187P - Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus transhepatic arterial infusion chemotherapy (HAIC) for resectable multinodular CNLC Ib/IIa hepatocellular carcinoma (Car-Hero)

Background

The recurrence rate of hepatocellular carcinoma (HCC) remains high and multinodular HCC is a well-defined high-risk factor. This trial is to evaluate the safety and efficacy of cadonilimab plus HAIC as a neoadjuvant management for the resectable multinodular HCC with CNLC stage Ⅰb/Ⅱa.

Methods

In this ongoing single-center, phase 2, open label, prospective cohort clinical trial, eligible patients (pts) were randomly assigned (1:1:1) to 3 arms and receive neoadjuvant therapy: (A) 2 cycles of cadonilimab (6mg/kg Q2W); (B) once HAIC with FOLFOX regimen followed by 2 cycles of cadonilimab; (C) once FOLFOX-HAIC. Pts receive scheduled surgery on day 21-28 and adjuvant HAIC one month after surgery. Primary endpoints were major pathologic response (MPR defined as ≤50% residual living tumor) and 1-year RFS rate. Secondary endpoints included ORR, DCR and TRAEs.

Results

From January 4 to August 20, 2023, 18 pts were enrolled and 16 pts have received scheming hepatectomy (5 pts in Arm A, 9 pts in Arm B, 2 pt in Arm C). Remarkably, almost all (8/9) pts in Arm B achieved MPR and some pts demonstrated focal heterogeneity—one lesion achieved pathologic complete response, while another got non-/partial response. No obvious tumor necrosis in Arm A and C, but the inflammatory infiltrating and fibrosis area seemed to increase in some HCC lesions. 3 pts in Arm B (3/9) achieved PR and DCR was 100% per RECIST 1.1. The most common TRAEs in Arm B and C were increased ALT, AST (Grade 1-3) and bilirubin (Grade 1), which mainly resulted from HAIC and can be improved by routine liver protection treatment. Main TRAEs observed in Arm A was increased AST (Grade 3). Two pts in Arm A and B delayed scheduled surgery for 3 weeks due to increased ALT/AST. One pt experienced postoperative controllable pneumonia which may relate to novel coronavirus (2019-nCoV) and cadonilimab. One pt experienced postoperative severe but curable bacterial hepatic abscess related to bilioenteric anastomosis and diabetes mellitus.

Conclusions

This study preliminarily demonstrated that neoadjuvant cadonilimab plus FOLFOX-HAIC had a promising antitumor activity and a manageable safety for the resectable multinodular HCC.

Clinical trial identification

ChiCTR2200067161; Chinese Clinical Trial Registry; 2022-12-28.

Editorial acknowledgement

The authors acknowledge to Akeso Biopharma Ltd. for their drugs and writing supports.

Legal entity responsible for the study

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University.

Funding

Akeso Biopharma Ltd.

Disclosure

All authors have declared no conflicts of interest.