Neoadjuvant immune-checkpoint blockade therapy in combination with TACE for resectable hepatocellular carcinoma with high recurrence risk: A phase II, single-arm clinical trial (MORNING).

Abstract

e16304 Background: Prognoses for patients with hepatocellular carcinoma (HCC) remain suboptimal due to the high recurrence rates following curative intended hepatectomy. In this study, we evaluated the safety and efficacy of neoadjuvant Cadonilimab (a bi-specific antibody targeting PD-1 and CTLA-4) in combination with transarterial chemoembolization (TACE) for patients at high risk of recurrence. Methods: In this phase II, single-arm trial, resectable HCC (BCLC stage A/B) participants were enrolled. Patients should meet at least one of the following high-risk criteria: a) Multiple tumors or satellite lesions (≥2); b) tumor diameter > 5cm (single tumor); c) AFP ≥ 400 ug/L; d) Predicted to be positive by the Microvascular invasion prediction model of our center according to preoperative imaging. All patients received two cycles of Cadonilimab(10mg/kg, Q3W) following TACE treatment. After resection, patients received additional 12 months of Cadonilimab (10mg/kg, Q3W). The primary endpoint was the major pathological response(MPR, defined as ≥90% necrosis of the resected tumour),while the secondary endpoints include objective response rate (ORR), one-year recurrence rate and safety. Results: Until December 13th, 2024, a total of 30 patients were enrolled and underwent successful resection. Among the patients, 25(83.3%) were male, with the mean age of 54 years. Fourteen (46.7%) patients had multiple tumors, and 22(73.3%) had tumors larger than 5cm. Nineteen (63.3%) achieved MPR, while26(86.7%) exhibited 70% or greater tumour necrosis. According to mRECIST , the ORR was 83.3% (25/30) and DCR was 100%(30/30). Of these patients, 2 patients achieved complete response (CR), and 23 patients achieved partial response (PR). Additionally, 27 patients maintained stable decease, while only 3 patients received PR as assessed by RECIST1.1. The 1-year recurrence-free survival rate of entire cohort was 90%. Notably, patients who did not achieve MPR had a higher recurrence rate(27.3% vs. 5.3%). Simultaneously, this subgroup also demonstrated a lower ORR (54.6 vs. 100%) per mRECIST. The most common TRAEs of any grade were ALT/AST increase (90%), abdominal pain (86.7%) and bilirubin increase (56.7%). Four patients experienced grade 3 adverse events, including infusion reaction (n = 2), and white blood cell decreased (n = 2). Notably, abdominal pain and fever were more frequently associated with TACE. No grade 4 or 5 events were observed. The incidence of immune-related adverse event (irAE) was 23.3%. Furthermore, it was observed that patients who experienced irAEs tended to demonstrate a better pathological response. Conclusions: Cadonilimab combined with TACE as a neoadjuvant therapy demonstrated acceptable safety profile and promising efficacy for high risk HCC patients. Clinical trial information: NCT05578430 .