Analysis of serous carcinoma subgroup in FRUSICA-1: Fruquintinib plus sintilimab in treated advanced endometrial cancer (EMC) patients (pts) with pMMR status.

5596 Background: Serous carcinoma represents approximately 10% of all EMC, has the highest recurrence rate and is responsible for a disproportionate 40% of mortality in EMC. Additionally, the overall 5-year survival rate is only 33% for stage III-IV serous carcinoma. Fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) was evaluated in an open-label, single-arm phase 2 pivotal study (FRUSICA-1, NCT03903705), and demonstrated encouraging efficacy and favorable safety profile in treated advanced EMC pts with pMMR (proficient mismatch repair) status (Wu X, et al; 2024 ASCO). Here, we report the ad hoc updated analysis results of the serous carcinoma subgroup (data cutoff: May 15, 2024). 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. Ad hoc analyses were conducted to evaluate the primary endpoint (ORR) and secondary endpoints (DCR, DoR, TTR, PFS, OS, and safety) of F+S in pts with endometrial serous carcinoma. Results: As of data cutoff date (May 15, 2024), 98 EMC pts with pMMR status were enrolled and received the combination treatment (ITT population), among them, 27 pts had serous carcinoma. In these 27 pts, median age was 63.1 years, 22 (81.5%) pts were in stage Ⅳ disease, 7 (25.9%) pts had received prior bevacizumab therapy, and 5 (18.5%) pts had received prior pelvic radiotherapy. IRC-assessed ORR was 37.0% (95%CI: 19.4%, 57.6%), DCR was 88.9% (95%CI: 70.8%, 97.7%). Median DoR and TTR was 17.9 (95%CI: 3.3, not estimable [NE]) months, and 2.4 (95%CI: 1.2, 4.0) months, respectively. With the median PFS and OS follow-up of 8.3 and 21.7 months, the median PFS and OS was 8.8 (95%CI: 6.9, 19.2) months and 19.0 (95%CI: 11.4, NE) months, respectively. These efficacy findings were similar with those observed in ITT population. Grade ≥3 treatment related adverse events (TRAE) occurred in 63.0% pts, and the most common ≥Grade 3 TRAEs included palmar-plantar erythrodysesthesia syndrome (22.2%) and hypertension (11.1%). Conclusions: F+S was tolerable and showed clinically meaningful efficacy in endometrial serous carcinoma, characterized by durable responses that were comparable across the ITT population. Clinical trial information: NCT03903705 .