Real-world efficacy and safety of cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced, recurrent, and metastatic cervical cancer.

5537 Background: Immune checkpoint inhibitors have become one of the important treatment modalities for advanced, recurrent and metastatic cervical cancer (A/R/M CC). Cadonilimab, a PD-1 and CTL-4 bispecific antibody, has showed considerable efficacy for treatment of A/R/M CC. This study aims to investigate the real-world efficacy and adverse event profile of cadonilimab in the treatment of A/R/M CC. Methods: We enrolled patients with histologically confirmed CC, who had received at least two cycles of cadonilimab for A/R/M disease and had imaging evaluation at Department of Gynecologic Oncology in Shandong Cancer Hospital and Institute in China, between July 2022 and March 2024. Efficacy including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were analyzed. Results: 96 patients treated with cadonilimab monotherapy or cadonilimab plus chemotherapy with/without radiotherapy were enrolled. The median follow-up duration was 12.5 months. The overall ORR was 69.8%, the DCR was 89.6%. (Table 1). The median PFS was 12 months (95%CI 8.4-15.6), and the median OS was not reached. The ORR of first and second line’s treatment was 77.7% and 56.6%, respectively. DCR was 91.7% and 80.0%, respectively. Among the 18 patients treated with third-line and above, four (22.2%) patients achieved CR, ORR was 72.2%, and DCR was 88.8%. Among all patients, PD-L1 positive patients had a higher ORR (74.4%, P=0.049). Comparing with non-SCC, patients with SCC had better ORR (78.6% vs.38.0%, P=0.001). It's also worth noting that, among 19 patients who had progressed on first or second line’s therapy of PD-1 monospecific antibody, cadonilimab mono or combination therapy achieved an overall ORR of 63.1% (1 CR, 11 PR) and a DCR of 94.7%, and a median PFS of 15.2 months (95%CI 5.7-24.7). Among them, 16 patients with SCC had a 100% DCR and a median PFS of 15.2 months (95%CI 5.1-25.3). The incidence of immune-related adverse events (irAEs) was 33.3%, mainly including 21 hypothyroidism (21.9%), seven hyperthyroidism (7.3%), etc. Two (2.1%) had ≥ grade 3 irAEs (one pneumonia and one myocardial injury). No death was caused by irAEs. Conclusions: Cadonilimab showed encouraging efficacy and manageable safety in the treatment of A/R/M CC in real world, even in patients with PD-L1 negative. And it also present promising disease control in patients who have progressed on previous PD-1 monospecific antibody. The best overall response, PFS and OS in first-, second-, ≥ third-line and total patients. Best overall response, PFS and OS First-line(n=48) Second-line(n=30) ≥Third-line（n=18) Total CR (%) 16.6 16.6 22.2 17.7 PR (%) 60.4 40.0 60.0 52.0 ORR (%) 77.7 56.6 72.2 69.8 DCR (%) 91.7 80.0 88.8 89.6 mPFS (months) 12.0 8.9 18.7 12.0 6-month PFS rate (%) 87.5 66.6 88.8 81.2 6-month OS rate (%) 100.0 100.0 100.0 100.0