Irpagratinib Gains FDA Fast Track Status in FGF19-Overexpressing Advanced HCC

The FDA has granted fast track designation to the FGFR4 inhibitor irpagratinib (ABSK-011) for the treatment of patients with advanced hepatocellular carcinoma (HCC) overexpressing FGF19 who have previously received immune checkpoint inhibitor (ICI) and multitargeted kinase inhibitor therapy.¹

Fast track status is intended to facilitate the development and expedite the review of investigational therapies addressing serious conditions with unmet medical needs. Approximately 30% of HCC tumors overexpress FGF19, a subgroup associated with aggressive disease and poorer prognosis.² These features underscore the rationale for investigation into biomarker-driven therapeutic strategies targeting the FGF19–FGFR4 axis such as irpagratinib, a highly selective small-molecule inhibitor of FGFR4.

The agent also holds breakthrough therapy designation from China’s National Medical Products Administration (NMPA), awarded in 2025.

Supporting Clinical Evidence

The FDA’s decision is based on positive data from a phase 1 trial (NCT04906434) evaluating the safety, tolerability, and pharmacokinetics of irpagratinib monotherapy in patients with advanced solid tumors.³ The study enrolled patients across sites in the United States, China, and Taiwan.

Results presented at the 2024 European Society for Medical Oncology (ESMO) Annual Congress showed evidence of clinically meaningful antitumor activity and favorable safety with irpagratinib monotherapy in this pretreated patient population. Specifically, the objective response rate (ORR) was 46.7%, and the median progression-free survival (PFS) of the population reached 5.5 months.¹

Of the evaluated dose levels, 220 mg twice daily was selected as the recommended dose for expansion and further efficacy evaluation in later trials.

Ongoing Studies of Irpagratinib

Carrying forth the encouraging early-phase results, a pivotal 2-part phase 2 registration study (NCT05441475) was initiated in China. Here, irpagratinib is being investigated in combination with atezolizumab (Tecentriq) in both treatment-naive and pretreated patients with advanced or unresectable HCC overexpressing FGF19.⁴ As of the latest data cut-off on November 19, 2024, a total of 33 patients were enrolled: 15 treatment-naive patients and 18 pretreated patients. Sixteen of the 18 patients had been treated with prior ICI therapy.

At a median follow-up of 7.1 months, both treatment-naive and pretreated groups had achieved ORRs exceeding 50% (50.0% and 52.9%, respectively).⁵ Further, the respective median PFS for the treatment-naive and pretreated groups were 7.0 months (95% CI, 2.8-not evaluable [NE]) and 8.3 months (95% CI, 1.6-NE). No new safety signals were observed; the most common treatment-related adverse events included alanine aminotransferase increase, aspartate aminotransferase increase, diarrhea, blood bilirubin increase, hyperphosphatemia, and platelet count reduction. These data were presented at the 2025 ESMO Gastrointestinal Cancers Congress.

Irpagratinib represents one of the first targeted agents in HCC development explicitly linked to a molecular biomarker, reflecting a broader shift toward precision oncology in liver cancer. Ongoing and future randomized studies, to be facilitated by the fast track program, will be essential to define the agent’s clinical utility and confirm benefit for this biomarker-defined population.

REFERENCES

1. Abbisko Therapeutics' FGFR4 inhibitor irpagratinib granted FDA fast track designation for advanced HCC patients with FGF19 overexpression previously treated with ICIs and mTKI therapies. News release. Abbisko Therapeutics. February 10, 2026. Accessed February 11, 2026. https://tinyurl.com/3v9r7xky

2. Chen X-P, Yen CJ, Huang P, et al. 983P Updated safety and efficacy of ABSK-011 in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a phase I study. Ann Oncol. 2024;35:S671. doi:10.1016/j.annonc.2024.08.1043

3. A study to assess the safety, tolerability, and pharmacokinetics of ABSK-011 in patients with advanced solid tumor. ClinicalTrials.gov. Updated November 12, 2025. Accessed February 10, 2026. https://clinicaltrials.gov/study/NCT04906434

4. A phase 2, open-label study of ABSK-011 combined atezolizumab in HCC patients. ClinicalTrials.gov. Updated September 26, 2022. Accessed February 11, 2026. https://clinicaltrials.gov/study/NCT05441475

5. Cheng Q, Zhang Y, Wang J, et al. 149MO 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. Ann Oncol. 2025;36:S63. doi:10.1016/j.annonc.2025.05.162