A phase I study of adoptive tumor-infiltrating lymphocyte (TIL, BST02) therapy in patients with advanced liver cancer.

e16198 Background: Liver cancer (LC) is the leading cause of cancer-related death in patients around the world. Treatment options for advanced LC are limited with poor overall survival. Exploring new therapy strategies to improve clinical benefits for advanced LC is essential. Adoptive cell therapy with TIL has been successfully approved for advanced melanoma treatment with durable long-term responses after conventional therapies. This study aims to explore the safety and efficacy of adoptive TIL transfer (BST02) in advanced LC patients (NCT06526832). Methods: Patients having histologically or cytologically confirmed advanced LC were enrolled. All patients have received more than three standard therapies, including systemic therapy with tyrosine kinase inhibitors or anti-VEGF combine with anti-PD-1/PD-L1 and regional chemotherapy with transhepatic arterial chemotherapy and embolization (TACE) or hepatic artery infusion chemotherapy (HAIC). Tumor tissues were freshly collected for BST02 manufacturing and products were released based on safety and efficacy criteria. Patients received lymphodepletion chemotherapy (cyclophosphamide, 250 mg/m 2 × 3 days and fludarabine, 25 mg/m 2 × 3 days) before BST02 administration (cohort 1: 5 × 10 9 viable cells, 3 patients; cohort 2: 2 × 10 10 viable cells, 6 patients) followed by IL-2 infusion (total dose: 120 million IU, ≤ 12 doses, q12h). The incidence of adverse events (AEs) and dose-limiting toxicities (DLTs) were recorded. Tumor responses were assessed by mRECIST criteria. Results: As of January 10, 2025, TILs were manufactured successfully for 3 patients in cohort 1 and 2 patients in cohort 2. The culture period ranged from 20 to 26 days (median value: 25 days). Percentages of CD8 + T cells ranged from 6.82% to 36.4% (median value: 19.3%). Levels of IFNγ release upon co-culture with target cell line (modified-SK-Hep-1) ranged from 18.9 ng/mL to 53.7 ng/mL (median value: 21.0 ng/mL). The first 3 patients (cohort 1) were successfully infused with BST02 and post-treated with IL-2. No DLTs occurred in cohort 1. 50.9% (28/55) adverse effects (AEs) were related to lymphodepletion and IL-2 treatment, 45.5% (25/55) AEs were related to BST02 infusion (≤ Grade 3). All AEs were recovered within 2 weeks post BST02 infusion. Furthermore, in cohort 1, 2 out of 3 patients had baseline and post-infusion disease evaluations. BST02 demonstrated a 100% (2/2) disease control rate (DCR) and 50% (1/2) objective response rate (ORR). In the best response patient, durable significant shrinkages of multiple lesions were observed (57.1% reduction of multiple target lesions in the liver, and 51.8% reduction of the portal vein tumor thrombus at 84 days post infusion). Conclusions: BST02 is well tolerated in advanced LC patients and demonstrates a robust anti-tumor efficacy at the dose of 5 × 10 9 viable cells, which supports the further clinical investigation. Clinical trial information: NCT06526832 .