A study of cadonilimab combined with regorafenib as second-line or later therapy in patients with advanced hepatocellular carcinoma (aHCC).

Abstract

e16154 Background: Current second-line treatment options for aHCC patients (pts), including single TKI or anti-PD-1+anti-CTLA4, result in limited survival benefits, objective responses or increasing concerns regarding adverse effects. An exploration of safer and more effective second-line or later therapies for aHCC is paramount. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in HCC. Previous data indicated that cadonilimab possesses an improved safety profile and an encouraging anti-tumour activity compared to combined administration of anti-PD-1 plus anti-CTLA-4 antibodies. Regorafenib was the first TKI that approved globally as a second-line treatment of aHCC. Here, we evaluated the safety of cadonilimab plus regorafenib as second-line or later therapy in pts with aHCC. Methods: The study population derived from prospectively collected retrospectively analyzed data (10/2022-02/2023) of pts treated with cadonilimab plus regorafenib as second-line or later therapy for aHCC at Tianjin Cancer Hospital Airport Hospital. The primary endpoint was safety. Results: We identified 29 pts with aHCC who received cadonilimab plus regorafenib. The median age was 59 years; 86.2% were male; 72% were ECOG PS 0; 72% had a Child-Pugh score of A at diagnosis. High risk factors for HCC included MVI (3pts), ≥3 tumour lesions (10pts), tumour diameter ≥5cm (5pts), AFP≥400ng/mL (5pts). Six pts (21%) received cadonilimab plus regorafenib in the second-line while the rest of pts (79%) received it as third-line or later. All pts previously received at least one line of immunotherapy combined with anti-angiogenic target agents. Seven pts received triple combination regimens (ICIs+TKIs/Bev+HAIC) before. At time of data extraction, no pts were assessed for efficacy due to the COVID-19 pandemic (especially the outbreak in early December 2022) and short follow-up time, we focused on the safety and tolerability in this report. Any grade treatment related adverse events (TRAEs) occurred in 24pts (83%). The most common TRAEs of any grade were hypoalbuminemia (24%), lymphocyte count decreased (21%), rash (14%), nausea (14%) and infusion reaction (14%). Only four (14%) patients experienced grade 3 TRAEs including infusion reaction (2pts), lymphocyte count decreased (1pt) and gastrointestinal hemorrhage (1pt, regorafenib related). No grade 4-5 TRAEs were observed. Conclusions: The combination of cadonilimab plus regorafenib was generally well tolerated. The prospective trail of cadonilimab combined with regorafenib as second-line or later therapy for aHCC is ongoing (NCT05644379). Although it needs to be reconfirmed, the treatment responses of some patients are encouraging (including sharp decrease in AFP level and/or reduced tumor size). Related data will be reported in the future.