Tislelizumab as monotherapy or in sequential combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma: A prospective, phase II clinical study.

e16292 Background: Neoadjuvant immunotherapy represents a potential approach to improve the post-surgical prognosis of resectable HCC. Nevertheless, given that early-stage HCC is distinct from advanced disease, it remains uncertain whether immune-based monotherapy or combination therapy is sufficient in the neoadjuvant setting. This study aims to explore the preliminary efficacy and safety of Tislelizumab monotherapy or its sequential combination with Lenvatinib in the neoadjuvant treatment of resectable HCC. Methods: In this phase Ⅱ study (NCT05807776), enrolled HCC patients received 2 cycles of Tislelizumab (200mg, Q3W) firstly. Patients who achieved partial response (PR) or reduced stable disease (SD) directly received surgery, followed by adjuvant treatment with Tislelizumab. Patients who achieved progressive disease (PD) or increased SD continued to receive 2 cycles of Tislelizumab and Lenvatinib(8mg/d), followed by surgery and adjuvant treatment with Tislelizumab and Lenvatinib. The primary endpoint was major pathologic response rate (MPR, tumor necrosis > 70%), secondary endpoints were 1 and 2-year DFS rate, ORR, surgical delay rate and safety. Results: Up to 12 th Jun 2024, 36 patients were enrolled with a median age of 59 years. All patients were Child-Pugh class A and ECOG PS 0. 35 (97.2%) patients were BCLC stage A and 32 (88.9%) patients had HBV infection. 5 (13.9%) patients received Tislelizumab plus Lenvatinib sequentially after the first tumor evaluation according to the protocol. In the neoadjuvant setting, ORR was 16.7% per RECIST v1.1 and 30.6% per mRECIST. DCR was 91.7%. 33 (91.7%) patients underwent surgery eventually and MPR was 24.2%, including 5 (15.2%) pCR. At the data cut off (12 th Jan 2025), the median follow-up time was 14 months (95% CI: 12.82-15.18). median DFS was not reached. 1 and 2-year DFS were 73.8% and 58.5%, respectively. Treatment related AEs (TRAE) occurred in 38.9% patients. Grade 3 TRAEs occurred in 11.1% patients, including dermatomyositis (n = 1), oral mucositis (n = 1) and rash (n = 1). There was no grade 4/5 AE. Conclusions: Neoadjuvant Tislelizumab monotherapy or sequentially combined with Lenvatinib was well tolerable and showed promising efficacy in early-stage resectable HCC. Our study showed that a proportion of early-stage HCC patients could derive benefits from neoadjuvant Tislelizumab monotherapy, while the combination regimen might be a more favorable choice for some others. Further analysis on the prognostic factors of treatment response is necessary to optimize neoadjuvant therapy regimens. Clinical trial information: NCT05807776 .