FDA Receives NDA for Lirafugratinib in 2L FGR2-Mutated Cholangiocarcinoma

Lirafugratinib was the subject of a new drug application (NDA) submitted to the FDA for the second-line treatment of adult patients with cholangiocarcinoma (CCA), or bile duct cancer, harboring FGFR2 fusions or rearrangements, according to a press release from the developer, Elevar Therapeutics.¹ The submission seeks to establish the highly selective FGFR2 inhibitor as a precision therapy for patients whose disease has progressed following at least 1 prior line of systemic therapy.

Findings from the pivotal phase 1/2 ReFocus trial (NCT04526106) demonstrated significant antitumor activity with lirafugratinib in patients with FGFR2 fusion-positive CCA. Results were recently shared at the 2025 ASCO Gastrointestinal Cancers Symposium.²

“We are excited to work with the FDA as it reviews the submission while simultaneously preparing for a potential commercial launch,” stated Dong-Gun Kim, the chief executive officer of Elevar Therpauetics, in the press release.¹

Clinical Efficacy

In an efficacy analysis conducted by an independent review committee (IRC) on a pivotal cohort of 114 evaluable patients who were fibroblast growth factor receptor inhibitor (FGFRi)–naïve but had received prior chemotherapy, lirafugratinib achieved a confirmed objective response rate (ORR) of 46.5% (95% CI, 37.1%-56.1%). This included a complete response rate of 2.6% and a partial response rate of 43.9%.

The agent also demonstrated a high disease control rate (DCR) of 96.5% (95% CI, 91.3%-99.0%), with 50.0% of patients achieving stable disease. Responses were characterized by their durability, with a median duration of response (DOR) of 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) reached 22.8 months (95% CI, 18.1-27.2). Subgroup analyses also indicated robust activity in chemotherapy-naïve patients (n = 11), where the ORR was 63.6% (95% CI, 30.8%-89.1%).

ReFocus Trial Design

The open-label, multi-center ReFocus trial evaluated the safety and efficacy of lirafugratinib across various solid tumors with FGFR2 alterations.³ For the pivotal CCA cohort, patients received a standardized dose of 70 mg administered orally once daily.

Eligibility criteria required participants to have histologically or cytologically confirmed locally advanced or metastatic CCA that was refractory to standard therapy, have not adequately responded to standard therapy, have no available standard or curative therapy, or be intolerant to/have declined standard therapy. Patients also must have had an ECOG performance status of 0 or 1.

The study’s primary endpoint was confirmed ORR per RECIST v1.1. Secondary endpoints included DCR, DOR, PFS, OS, and safety.

Safety Results

The safety profile of lirafugratinib in the pivotal cohort (n = 116) was consistent with its design as a highly selective inhibitor. Common any-grade treatment-related adverse events (TRAEs) included nail toxicities (87.9%), palmar-plantar erythrodysesthesia (PPE) syndrome (81.9%), and stomatitis (78.4%). Grade 3 or higher TRAEs were reported in 57.8% of patients, with the most frequent being PPE (32.8%) and stomatitis (12.1%).

Notably, no TRAEs led to death, and the treatment discontinuation rate due to toxicities was 4.3%. TRAEs led to dose reduction and dose interruption in 75.9% and 82.8% of patients, respectively.

In the presentation on the ReFocus data, the lead study author Antoine Hollebecque, MD, stated, “Lirafugratinib at the proposed dose regimen of 70 mg [once daily] demonstrated positive antitumor activity in patients with previously treated, unresectable, locally advanced or metastatic [CCA] harboring FGFR2 fusions or rearrangements.” Hollebecque, MD, is the lead study author of ReFocus, as well as the senior medical oncologist at the Gustave Roussy Cancer Institute.

References

1. Elevar seeks FDA approval for FGFR2 inhibitor in bile duct cancer. News release. Elevar Therapeutics. Published January 20, 2026. Accessed January 30, 2026. https://tinyurl.com/yhx9ty9v
2. 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