Abstract 171P
Background
FGF19 overexpression (+) is in ∼ 30% of HCC. ABSK-011, a highly selective and potent FGFR4i, has demonstrated promising response rate and manageable safety profile for FGF19+ HCC in phase 1 study. This phase 2 open-label study (NCT05441475) is the first study to evaluate the safety and preliminary efficacy of FGFR4i plus immune checkpoint inhibitor (ICI) in FGF19+ HCC.
Methods
ABSK-011 was given QD or BID orally in 21-day cycles and atezolizumab (atezo) was given 1200 mg IV Q3W. Patients (pts) ≥18 years old with advanced HCC, ECOG PS≤1, and adequate organ function were eligible. Tumor assessments were every 6 weeks.
Results
As of 18 Mar 2024, 36 pts were dosed with ABSK-011 180 mg QD (N=6), 320 mg QD (N=6), 160 mg BID (N=8) and 220 mg BID (N=16). Among the 36 pts, the mean age was 51.2 years old with 77.8% male, 63.9% ECOG PS 1, 83.3% with prior therapies. DLT was observed in only 1 pt (160 mg BID): alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased with blood bilirubin increased and alkaline phosphatase increased. Safety results indicated that 30 pts (83.3%) experienced treatment-related adverse events (TRAEs) for ABSK-011 or atezo, and grade 3 TRAEs reported in ≥2 pts included ALT increased (6/36, 16.7%) and AST increased (3/36, 8.3%), majority of which were transient and improved after dose interruption and/or supportive care. No grade 4/5 TRAEs. Four pts (11.1%) reported serious TRAEs, including ALT increased (3) / AST increased (2) / blood bilirubin increased (2) and haematochezia (1). Seven partial responses were reported by investigator assessment based on RECIST v1.1, including 2 responders (1 FGF19+) in 320 mg QD and 5 (all FGF19+) in 220 mg BID among the 28 efficacy-evaluable pts. 220 mg BID dosing showed encouraging efficacy with an overall response rate of 55.6% (5/9) in FGF19+ HCC. The longest duration of response (DOR) among all dose levels was 15.4 m and median DOR is not yet mature.
Conclusions
ABSK-011 in combination with atezolizumab showed encouraging anti-tumor activity and manageable safety profile which supports further development of the regimen in FGF19+ HCC and exploration of ABSK-011 based double/triple combinations in earlier lines.
Clinical trial identification
NCT05441475.
Legal entity responsible for the study
Abbisko Therapeutics Co., Ltd.
Funding
Abbisko Therapeutics Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.