A phase II trial of lenvatinib plus pembrolizumab in patients (pts) with endometrial or ovarian carcinosarcoma.

5615 Background: Carcinosarcoma is a rare and aggressive histology of gynecologic carcinomas that has limited treatment options and is often excluded from larger therapeutic clinical trials. In KN775, treatment with multikinase inhibitor lenvatinib plus PD-1 inhibitor pembrolizumab led to significantly longer progression-free survival (PFS) and overall survival (OS) than chemotherapy among patients with previously treated advanced non-carcinosarcoma endometrial carcinomas. We report results from a phase 2 trial of lenvatinib + pembrolizumab in pts with endometrial or ovarian carcinosarcoma. Methods: In this open label, single institution, investigator initiated, phase 2 study, pts had confirmed recurrent/persistent endometrial or ovarian carcinosarcoma with progression after at least 1 prior platinum chemotherapy but no more than 3 prior lines, measurable disease, and ECOG performance status ≤1. Pts received oral lenvatinib 20 mg/day plus pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoints were objective response rate (ORR) per RECIST v1.1 and PFS rate at 27 weeks (PFR27). Secondary endpoints included median duration of response (mDOR), clinical-benefit rate (CBR: complete response (CR) + partial response (PR) + stable disease (SD) at 27 weeks), median overall survival (mOS), and safety. Next generation sequencing, MSK-IMPACT, was performed on tumors from all 27 patients for exploratory analysis. Results: As of data cutoff on 12/15/2025, 27 pts enrolled; median age was 63 years (range: 51−79); and at least 26.4% pts were non-white. Primary tumor site was 63% (17/27) endometrial and 37% (10/27) ovarian; tumors were 19% (5/27) dMMR and 81% (22/27) pMMR. Confirmed ORR was 18.5% (5/27; 0 CRs, 3 PRs in endometrial, 2 PRs in ovarian), meeting the interim analysis primary endpoint. Of the 5 confirmed responses, 4 occurred in pts with pMMR tumors, and 1 in a pt with dMMR tumor. There are 2 additional unconfirmed PRs. Responses in pts with ovarian tumors included 1 platinum-sensitive and 1 platinum-resistant. PFR27 was 35.7% (90% CI: 24 - 100), mDOR was 26.5 months (80% CI: 3.8 - NE), CBR was 37% (80% CI: 24.4 - 51.2), and mOS was 15.3 months (95% CI: 7.1 – 24.4). Two pts remain on treatment and were censored for time to event analyses. All pts had at least one treatment-emergent adverse event (TEAE). The most common TEAEs were fatigue (74%), hypertension (56%), diarrhea (52%), anorexia (48%), and weight loss (48%). Grade 3 and 4 TEAEs occurred in 44% and 7.4% patients, respectively. There were no grade 5 TEAEs. 5 Pts (19%) discontinued study treatment due to TEAEs. Further genomic analyses are underway. Conclusions: Encouraging efficacy and durable responses were observed in endometrial and ovarian carcinosarcoma pts treated with lenvatinib + pembrolizumab, regardless of MMR status or primary site. The study met its predefined interim analysis endpoint. No new safety signals were identified. Clinical trial information: NCT02501096 .