Lyrfigtu (lirafugratinib) — oral pill for previously treated FGFR2-altered bile duct cancer

Lyrfigtu is an oral kinase inhibitor of FGFR2 (lirafugratinib; also studied as RLY-4008). On 23 September 2026, the U.S. Food and Drug Administration approved Lyrfigtu for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma (bile duct cancer) harboring an FGFR2 gene fusion or other rearrangement. Applicant named on the FDA oncology notice: Elevar Therapeutics, Inc. Elevar materials state an exclusive worldwide commercial license from Relay Therapeutics, Inc. Full Prescribing Information was expected to post on Drugs@FDA after the notice; use the current carton USPI with the clinic when it is available.

Distinct path — not this carton (fact-only): Other FGFR inhibitors already have (or had) US labelled CCA doors — for example Pemazyre (pemigatinib) and Lytgobi (futibatinib). Truseltiq (infigratinib) had a prior accelerated CCA label that was later withdrawn. Those are separate molecules, doses, and labels. A non-CCA solid-tumor research programme for lirafugratinib (for example ReFocus202 — NCT07359820 on secondary sources) is not the US commercial CCA indication. Today’s US labelled once-daily oral Lyrfigtu door for previously treated FGFR2 fusion/rearrangement cholangiocarcinoma is Elevar Lyrfigtu.

Where this is taking place

Commercial labelled door today: United States — FDA-approved Lyrfigtu for the adult CCA population above. This is a GI / hepatobiliary / medical oncology conversation: confirm FGFR2 fusion or other rearrangement on appropriate molecular testing, confirm prior systemic treatment and unresectable / advanced disease, plan once-daily oral dosing, and arrange eye exams / phosphate monitoring as the clinician directs from the Prescribing Information. Company materials describe expected U.S. availability by Q4 2026 — launch timing is company; a labelled indication is not the same sentence as every pharmacy stocking tomorrow. Prior authorisation and specialty-pharmacy logistics still apply. This is not a DIY import.

Outside the United States: As of this draft, Health Canada, European Commission, MHRA, TGA, PMDA/MHLW, and Swissmedic authorisation for Lyrfigtu / lirafugratinib are not confirmed. Elevar company materials describe a marketing authorisation application submitted to the EMA (announced 15 September 2026) for a similar second-line FGFR2 fusion/rearrangement CCA use — submission / review ≠ a European Commission marketing authorisation. Do not import on your own. A US bottle is not a foreign carton.

REFOCUS — NCT04526106 — Phase 1/2, multicenter, open-label, first-in-human study of RLY-4008 / lirafugratinib in unresectable or metastatic CCA and other FGFR2-altered solid tumors (dose escalation, expansion, extension, rollover). Lead sponsor on ClinicalTrials.gov: Elevar Therapeutics. CT.gov status retrieved for this draft: COMPLETED (start 2 Sep 2020; primary / study completion 5 Sep 2025). Actual enrolment on the record: 490. FDA efficacy population for the CCA label: 116 adults with unresectable or metastatic cholangiocarcinoma who were naïve to FGFR inhibitor treatment and had received prior chemotherapy or chemoimmunotherapy. Honesty: A completed pivotal evidence programme supports the label — that is not open new enrolment into REFOCUS, and international trial sites are not a foreign marketing authorisation.

The practical door in the US is an oncology clinician who can confirm the molecular result, prior-line history, baseline eye and laboratory monitoring, and write labelled 70 mg once daily — not treating NCT04526106 as walk-in recruitment.

Approval matrix

Access by country

• United States: Ask a GI / hepatobiliary / medical oncology clinician about FDA-labelled Lyrfigtu. Labelled 23 September 2026 for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement. Recommended dose on the FDA oncology notice: 70 mg orally once daily until disease progression or unacceptable toxicity. Path: confirm histology and FGFR2 fusion/rearrangement → confirm prior systemic therapy and advanced / unresectable disease → baseline monitoring (including eyes and phosphate as the PI directs) → specialty pharmacy / payer steps. Suspected adverse reactions: FDA MedWatch 1-800-FDA-1088 / www.fda.gov/medwatch. No list price or copay dollars in this article. This is US commercial labelled supply, not a DIY import.

