Updated safety and efficacy of ABSK-011 in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a phase I study

BackgroundFGF19 overexpression (+) is in ∼ 30% of HCC with poor prognosis, and studies suggested FGF19/FGFR4 signaling axis could be a promising therapeutic target for HCC. ABSK-011, an oral, highly selective, and potent FGFR4 inhibitor, exhibited preliminary efficacy in a phase 1 trial (NCT04906434) for FGF19+ aHCC. Here we present updated results of this study.MethodsPatients (pts) with FGF19+ aHCC were treated with QD or BID, and 220 mg BID was selected as the recommended dose for expansion (RDE) to further evaluate the efficacy and safety of ABSK-011.ResultsAs of 31 Mar 2024, 109 pts were treated with ABSK-011 ranging from 60 mg to 400 mg QD (N=48), and 160 mg to 300 mg BID (N=61). 106 pts were aHCC, median age 52.5 y; 85.8% male; 67.0% ECOG PS 1; 4.7% BCLC B and 92.5% BCLC C; 68.9% Child-Pugh (CP) 5, 27.4% CP 6, and 3.8% CP 7; 96.2% with ≥1 regimen of prior systemic therapy. Dose-limiting toxicities were observed in 3 pts (2 in 400 mg QD, and 1 in 300 mg BID). Most common treatment-related adverse events (TRAEs) (>20%) were alanine aminotransferase (ALT) increased (70.6%), diarrhea (67.9%), aspartate aminotransferase (AST) increased (56.9%), hyperphosphataemia (37.6%), bilirubin increased (35.8%), total bile acids increased (21.1%) and alkaline phosphatase increased (20.2%). Majority of TRAEs were Gr 1-2 and reversible/manageable. Gr 3−4 TRAEs (>5%) included AST increased (11.0%), ALT increased (11.0%) and diarrhea (6.4%). No Gr 5 TRAE. Thirty-five aHCC pts with FGF19+ were treated at 220 mg BID. In response evaluable pts, the overall response rate (ORR) was 38.7% (12/31) and disease control rate (DCR) was 77.4% (24/31). The median progression-free survival (mPFS) was 4.7 m (95% CI: 3.5 - NE). The median duration of response (DoR) for confirmed responders was not yet mature; the longest duration was 11.1 m and this patient is still ongoing. Among pts with prior ICI treatments, comparable efficacy was found with an ORR of 40.7% (11/27) and a DCR of 77.8% (21/27).ConclusionsABSK-011 demonstrated a manageable safety profile and promising anti-tumor activity as a single agent. These findings support further development of ABSK-011 at 220 mg BID in FGF19+ aHCC with prior ICI treatments.Clinical trial identificationNCT04906434.Legal entity responsible for the studyAbbisko Therapeutics Co., Ltd.FundingAbbisko Therapeutics Co., Ltd.DisclosureAll authors have declared no conflicts of interest.