(859) The FOCUS19 study: Efficacy of an oral PD-L1 inhibitor combined with an oral FGF19 in advanced hepatocellular carcinoma after 1st+ line treatment

Introduction/Rationale: Systemic anti-tumor therapies include molecular targeted therapy, immunotherapy, chemotherapy, and traditional Chinese medicine (TCM) treatment, among others. Despite significant progress, these treatments still fall short of delivering long-term survival benefits, thus creating an urgent need for more effective therapeutic options. Fibroblast Growth Factor Receptor 4 (FGFR4) belongs to the FGFR family, is highly expressed in the liver, and its ligand is Fibroblast Growth Factor 19 (FGF19). ABSK-011 is a highly selective, small-molecule FGFR4 inhibitor, and ABSK043 is an orally bioavailable, highly selective, and highly potent small-molecule PD-L1 inhibitor.

Methods: This study is a single-center, non-randomized, open-label, prospective, exploratory clinical trial. The primary objective of this study is to evaluate the safety and tolerability of ABSK-011 combined with ABSK043 in patients with unresectable or metastatic hepatocellular carcinoma who have FGF19 overexpression and have previously received systemic treatment.

Results: This study plans to enroll 20 patients. As of November 2025, seven patients have been enrolled, showing good safety and tolerability, with no treatment-related adverse events (TRAEs) of Grade $\ge 3$. Patients reported no discomfort other than diarrhea. Among the seven patients who had progressed after at least first-line treatment (60% of patients had experienced multiple 2nd-line therapies), four patients achieved a Partial Response (PR), one had Progressive Disease (PD), and two had Stable Disease (SD). The Objective Response Rate (ORR) was 57.1%, and the Disease Control Rate (DCR) was 85.1%.

Conclusion: The combination of ABSK-011 and ABSK043 showed good safety and tolerability, as well as good disease control, in patients with unresectable or metastatic hepatocellular carcinoma who have FGF19 overexpression and have previously received systemic treatment.