89P Hepatic arterial infusion chemotherapy sequential transarterial embolization combined with lenvatinib and tislelizumab in patients with high-risk unresectable hepatocellular carcinoma: A single arm phase II trial

Hepatic arterial infusion chemotherapy (HAIC), transarterial embolization (TAE), and lenvatinib are main treatments in unresectable hepatocellular carcinoma (HCC). This study aims to evaluate the safety and efficacy of HAIC sequential TAE combined with lenvatinib and tislelizumab (an anti-PD-1) as a first-line treatment in patients with high-risk unresectable HCC. This is a single-arm, open-label, phase 2 trial (NCT05532319), which is ongoing. Eligible patients with high-risk unresectable HCC (CNLC stage Ib, II and III), ECOG performance status of 0 or 1 and adequate liver function received at least one cycle of HAIC sequential TAE (every 4 weeks) combined with lenvatinib and tislelizumab (200 mg intravenously every 3 weeks). The primary endpoint was the progression-free survival (PFS) rate at six months. Secondary endpoints included objective response rate (ORR), the proportion of patients who underwent curative treatments, significant tumour necrosis, PFS, OS and safety. Between Nov 1, 2022 and Aug 12, 2023, 35 patients with high-risk unresectable HCC were enrolled. The tumour load of 14 (40%) patients exceeds 50% of the liver volume. The PFS rate at six months was 83.6%. The ORR after one cycle of HAIC sequential TAE was 31.9% (15/47, RECIST 1.1) and 63.8% (30/47, mRECIST). The ORR after two cycle of HAIC sequential TAE was 35.1% (26/40, RECIST 1.1) and 80.0% (32/40, mRECIST). 19 patients (54.3%) received curative treatment after reaching partial response, including 10 (28.6%) curative hepatic resection, 6 (17.1%) radiotherapy, 2 (5.7%) radiofrequency ablation and 1 (2.9%) liver transplantation. Significant tumour necrosis was observed in 100% tumours based on postoperative histopathology in patients who received completed hepatectomy. Median PFS and OS were not reached. Most adverse events were grade 1 or 2. The most common were thrombocytopenia (22.9%), alanine aminotransferase elevating (20%) and serum albumin decreasing (17.1%). HAIC sequential TAE combined with lenvatinib and tislelizumab is a safe and effective treatment modality in patient with high-risk unresectable HCC.