Cadonilimab plus chemotherapie als eerstelijnsbehandeling bij primair gevorderd of recidief endometriumcarcinoom — fase 2

OBJECTIVE: To assess the interim efficacy and safety of cadonilimab, a PD-1/CTLA-4 bispecific antibody, in combination with platinum-based chemotherapy as first-line treatment for patients with primary advanced or recurrent endometrial cancer (EC), with exploratory analyses by molecular subgroups. METHODS: This investigator-initiated, multicenter, open-label, single-arm phase II trial enrolled women aged 18-75 years with histologically confirmed FIGO stage III/IV or recurrent EC. Patients received cadonilimab (10 mg/kg intravenously every 3 weeks) combined with platinum-based chemotherapy, followed by cadonilimab maintenance. The primary endpoint was objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses were performed according to PD-L1 expression, mismatch repair (MMR) status, and molecular subtype. This interim analysis was conducted after 27 efficacy-evaluable patients reached the predefined PFS milestone. RESULTS: Among 27 patients, ORR was 74.1% (95% CI, 55.6%-87.3%), including one complete response (3.7%) and 19 partial responses (70.4%), with a DCR of 96.3%. Median time to response was 2.8 months, and median DoR was 17.8 months (95% CI, 8.8-not estimable). Median PFS was 10.5 months (95% CI, 8.2-not estimable), with a 12-month PFS rate of 49.6%. Median OS was not reached; the 12-month OS rate was 90.2%. ORR was generally consistent across subgroups, while patients with dMMR tumors showed a lower risk of disease progression compared with those with pMMR tumors. Treatment-related adverse events occurred in 77.8% of patients, predominantly grade 1-2; grade ≥ 3 events occurred in 18.5%, with no treatment-related deaths. CONCLUSIONS: Cadonilimab combined with chemotherapy demonstrated clinically meaningful activity and manageable safety as first-line treatment for advanced or recurrent EC, supporting further investigation, particularly in molecularly defined populations.