FDA Grants Priority Review to Lirafugratinib in FGFR2+ Cholangiocarcinoma

The FDA has accepted and granted priority review to a new drug application (NDA) for lirafugratinib as a treatment for patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements, according to a press release from the developer, Elevar Therapeutics.¹

A Prescription Drug User Fee Act (PDUFA) target action date of September 27, 2026, has been set. The NDA, which was submitted in January 2026, is based on findings from the pivotal phase 1/2 ReFocus trial (NCT04526106), which evaluated the safety and efficacy of the highly selective, irreversible FGFR2 inhibitor in patients with FGFR2-altered solid tumors.²

ASCO GI ReFocus Results

In January 2026, clinical efficacy data supporting the application were presented at the 2026 ASCO Gastrointestinal Cancers Symposium.³ In the cohort of patients with FGFR2 fusion– or rearrangement–positive cholangiocarcinoma who were FGFR inhibitor–naive and had previously received chemotherapy, lirafugratinib elicited a confirmed objective response rate (ORR) of 46.5% (95% CI, 37.1%-56.1%) as assessed by an independent review committee (IRC). The disease control rate (DCR) was 96.5% (95% CI, 91.3%-99.0%), and the median duration of response (DOR) reached 11.8 months (95% CI, 7.5-13.0). Furthermore, the median progression-free survival (PFS) was 11.3 months (95% CI, 9.2-14.8), and the median overall survival (OS) was 22.8 months (95% CI, 18.1-27.2).

“Lirafugratinib has established a compelling clinical profile that differentiates it from existing treatment options,” stated Dong-Gun Kim, chief executive officer of Elevar, in the press 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 Design

ReFocus is an open-label, multicenter, first-in-human study designed with 4 distinct parts: dose escalation, dose expansion, extension, and a rollover portion. In the dose-escalation portion, 58 and 41 patients, respectively, with solid tumors were enrolled to continuous and discontinuous dosing schedules, and 17 patients received treatment every other day. Notably, patients with cholangiocarcinoma were assigned to receive oral lirafugratinib at a recommended phase 2 dose of 70 mg.

All patients enrolled had received prior chemotherapy and 36.8% received prior immune checkpoint inhibition.

To meet eligibility criteria, patients were required to be 18 years or older with histologically or cytologically confirmed advanced solid tumors harboring FGFR2 gene fusions, mutations, or amplifications that was refractory to or had relapsed on standard therapy. Participants also needed an ECOG performance status of 0 or 1 and measurable disease per RECIST v1.1 criteria. The primary end point was IRC-assessed ORR, with secondary end points including DOR, DCR, PFS, OS, and safety.

Safety findings indicated that the most common treatment-related adverse events (TRAEs) were consistent with known class effects of FGFR2 inhibition. Grade 3 or higher TRAEs occurred in 57.8% of patients in the FGFR-naïve but chemotherapy pretreated population, with the most frequent toxicities including palmar-plantar erythrodysesthesia (32.8%), stomatitis (12.1%), and nail toxicities (12.1%). Investigators noted that the safety profile was manageable through dose modifications, and only 4.3% of patients discontinued treatment due to adverse events.

Lirafugratinib is designed to selectively target FGFR2 alterations while minimizing off-target inhibition of other FGFR isoforms, which may reduce the incidence of certain toxicities like hyperphosphatemia. If approved, the agent would offer a targeted second-line option for a patient population that historically faces poor outcomes following progression on standard platinum-based chemotherapy.

References

1. Elevar Therapeutics announces FDA acceptance for review of new drug application for lirafugratinib as second-line cholangiocarcinomatTreatment. News release. Elevar Therapeutics. March 30, 2026. Accessed March 31, 2026. https://tinyurl.com/4a3cu27c
2. Elevar seeks FDA approval for FGFR2 inhibitor in bile duct cancer. News release. Elevar Therapeutics. Published January 20, 2026. Accessed March 31, 2026. https://tinyurl.com/yhx9ty9v
3. Hollebecque A, Borad MJ, Lu P, et al. Efficacy and safety of lirafugratinib in FGFRi-naïve 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