Multicenter phase 2 trial of cadonilimab plus lenvatinib for advanced endometrial cancer

Women with advanced endometrial cancer progressing after platinum-based chemotherapy have limited treatment options. The multicenter phase 2 CLEAR-EC trial evaluated the combination of the bispecific antibody cadonilimab (targeting PD-1 and CTLA-4) and the TKI lenvatinib as second-line or later therapy for these women. Three patients were enrolled in the safety run-in, followed by 29 additional patients after the recommended phase 2 dose (RP2D) was established. The primary endpoint was objective response rate (ORR). No dose-limiting toxicities occurred, establishing lenvatinib 16 mg once daily plus cadonilimab 10 mg/kg every three weeks as the RP2D. The trial met its prespecified primary endpoint, with an ORR or 40.6% (95% CI 23.7-59.4). Disease control rate was 81.3% (95% CI 63.6-92.8), median progression-free survival was 13.8 months, and median overall survival was not reached. Grade ≥3 treatment-related adverse events occurred in 40.6% of patients. The authors conclude that the combination of cadonilimab and lenvatinib demonstrated antitumor activity as second- or later-line therapy for advanced endometrial cancer.