PERI-START: a phase II trial of perioperative TACE, tislelizumab, and lenvatinib in early-stage hepatocellular carcinoma

The unsatisfactory prognosis of patients with early-stage hepatocellular carcinoma (HCC) emphasizes the urgent need for perioperative treatment to reduce recurrence after surgery. The combination of transarterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein 1 (PD-1) inhibitor has emerged as a promising treatment for unresectable HCC, yet its perioperative application was not explored. PERI-START is a prospective, single arm phase II trial which aims to investigate the efficacy and safety of TACE, tislelizumab (PD-1 inhibitor), and lenvatinib (TKI) in perioperative (neoadjuvant and adjuvant) use for resectable, high-risk HCC. Within 1 week after enrollment, TACE will be administered. Subsequently, intravenous tislelizumab will be given every 3 weeks in combination with daily oral lenvatinib. Unless disease progression occurs, liver resection will then be performed. 4-6 weeks after liver resection, tislelizumab and lenvatinib will be resumed for 6 months. The primary endpoint is the major pathological response (MPR) rate, with secondary endpoints including objective response rate (ORR), R0 resection rate, event-free survival (EFS), overall survival (OS), and adverse events (AEs).<b>Clinical trial registration:</b> ChiCTR2400085067 (www.chictr.org.cn).