FDA Grants Approval to Lirafugratinib for Advanced Cholangiocarcinoma with FGFR2 Alteration

The FDA has approved lirafugratinib (Lyrfigtu), an investigational oral FGFR2 inhibitor, as a treatment for patients with previously treated unresctable, locally advanced or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 gene fusion or other rearrangement, according to a news release from the FDA.¹

Lirafugratinib has been recommended at a dose of 70 mg orally once daily until disease progression or unacceptable toxicity. The prescribing information also include warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.

What data support the use of lirafugratinib in FGFR2-altered cholangiocarcinoma?

The NDA is supported by findings from the phase 1/2 ReFocus trial (NCT04526106), an open-label, first-in-human study evaluating lirafugratinib in patients with advanced or metastatic solid tumors harboring FGFR2 alterations. Results from the trial were most recently shared at the 2026 ASCO Gastrointestinal Cancers Symposium.² Among FGFR inhibitor–naive patients with CCA who had received prior chemotherapy, lirafugratinib produced a confirmed objective response rate of 46.5% (95% CI, 37.1%-56.1%) by independent review committee assessment, with a disease control rate of 96.5% (95% CI, 91.3%-99.0%). The median duration of response was 11.8 months (95% CI, 7.5-13.0), and median progression-free survival and overall survival were 11.3 months (95% CI, 9.2-14.8) and 22.8 months (95% CI, 18.1-27.2), respectively.

Patients in the CCA cohort received a continuous oral dose of lirafugratinib at 70 mg once daily. The safety profile was consistent with on-target FGFR2 inhibition, and adverse effects observed in the trial were managed through dose adjustments.

What is the regulatory history of lirafugratinib?

Previously, in March 2026, the FDA granted priority review to the agent in this indication and set a Prescription Drug User Fee Act (PDUFA) target action date of September 27, 2026.³ Elevar submitted the new drug application for lirafugratinib in January 2026.⁴ Elevar has also submitted a marketing authorization application to the European Medicines Agency seeking approval of lirafugratinib for the same indication.⁵

What is lirafugratinib and how does it work?

Lirafugratinib is a potent, selective, and irreversible oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in CCA and other solid tumors. FGFR2 is 1 of 4 members of the FGFR family, a group of closely related proteins with highly similar sequences and properties; lirafugratinib's selectivity for FGFR2 over the other family members is intended to differentiate it from earlier FGFR inhibitors. CCA, also known as bile duct cancer, is a rare malignancy, with approximately 8000 new cases diagnosed annually in the US.

What else is being explored with lirafugratinib?

Beyond the CCA indication under review, lirafugratinib is being evaluated in the phase 2 ReFocus202 trial (NCT07359820), which is enrolling patients with previously treated, advanced or metastatic solid tumors other than CCA that harbor an FGFR2 fusion or rearrangement and who have not received a prior FGFR inhibitor.⁶

References

1. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. News release. FDA. September 23, 2026. Accessed September 23, 2026. https://tinyurl.com/mst6kcav
2. Hollebecque A, Borad MJ, Lu P, et al. Efficacy and safety of lirafugratinib in FGFRi-naive cholangiocarcinoma (CCA) patients harboring FGFR2 fusions/rearrangements (FGFR2 f/r). J Clin Oncol. 2026;44(suppl 2):476. doi:10.1200/JCO.2026.44.2_suppl.476
3. Elevar seeks FDA approval for FGFR2 inhibitor in bile duct cancer. News release. Elevar Therapeutics. Published January 20, 2026. Accessed September 23, 2026. https://tinyurl.com/yhx9ty9v
4. Elevar Therapeutics announces FDA acceptance for review of new drug application for lirafugratinib as second-line cholangiocarcinoma treatment. News release. Elevar Therapeutics. March 30, 2026. Accessed September 23, 2026. https://tinyurl.com/4a3cu27c
5. Elevar Therapeutics submits marketing authorization application to European Medicines Agency for lirafugratinib as a treatment for patients with advanced/metastatic cholangiocarcinoma (CCA) harboring FGFR2 fusions or rearrangements. News release. Elevar Therapeutics, Inc. September 15, 2026. Accessed September 23, 2026. https://tinyurl.com/4s84457m
6. A study of lirafugratinib in non-CCA solid tumors with FGFR2 fusion or rearrangement (ReFocus202). ClinicalTrials.gov. Updated September 3, 2026. Accessed September 23, 2026. https://tinyurl.com/ydp333tn