EMC with pMMR status confirmed by central lab. They received F (5 mg QD, 2 weeks on/1 week off, orally) plus S (200 mg, IV, Q3W) in 21-day cycles until disease progression or unacceptable toxicity. The primary endpoint was IRC-assessed ORR per RECIST v1.1. Secondary endpoints included DCR, DoR PFS, and OS. Results: As of data cutoff date (November 15, 2023), a total of 98 pts with pMMR status were enrolled and received the combination treatment. All pts had previously received at least first-line platinum-containing systemic therapy, and 22.4% pts had received bevacizumab therapy. Detailed disease histories are summarized in the table. With the median (95% CI) follow-up time of 15.7m (14.6, 17.7), 87/98 pts had at least one post-baseline tumor assessment result (efficacy evaluable pts), among them, IRC-assessed ORR and DCR was 35.6% (CR: 2/87 and PR: 29/87) and 88.5% respectively; DoR was not reached and the 9m-DoR rate was 80.7%. Among 98 pts, the median (95% CI) PFS and OS was 9.5m (5.6, -) and 21.3m (17.3, -) respectively. Based on prior bevacizumab therapy (Yes vs No), ORR was 40.9% vs 30.3%, and median (95%CI) PFS was 13.8m (4.1, -) vs 9.5m (5.5, -). All pts experienced TEAEs, and the most common ≥Grade 3 TEAEs included hypertension (18.4%), hypertriglyceridaemia (11.2%), and palmar-plantar erythrodysaesthesia syndrome (11.2%). Conclusions: F plus S showed meaningful efficacy improvements in advanced EMC pts with pMMR status, regardless of prior bevacizumab treatment. The combination therapy had a manageable toxicity profile. F plus S could offer a new potential treatment option for this patient population. Clinical trial information: NCT03903705 . [Table: see text]