Neoadjuvant tislelizumab combined with lenvatinib plus transcatheter arterial chemoembolization in resectable hepatocellular carcinoma with high-risk of recurrence: A prospective, single-arm, phase II trial.

e16242 Background: Currently, more than 55% of liver cancer patients have recurrence within 1 years after radical surgery. However, there is no standard treatment of neoadjuvant therapy for resectable HCC patients. This study aimed to explore the efficacy and safety of the triple therapy Tislelizumab combined with lenvatinib plus transcatheter arterial chemoembolization (TACE) as neoadjuvant therapy in patients with resectable HCC with high-risk of recurrence. Methods: This prospective, single-arm, phase II trial (ChiCTR2200059574) enrolled patients with primary resectable HCC who had not received prior anti-tumor therapy. The recurrence rate was predicted to be > 50% according to the risk predictor (http: //www. asapcalculate. top/Cal2ch. html) of early recurrence before surgery. TACE will be performed once on Day 1. Tislelizumab (an anti-PD-1 antibody, 200 mg) intravenously once every 3 weeks and lenvatinib (body weight ≥ 60 kg, 12 mg;< 60 kg, 8 mg) orally daily was initiated 3 days after TACE treatment. Surgery was performed after two cycles of neoadjuvant treatment. After 4-6 weeks of surgery, patients continued to receive tislelizumab and lenvatinib for 6 months to 1 year. Primary endpoint was adverse events (AE) and major pathological reactions. Secondary endpoints were objective response rate (ORR) by mRECIST, relapse-free survival (RFS) and overall survival (OS). Results: From April 2022 to August 2023, 19 patients (median age, 55 years) were enrolled, all Child-Pugh A and ECOG PS 0, mostly males (89. 5%) and HBV infection (94. 7%). According to mRECIST, the ORR was 94. 7% (18/19, CR 2, PR 16), and the DCR was 94. 7% too (18/19, CR 2, PR 16, SD 0). In 19 patients, 14 patients had received surgical treatment (R0 resection rates were 100%), 12 patients (12/14, 85. 7%) achieved major pathological reaction (necrosis≥90%), and 2 patients (2/14, 14. 3%) achieved complete pathological response. For those patients who did not undergo surgery, 3 of them refused surgery, and 2 patients lost the chance of surgery because of disease progression and high ICG R-15, respectively. At the end of the last follow-up (January 20, 2024), tumor recurrence was detected in 2 patients after surgery. The 12-month RFS rate and OS rate were 80. 2% (95% CI: 40. 4%-94. 8%) and 94. 7% (95% CI: 68. 1%-99. 2%), respectively. Median RFS and OS were not reached. No grade 3 or above AE were observed. Conclusions: Tislelizumab, lenvatinib, and TACE were safe and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: ChiCTR2200059574.