Lirafugratinib (Lyrfigtu) has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a category 2A preferred subsequent-line therapy for disease progression in cholangiocarcinoma (CCA) harboring an FGFR2 fusion or other rearrangement.¹ The update follows the FDA’s September 23, 2026, approval of the oral FGFR2 inhibitor for adults with previously treated, unresectable, locally advanced or metastatic disease.²

Elevar Therapeutics, a majority-owned subsidiary of HLB Co, Ltd, announced the guideline addition on November 3, 2026. The company expects lirafugratinib to be available to patients in the US in the fourth quarter of 2026.¹ The agent is a selective, irreversible, covalent-binding inhibitor of FGFR2 designed to limit activity against other members of the FGFR family.^2,3

FDA Approval and REFOCUS Data

The approval was based on the phase 1/2 REFOCUS trial (NCT04526106), a multicenter, open-label, single-arm study that included 116 patients with unresectable or metastatic CCA who had not received an FGFR inhibitor and had previously received chemotherapy or chemoimmunotherapy.^2,4 Patients received lirafugratinib at 70 mg orally once daily until disease progression or unacceptable toxicity.

Per independent review committee assessment using RECIST v1.1, the confirmed objective response rate (ORR) was 46% (95% CI, 36%-55%), and the median duration of response was 11.8 months (95% CI, 7.5-13.0).² Because REFOCUS had no comparator arm, the data do not allow direct efficacy comparisons with other FGFR inhibitors.

An earlier analysis of the FGFR inhibitor–naive, chemotherapy-exposed cohort (n = 114) was presented at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. It reported a confirmed ORR of 46.5% (95% CI, 37.1%-56.1%), a disease control rate of 96.5%, a median progression-free survival of 11.3 months (95% CI, 9.2-14.8), and a median overall survival of 22.8 months (95% CI, 18.1-27.2).³

Safety Profile

The most common any-grade treatment-related adverse events in that analysis were nail toxicities (87.9%), palmar-plantar erythrodysesthesia (81.9%), stomatitis (78.4%), and retinal pigment epithelial detachment (37.1%). Grade 3 or higher rates for these events were 12.1%, 32.8%, 12.1%, and 1.7%, respectively. Treatment-related adverse events led to treatment discontinuation in 4.3% of patients.³

The FDA’s warnings and precautions for lirafugratinib include ocular toxicity, hyperphosphatemia with soft tissue mineralization, and embryo-fetal toxicity.² Elevar has characterized the safety profile as predictable and manageable through dose adjustments.¹

Treatment Landscape in FGFR2-Altered CCA

Gemcitabine/cisplatin combined with an immune checkpoint inhibitor remains the standard first-line treatment for advanced biliary tract cancer. For patients with FGFR2-altered CCA who progress, the FGFR inhibitors pemigatinib (Pemazyre) and futibatinib (Lytgobi) were already approved in the previously treated setting, and no randomized data directly comparing them with lirafugratinib are available.

For context, the FDA granted lirafugratinib breakthrough therapy designation and orphan drug designation, and the application received priority review. It was evaluated under the Real-Time Oncology Review pilot program.²

“The NCCN Guidelines are an important tool in helping clinicians determine the optimal treatment options for their patients. We are pleased that lirafugratinib was promptly added to the guidelines upon FDA approval,” said Rose Lai, MD, senior vice president of clinical development, Elevar Therapeutics, in a news release.¹

Ongoing Development

Elevar is also evaluating lirafugratinib in a clinical trial enrolling additional patients with previously treated, advanced or metastatic solid tumors other than CCA that harbor an FGFR2 fusion or rearrangement and have not been treated with a prior FGFR inhibitor. The company holds an exclusive license to the agent from Relay Therapeutics, Inc.

FAQs

What did the NCCN change for FGFR2-altered cholangiocarcinoma?

The NCCN Guidelines added lirafugratinib as a category 2A preferred subsequent-line therapy for disease progression in CCA with an FGFR2 fusion or other rearrangement. Elevar Therapeutics announced the addition on November 3, 2026.

What is lirafugratinib?

Lirafugratinib (Lyrfigtu) is an oral, selective, irreversible, covalent-binding inhibitor of FGFR2. It is designed to limit activity against other FGFR family members.

Who is the FDA-approved indication for?

Adults with previously treated, unresectable, locally advanced or metastatic CCA harboring an FGFR2 gene fusion or other rearrangement. The recommended dose is 70 mg orally once daily until disease progression or unacceptable toxicity.

What data support the approval?

The approval was based on REFOCUS, a multicenter, open-label, single-arm trial of 116 patients who had not received an FGFR inhibitor and had previously received chemotherapy or chemoimmunotherapy. Per independent review committee assessment, the confirmed objective response rate was 46% (95% CI, 36%-55%), and the median duration of response was 11.8 months (95% CI, 7.5-13.0).

What are the main safety considerations?

The FDA’s warnings and precautions include ocular toxicity, hyperphosphatemia with soft tissue mineralization, and embryo-fetal toxicity. In an earlier REFOCUS analysis, the most common any-grade treatment-related adverse events were nail toxicities (87.9%), palmar-plantar erythrodysesthesia (81.9%), stomatitis (78.4%), and retinal pigment epithelial detachment (37.1%). Treatment-related adverse events led to discontinuation in 4.3% of patients.

How does lirafugratinib compare with other FGFR inhibitors?

Pemigatinib (Pemazyre) and futibatinib (Lytgobi) were already approved for previously treated FGFR2-altered CCA. REFOCUS had no comparator arm, and no randomized data directly comparing lirafugratinib with either agent are available.

When will lirafugratinib be available?

Elevar expects it to be available to patients in the US in the fourth quarter of 2026.

Is lirafugratinib being studied in other cancers?

Yes. Elevar is evaluating it in a clinical trial of previously treated, advanced or metastatic solid tumors other than CCA that harbor an FGFR2 fusion or rearrangement and have not been treated with a prior FGFR inhibitor.

REFERENCES

1. Elevar Therapeutics announces lirafugratinib (Lyrfigtu) added to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as second-line therapy for cholangiocarcinoma with FGFR2 fusion or other rearrangement. News release. Elevar Therapeutics. November 3, 2026. Accessed November 4, 2026. https://tinyurl.com/jt2fv5k9

2. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. News release. US FDA. September 23, 2026. Accessed November 4, 2026. https://tinyurl.com/2nw4n4mu

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

4. A first-in-human study of highly selective FGFR2 inhibitor, RLY-4008, in patients with intrahepatic cholangiocarcinoma (ICC) and other advanced solid tumors. ClinicalTrials.gov. Updated February 27, 2026. Accessed November 4, 2026. https://clinicaltrials.gov/study/NCT04526106