Abstract CT172: Updated efficacy and safety data for cadonilimab plus regorafenib as second-line or later therapy in advanced hepatocellular carcinoma (aHCC)

Abstract Background: Our previous study (2023 ASCO Abstract #e16154) highlighted the safety of combining Cadonilimab and Regorafenib for patients (pts) with hepatocellular carcinoma (HCC) as a second-line or later therapy. Cadonilimab, a bispecific PD-1/CTLA-4 antibody, and Regorafenib, a multi-targeted tyrosine kinase inhibitor (TKI) approved for second-line aHCC, have demonstrated encouraging safety and efficacy profiles. Given the limited treatment options for aHCC, particularly in heavily pretreated patients, this combination holds promise for improving clinical outcomes while maintaining a manageable safety profile. This abstract presents detailed efficacy and safety results of the combination therapy (NCT05644379). Methods: The study enrolled patients with aHCC who received Cadonilimab combined with Regorafenib as second-line or later treatment at Tianjin Cancer Hospital Airport Hospital. It was a retrospective study that collected clinical data from these patients from October 2022 to September 2024. Each patient received at least three cycles of combined treatment before the initial efficacy evaluation. The primary endpoint was safety, while secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Results: Among 30 aHCC pts treated with Cadonilimab plus Regorafenib, 27 were analyzed for initial treatment efficacy (3 withdrew consent). The median age was 58, with 85.2% male. At diagnosis, most had an ECOG performance status of 0 and Child-Pugh A liver function. High risk factors for HCC included MVI (3 pts), ≥3 tumor lesions (10 pts), tumor diameter ≥5 cm (5 pts), AFP ≥ 400ng/mL (5 pts). Six pts (22.2%) received the combination as second-line therapy, and 77.8% as third-line or later. The ORR was 14.8% (4 PR), and the DCR was 59.3% (4 PR, 12 SD). Common treatment-related adverse events (TRAEs) included thrombocytopenia (37.0%), hypoalbuminemia (29.6%), anemia (33.3%), nausea (14.8%), and infusion reactions (14.8%). No grade 4-5 TRAEs were observed. The median progression-free survival (mPFS) was 8 months, and the median overall survival (mOS) was not reached. Conclusions: The combination of Cadonilimab and Regorafenib demonstrated a favorable safety profile and manageable toxicity in aHCC, including heavily pretreated patients. Although the ORR was modest, the DCR and mPFS indicate potential clinical benefit. This finding underscores the pressing need to develop new therapeutic options for patients with aHCC who have exhausted second-line or later treatments and face limited alternatives. Citation Format: Jin Zhang, Yang Liu, Qi Qi, Yinchao Zhang, Dandan Wu, Linze Xu, Yueguo Li, Huikai Li. Updated efficacy and safety data for cadonilimab plus regorafenib as second-line or later therapy in advanced hepatocellular carcinoma (aHCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT172.