FAITH trial: Feasibility and safety of anlotinib plus benmelstobart in patients with previously immunotherapy treated intermediate-to-advanced hepatocellular carcinoma—Amulticenter, single arm, prospective phase Ⅱ trial.

e16225 Background: In recent years, immune checkpoint inhibitors (ICIs) combined with targeted therapies have become the preferred first-line standard treatment for advanced hepatocellular carcinoma (HCC). However, the optimal second-line treatment for HCC following ICIs failure remains undefined. Benmelstobart, a novel PD-L1 inhibitor, has shown promising antitumor activity when combined with anlotinib, an antiangiogenic agent, in the treatment of second-line advanced HCC (NCT03825705). Consequently, FAITH study aimed to evaluate the efficacy and safety of anlotinib plus benmelstobart in patients with previously ICIs treated intermediate-to-advanced HCC clinically. Methods: This is a multi-center, single-arm, prospective phase II study. Intermediate-to-advanced HCC patients who failed the previous ICIs treatment were recruited. Eligible patients received anlotinib (10mg, po, d1-14, q3w) and benmelstobart (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) (RECIST v1.1). Secondary endpoints included ORR (mRECIST), progression free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results: From December 2023 to January 2025, a total of 18 patients were enrolled. The median age was 54 years (range: 36-70 years), and 15 patients (83.3%) were male. Seven patients (38.9%) had an ECOG performance status of 1, and 15 (83.3%) patients had Child-Pugh A liver function. Fifteen patients (83.3%) had BCLC (Barcelona Clinic Liver Cancer) stage of C and three (16.7%) of B. Previous treatments included vascular endothelial growth factor inhibitors plus ICIs treatment (9 patients, 50.0%), tyrosine kinase inhibitors combined with ICIs (5 patients, 27.8%), cytotoxic T lymphocyte antigen 4 inhibitors plus ICIs (3 patients, 16.7%), and ICIs alone (1 patient, 5.6%). Fourteen patients (77.8%) were HBV-positive. Among the 14 evaluable patients, 1 (7.1%) achieved partial response, 11 (78.6%) had stable disease, and 2 (14.3%) experienced progressive disease. The ORR was7.1%, and the DCR was 85.7%. Among all 18 patients, 11 (61.1%) experienced treatment-emergent adverse events (TEAEs), with 4 (22.2%) reporting grade ≥3 TEAEs, included neutropenia (5.6%), thrombocytopenia (5.6%), bleeding (5.6%), and elevated bilirubin (5.6%). Conclusions: Anlotinib combined with benmelstobart demonstrated potential efficacy and acceptable safety profile in patients with intermediate-to-advanced HCC who failed prior ICI therapies, which is worthy of further exploration with continuous recruitment of the study subsequently. Clinical trial information: NCT06031480 .