Induction cadonilimab combined with chemotherapy followed by chemoradiotherapy for locally advanced cervical cancer: A multicenter, single-arm, phase II trial.

5530 Background: Short-course weekly induction chemotherapy followed by chemoradiotherapy (CCRT) improves survival for locally advanced cervical cancer (LACC) in the CxII and INTERLACE trial. However, only 70% patients achieved objective response (CR or PR) whereas 20% grade 3-4 adverse events were reported during induction chemotherapy in the CxII study. Cadonilimab is a bi-specific antibody targeting both PD-1 and CTLA-4. The COMPASSION-16 trial has recently demonstrated the encouraging effectiveness and safety of cadonilimab combined with chemotherapy in recurrent/metastatic cervical cancer. This study was aimed to assess the combination of induction cadonilimab and chemotherapy before CCRT. Methods: In this multicenter, single-arm, phase 2 study, we used a Simon two-stage design. Previous studies of induction chemotherapy showed a ORR of 68.8%-80% in LACC. Null hypothesis of ORR 80% was adopted in this study. Estimating a ORR of 95% would be achieved following induction therapy, a total of 29 patients (including 9 in the first stage) were required with type I and type II errors set at 0.05 and 0.2, respectively. Eligible patients were women aged 18 years or older, newly diagnosed disease with stage IB3-IVA (International Federation of Gynecology and Obstetrics [FIGO] 2018), with histologically confirmed cervical carcinoma, and had an ECOG performance status of 0 or 1. Patients received 2 cycles of induction therapy consisting of cadonilimab at a dose of 10mg/kg plus nab-paclitaxel at a dose of 260 mg/m² and cisplatin at a dose of 75mg/m² followed by CCRT. The primary endpoint was objective response rate (ORR) at 2 weeks after the completion of induction therapy and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Between January and October 2024, 29 patients were enrolled, with a median age of 58 years (range 32–70). All patients were ECOG performance status of 1. Of these, 26 had squamous cell carcinoma, and 3 had adenocarcinoma. FIGO stages included stage II (9 [31.0%]), III (18 [62.1%]), and IVA (2 [6.9%]). As of January 19, 2025, 26 patients completed CCRT. Median PFS and OS were not reached. At 2 weeks post-induction therapy, ORR was 93.1% (27 PR, 2 SD). Thirteen patients underwent evaluation at 3 months post-CCRT, all achieving CR (100%). Grade 3–4 treatment-related adverse events occurred in 10.3% of patients (3/29), including leukopenia (n=2) and primary adrenal insufficiency (n=1) during induction therapy. Conclusions: Cadonilimab combined with chemotherapy as induction therapy shows promising anti-tumor activity and manageable safety profile in LACC patients. These findings suggest the potential of induction chemo-immunotherapy followed by CCRT and warrants further follow-up. Clinical trial information: NCT06511726 .