Neoadjuvant hepatic arterial infusion chemotherapy (HAIC) plus tislelizumab (Tisle) combined with adjuvant tisle as a perioperative therapy for hepatocellular carcinoma (HCC) at high-risk of recurrence: A single-arm, phase II study.

e16284 Background: Adjuvant therapy alone after curative resection has failed to reduce recurrence or improve survival in HCC patients (pts) at high risk of relapse. A perioperative strategy integrating neoadjuvant and adjuvant treatment may improve outcomes. HAIC combined with PD-1 inhibition has demonstrated synergistic antitumor activity with favorable safety in HCC. This study evaluates a perioperative “sandwich strategy” consisting of neoadjuvant HAIC plus Tisle, followed by surgery and adjuvant Tisle, in high-risk resectable HCC. Methods: This ongoing prospective single-arm phase II trial (NCT06467799) plans to enroll 39 pts, with resectable CNLC Ib/IIa HCC beyond Milan criteria (single tumor > 5 cm or 2–3 tumors with largest > 3 cm), without portal vein thrombus, extrahepatic metastasis, or prior treatment. Eligible pts receive 2 cycles of neoadjuvant FOLFOX-HAIC plus Tisle, followed by surgery upon confirmed resectability, and 4 cycles of adjuvant Tisle. A Bayesian optimal phase II design was used, with 1-year recurrence-free survival (RFS) as the primary endpoint. The historical 1-year RFS rate for surgery alone was 60%, and 80% for the experimental group. With a one-sided type I error of 0.05, power of 0.9, and 10% dropout, the total sample size was 39. Interim analyse was performed at 10, 20, 30, 39 pts, maintaining an alpha of 0.05 and power of 0.86. Secondary endpoints include objective response rate (ORR, mRECIST), pathologic complete response(pCR), overall survival (OS) and safety. Results: As of January 1, 2026, 32 pts were enrolled; 26 completed neoadjuvant therapy and six remained on neoadjuvant treatment. The ORR to neoadjuvant therapy was 53.8%. Of the 26 patients completing neoadjuvant therapy, 25 underwent planned surgical resection. The pCR rate was 24.0%, and microvascular invasion was observed in only one patient. Sixteen pts had completed adjuvant therapy. With a median follow-up of 6.3 months, no disease recurrence or death was observed. The most common treatment-related adverse events were grade 1–2 included decreased appetite and vomiting, with no grade ≥3 adverse events reported. Conclusions: Perioperative HAIC plus Tisle demonstrated favorable safety and promising antitumor activity in pts with high-risk HCC. Comprehensive long-term outcoms, safety, pathological, and clinical response data will be provided. Clinical trial information: NCT06467799 . Baseline tumor characteristics and efficacy of neoadjuvant therapy. parameter All （n=32） Tumor size (mean, cm) 7.5 Tumor N.12-3 68.8 %31.2% mRECIST evaluable for neoadjuvant treatment (n=26) CRPRSDPD 5/269/2612/260 ORR(%) 53.8% DCR(%) 100.0% pCR(%) 24.0%(6/25) MVI(%) 4.0%%(1/25)