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

person Li Tan Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China info_outline Li Tan, Lixia Xu, Shun-Li Shen, Dongming Li, Yunpeng Hua, Shaoqiang Li, Lijian Liang, Qiang He, Qi Zhou, Wenxuan Xie, Zebin Chen, Jian Wu, Jiaping Li, Wenzhe Fan, Wenquan Zhuang, Lili Chen, Shiting Feng, Sui Peng, Jiping Wang, Ming Kuang

Authors person Li Tan Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China info_outline Li Tan, Lixia Xu, Shun-Li Shen, Dongming Li, Yunpeng Hua, Shaoqiang Li, Lijian Liang, Qiang He, Qi Zhou, Wenxuan Xie, Zebin Chen, Jian Wu, Jiaping Li, Wenzhe Fan, Wenquan Zhuang, Lili Chen, Shiting Feng, Sui Peng, Jiping Wang, Ming Kuang Organizations Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Interventional Radiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Clinical Trials Unit, Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, Department of Surgery, Brigham and Women's Hospital, Boston, MA Abstract Disclosures Research Funding No funding sources reported Background: Prognoses of patients with hepatocellular carcinoma (HCC) remain unsatisfactory due to the high recurrence rate after curative hepatectomy. In this study, we investigated the safety and efficacy of neoadjuvant Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) in combination with transarterial chemoembolization(TACE) for patients with high recurrence risk. Methods: For this phase II, single-centre, single-arm trial, resectable HCC (BCLC stage A/B) participants were enrolled, who 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 of the patients received two cycles of Cadonilimab(10mg/kg, Q3W) after TACE treatment. After resection, patients received additional 12 months of Cadonilimab(10mg/kg, Q3W) in the adjuvant setting. The primary end-point was the major pathologic response (MPR, defined as >90% necrosis of the resected tumour), the secondary endpoints are objective response rate (ORR), one-year recurrence rate and safety. Results: Between Apr 26th, 2023, and Jan 5th, 2024, 19 patients were enrolled, 84.2% of whom were male, with the mean age of 55. 9(47.4%) patients had more than one tumor and 13(68.4%) patients had tumors larger than 5cm. All patients received neoadjuvant TACE and at least one cycle of Cadonilimab. Of the 15 patients underwent successful resection, 7(46.7%) had MPR, while 12(80%) of them had 70% or greater tumour necrosis. 11 patients had partial response and the ORR was 73.3% per mRECIST. Additionally, only one patient received a partial response, while twelve patients maintained stable decease as assessed by RECIST1.1. 19(100%) patients had treatment-related adverse events of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were ALT/AST increase (94.7%), abdominal pain (73.7%) and bilirubin increase (57.9%). 4 patients had grade 3 adverse events, including infusion reaction (2 patients), white blood cell decreased (2 patients) and fever (1 patients). The abdominal pain and fever were more relevant to TACE. No grade 4 or 5 events were observed. Conclusions: Cadonilimab combined with TACE as a neoadjuvant therapy seems to demonstrate safety and promising efficacy. Clinical trial information: NCT05578430. Tumor Response, n (%) Number of Patients (n=15) mRECIST RECIST1.1 Partial response (PR) 11(73.3%) 1(6.7%) Stable disease (SD) 4(26.7%) 12(80%) Progressive disease (PD) 0 1+ 1(pseudoprogression) ORR 73.30% 6.70% disease control rate(DCR) 100% 86.70% major pathologic response (Tumour necrosis >90%) 7(46.7%) Tumour necrosis ≥70% 12(80%) Tumour necrosis ≥50% 15(100%)