Efficacy and safety of cadonilimab combined with chemotherapy as the first-line treatment for primary advanced or recurrent endometrial cancer: a prospective single-arm open-label phase II clinical trial.

Introduction: Recently, immunotherapy has significantly transformed the treatment landscape of endometrial cancer (EC). Results from KEYNOTE-158, RUBY and AtTEnd showed programmed cell death 1 (PD-1) or programmed cell death-ligand 1 inhibitors with promising efficacy in primary advanced or recurrent EC. However, few studies focused on the role of dual immune checkpoints in primary advanced or recurrent EC. Cadonilimab is an immune checkpoint inhibitor targeting the PD-1 and T-lymphocyte antigen-4, which is expected to show substantial clinical efficacy in EC. Combining cadonilimab with standard chemotherapy may have synergistic effects, making this combination a promising first-line treatment for primary advanced or recurrent EC. Furthermore, incorporating molecular classification for guidance on the use of cadonilimab may hold valuable clinical benefits.

Methods and analysis: In this multicentre, open-label, phase II study, patients with histologically confirmed EC were eligible. Forty-five patients will be recruited. Seventeen patients will be enrolled in stage I, and at least seven cases of complete response (CR) and partial response (PR) should be observed before entering stage II. All patients will receive cadonilimab at a dosage of 10 mg/kg along with carboplatin (area under the curve (AUC)=4-5) plus paclitaxel (175 mg/m²) every 3 weeks (Q3W) for 6-8 cycles. Subsequently, patients with CR, PR or stable disease will receive maintenance of cadonilimab at 10 mg/kg Q3W for 24 months or until progressive disease or adverse events are reported. The objective response rate is the primary endpoint. The secondary endpoints include the disease control rate, duration of response, progression-free survival, overall survival and safety. Additionally, exploratory endpoints involve biomarkers that may predict the efficacy of cadonilimab and chemotherapy, as well as their relationship with molecular classifications. The interim analysis will be conducted after 17 patients have been enrolled.

Ethics and dissemination: The study protocol meets the approval of the ethical committee of Fujian Cancer Hospital (K2023-173-04) and all other participating hospitals. Study findings will be disseminated in peer-reviewed publications.

Trial registration number: NCT06066216.