983P - Updated safety and efficacy of ABSK-011 in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a phase I study

Background

FGF19 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.

Methods

Patients (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.

Results

As 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).

Conclusions

ABSK-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 identification

NCT04906434.

Editorial acknowledgement

Legal entity responsible for the study

Abbisko Therapeutics Co., Ltd.

Funding

Abbisko Therapeutics Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.