FDA Grants Fast Track Designation to Irpagratinib in FGF19-Overexpressed HCC

The FDA has granted fast track designation to irpagratinib (ABSK-011) for the treatment of patients with hepatocellular carcinoma (HCC) harboring FGF19 overexpression, according to a press release from the developer, Abbisko Therapeutics.¹

This regulatory milestone aims to expedite the development and review of the highly selective, small-molecule FGFR4 inhibitor for a molecularly defined subgroup that accounts for approximately 30% of the global HCC population and typically faces a poor prognosis.

Clinical Efficacy and Safety

The designation is supported by clinical data from a phase 1 study (NCT04906434) evaluating irpagratinib as a monotherapy in this patient population.² In the monotherapy cohort presented in a poster at the 2024 European Society for Medical Oncology (ESMO) Congress, irpagratinib demonstrated significant antitumor activity in patients in which prior therapy had failed them, including immune checkpoint inhibitors (ICIs) and multi-targeted kinase inhibitors (mTKIs).

Among 29 evaluable patients with FGF19-overexpressing HCC who were pretreated with both ICIs and mTKIs and received 220 mg of irpagratinib twice daily, the investigator-assessed overall response rate (ORR) was 44.8%. The disease control rate (DCR) in this heavily pretreated population reached 79.3%. Efficacy results also included a median duration of response (DOR) of 7.4 months and a median progression-free survival (PFS) of 5.5 months (95% CI, 3.7-7.4). Investigators noted that the responses were durable, with the longest observed response lasting 16.4 months.

Across all cohorts, which included dose levels from 160 mg to 300 mg, the ORR and DCR were 34.8% and 72.1%, respectively. The only complete response was observed in the 160 mg twice daily cohort.

Treatment-emergent adverse events (TEAEs) occurred in 100% of patients enrolled in the trail, with grade 3 or higher events in 37.8%. Further, treatment-related adverse events (TRAEs) led to dose reduction, dose discontinuation, and death in 10.8%, 4.1%, and 0%, respectively. The most common TRAEs across all dose levels were alanine aminotransferase increased (75.7%), diarrhea (70.3%), aspartate aminotransferase (59.5%), and hyperphosphataemia (47.3%).

In the poster, the study authors wrote, “Both 160 mg [twice daily] and 220 mg [twice daily] dosing of irpagratinib demonstrated manageable safety profile and promising efficacy in pre-treated FGF19-[overexpressing] HCCs, and 220 mg [twice daily] showed better survival benefits. Notably, 220 mg [twice daily] of irpagratinib exhibited 44.8% ORR and 5.5-month median PFS in heavily treated patients who had received both ICI and mTKI, which supports further late-stage development of irpagratinib in such population with huge unmet medical need.”²

At the time of data presentation, the phase 1 ABSK-011-101 study enrolled a total of 122 patients with HCC who were FGF19-overexpressing and had BCLC stage B or C, Child-Pough score of 5 to 7, and prior treatments. Irpagratinib was given either once daily or twice daily; in the escalation part, patients received from 60 mg to 400 mg once daily or 160 mg to 300 mg twice daily.

The objective of the study was to evaluate the preliminary efficacy, safety, and tolerability of irpagratinib in patients with advanced solid tumors. Secondarily, investigators also sought to determine the maximum tolerated dose and recommended phase 2 dose of irpagratinib.

Additional Information

Updated results from a phase 2 study (NCT05425940), which evaluated irpagratinib in combination with atezolizumab (Tecentriq), were presented at the 2025 ESMO Gastrointestinal Cancers Congress.³ In this trial, the efficacy was consistent across treatment lines, with an ORR of 50.0% in patients who were treatment-naïve and 52.9% in those previously treated with ICIs. The median PFS for the combination was reported at 7.0 months or longer, suggesting that the addition of an FGFR4 inhibitor may enhance the activity of PD-L1 blockade in this biomarker-positive population.

Previously, in May 2025, the Center for Drug Evaluation of China’s National Medical Products Administration granted breakthrough therapy designation to irpagratinib.

References

1. Abbisko Therapeutics announces U.S. FDA fast track designation for irpagratinib (ABSK-011). News release. Abbisko Therapeutics. February 10, 2026. Accessed February 10, 2026. https://tinyurl.com/4rce38xy
2. Chen X, Yen CJ, Huang P, et al. Updated safety and efficacy of irpagratinib (ABSK011) in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a phase 1 study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 983P.
3. Cheng Q, Zhang Y, Wang J, et al. Irpagratinib (ABSK-011) plus atezolizumab in first-line (1L) and immune checkpoint inhibitors (ICIs) treated advanced hepatocellular carcinoma (HCC) with FGF19 overexpression (+): updated results of the phase II ABSK-011-201 study. Presented at: 2025 ESMO Gastrointestinal Cancers Congress. July 2-5, 2025. Barcelona, Spain. Abstract 149MO.