FDA Grants Lirafugratinib Priority Review in FGFR2-Altered Cholangiocarcinoma

The FDA has granted a priority review to a new drug application (NDA) for lirafugratinib, a highly selective oral FGFR2 inhibitor, for the treatment of patients with cholangiocarcinoma (CCA) harboring FGFR2 fusions or rearrangements who have received prior therapy, according to Elevar Therapeutics.¹

The Prescription Drug User Fee Act target action date is September 27, 2026.

The NDA was supported by efficacy and safety data from the phase 1/2 ReFocus trial (NCT04526106).^1,2 In the CCA cohort of the trial, which comprised FGFR inhibitor-naive patients who had previously received chemotherapy (n = 114), lirafugratinib achieved a confirmed objective response rate (ORR) of 46.5% (95% CI, 37.1%-56.1%) per independent review committee (IRC) assessment, a disease control rate of 96.5% (95% CI, 91.3%-99.0%), and a median duration of response of 11.8 months (95% CI, 7.5-13.0). The median progression-free survival was 11.3 months (95% CI, 9.2-14.8) and the median overall survival was 22.8 months (95% CI, 18.1-27.2).²

"Lirafugratinib has established a compelling clinical profile that differentiates it from existing treatment options," Dong-Gun Kim, chief executive officer of Elevar, stated in a news release.¹ "We are very pleased with the FDA's priority review designation and focused on advancing the review process efficiently to bring this therapy to patients as quickly as possible."

ReFocus Trial

Lirafugratinib is a potent, selective, and irreversible small molecule inhibitor of FGFR2 distinguished by its high selectivity relative to other members of the FGFR family. The ongoing open-label, first-in-human, multi-part ReFocus study is exploring lirafugratinib in patients with advanced or metastatic solid tumors harboring FGFR2 alterations.

Patients in the CCA cohort received a continuous oral dose of 70 mg once daily. Eligibility required histologically or cytologically confirmed locally advanced or metastatic CCA, prior failure or intolerance of standard therapy, and an ECOG performance status of 0 or 1. The primary endpoint was confirmed ORR per RECIST v1.1 criteria; key secondary endpoints included duration of response, disease control rate, progression-free survival, overall survival, safety, and quality of life.³

The primary end point for the CCA cohort was confirmed ORR per RECIST 1.1 criteria by IRC.² Key secondary end points included DOR, DCR, PFS, OS, safety, and quality of life (QOL) as assessed by the EORTC Core QOL questionnaire.

The most common any-grade treatment-related adverse effects in the pivotal cohort included nail toxicities (87.9%), palmar-plantar erythrodysesthesia (81.9%), stomatitis (78.4%), and retinal pigment epithelial detachment (37.1%). Grade 3 or higher events for these toxicities occurred in 12.1%, 32.8%, 12.1%, and 1.7% of patients, respectively. Elevar has characterized this safety profile as predictable and manageable through dose modifications.²

The Second-Line Treatment Landscape

The current standard of care in the first line setting for advanced CCA is gemcitabine/cisplatin-based chemotherapy combined with an immune checkpoint inhibitor. For patients with FGFR2-altered CCA who progress after first-line therapy, 2 FGFR inhibitors are currently FDA-approved in the second-line setting: pemigatinib and futibatinib. Researchers are now hoping to further improve on outcomes with these agents using lirafugratinib. Randomized data directly comparing lirafugratinib to these available FGFR inhibitors in this setting are not yet available.

Elevar Therapeutics has stated that it is also evaluating lirafugratinib in ongoing studies in other FGFR2-altered solid tumors beyond CCA. Any future indications will be subject to separate regulatory review and approval.

REFERENCES

1. Elevar Therapeutics, Inc. Elevar Therapeutics announces FDA acceptance for review of new drug application for lirafugratinib as second-line cholangiocarcinoma treatment. Press release. March 30, 2026. Accessed March 30, 2026. https://tinyurl.com/22stfuv6

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. REFOCUS: a first-in-human study of highly selective FGFR2 inhibitor, RLY-4008, in patients with ICC and other advanced solid tumors ClinicalTrials.gov. Updated February 27, 2026. Accessed March 30, 2026. https://clinicaltrials.gov/study/NCT04526106