Cadonilimab Combined With RT in LACC Patients Ineligible for CCRT

Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). However, a substantial proportion of patients have contraindications to cisplatin based chemotherapy due to advanced age, renal impairment, cardiac dysfunction, or other comorbidities. For these patients, no evidence based standardised treatment exists. Immunotherapy combined with radiotherapy may offer a chemotherapy sparing alternative. Cadonilimab, a PD 1/CTLA 4 bispecific antibody, has demonstrated significant efficacy in advanced cervical cancer. This study aims to evaluate the efficacy and safety of cadonilimab combined with radical radiotherapy in LACC patients ineligible for concurrent chemotherapy.

This is an investigator initiated, prospective, single centre, single arm, open label, Simon's two stage phase II trial. A total of 45 patients will be enrolled. Eligible participants are women aged \>18 years with histologically confirmed cervical squamous cell carcinoma or adenosquamous carcinoma, FIGO 2018 stage IB3-IVA, and absolute or relative contraindications to cisplatin based chemotherapy. All patients will receive radical radiotherapy (external beam radiotherapy 45-50.4 Gy/25-28 fractions plus high dose rate brachytherapy 6-8 Gy × 3-5 fractions) concurrently with three cycles of cadonilimab 10 mg/kg intravenously every 3 weeks. The primary endpoint is complete response (CR) rate assessed at 4 weeks post radiotherapy. Secondary endpoints include 2 year progression free survival, 2 year local control, 2 year locoregional control, 5 year overall survival, safety (CTCAE v5.0 and RTOG late toxicity), and quality of life (EORTC QLQ C30 and QLQ BR23). Assuming a historical CR rate of 69% with radiotherapy alone, we hypothesise that the combination will increase CR to 85%. With α=0.05 (two sided) and 80% power, Simon's optimal two stage design requires 43 evaluable patients; after accounting for 5% dropout, 45 patients will be recruited.