• Canada: Lyrfigtu authorisation not confirmed. Ask the Canadian hepatobiliary / GI oncology clinic what legal paths exist in Canada when a Canadian Product Monograph is not confirmed. Do not treat a US bottle as a Canadian care plan.

• European Union: Company materials describe an EMA MAA for lirafugratinib in advanced / metastatic FGFR2 fusion or rearrangement CCA — that is a filing, not an EC marketing authorisation. Ask the local oncology centre for current EU status. Do not import on your own.

• United Kingdom / Australia / Japan / other countries: Regulator authorisation not confirmed in this draft. Trial geography is not a commercial foreign carton.

• If your regulator has not authorised it: do not import on your own. Ask the local clinician about documented special-access / named-patient rules, referral to a centre in a labelled country, or waiting — without treating a US bottle as a foreign carton.

Who is eligible

This is an adult, previously treated, FGFR2 fusion/rearrangement CCA conversation on the FDA oncology approval notice — not a front-line labelled indication and not a paediatric CCA label on sources used here.

United States (FDA oncology notice, 23 September 2026):

• Indication: Treatment of adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement.
• Evidence population framing: REFOCUS enrolled 116 patients with unresectable or metastatic CCA who were FGFR-inhibitor naïve and had received prior chemotherapy or chemoimmunotherapy.
• Recommended dosage (FDA notice): 70 mg orally once daily until disease progression or unacceptable toxicity.
• Molecular testing: The labelled population requires an FGFR2 gene fusion or other rearrangement. A named FDA-approved companion diagnostic for Lyrfigtu was not confirmed on the oncology notice retrieved for this draft — ask the oncology team which validated assay they use and how results map to this indication.
• Warnings and precautions named on the FDA notice: ocular toxicity; hyperphosphatemia and soft tissue mineralization; embryo-fetal toxicity.
• Pediatrics: Not established for this indication on sources used here (adult indication text).

Not labelled on sources confirmed for this draft:

• Front-line / chemotherapy-naïve commercial use as the US labelled sentence (the labelled indication is previously treated).
• CCA without an FGFR2 fusion or other rearrangement.
• Using Lyrfigtu as a free swap for pemigatinib, futibatinib, or another FGFR inhibitor without a clinician reading each label.
• Health Canada, EC, MHRA, TGA, PMDA/MHLW, or Swissmedic marketing authorisations (not confirmed here).
• Treating COMPLETED REFOCUS or non-CCA expansion research as the commercial CCA prescription desk.

What the pivotal study showed (REFOCUS / FDA oncology notice)

Use the FDA oncology notice (and the current USPI when posted) for a US prescription conversation. Conference abstracts and company materials are supportive reading and are labeled when used below.

REFOCUS — NCT04526106 (FDA efficacy population):

• Multicenter, open-label, single-arm evaluation in 116 adults with unresectable or metastatic cholangiocarcinoma who were naïve to FGFR inhibitor treatment and had received prior chemotherapy or chemoimmunotherapy.
• Patients received lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity.
• Major efficacy outcome measures: objective response rate (ORR) and duration of response (DOR) by independent review committee per RECIST v1.1.
• ORR: 46% (95% CI: 36, 55).
• Median DOR: 11.8 months (95% CI: 7.5, 13.0).

Company / conference numbers (not a substitute for the FDA notice): Elevar and ASCO GI 2026 materials (Hollebecque et al., Abstract 476) have also reported disease-control and survival figures for FGFR-inhibitor–naïve, previously treated FGFR2 fusion/rearrangement CCA cohorts (for example disease control rate and median PFS / OS on those materials). Treat those as company / conference figures until they appear on the USPI; the FDA notice anchors ORR and DOR for this draft.

Trial-status honesty: REFOCUS is COMPLETED on ClinicalTrials.gov. That supports the labelled evidence package — it is not a new-enrolment commercial door.

How it is taken

From the FDA oncology notice (confirm against the posted Prescribing Information with the clinic):

Food rules, tablet strengths, missed-dose instructions, dose modifications for toxicity, and drug–drug interaction tables were not in the FDA oncology notice retrieved for this draft — ask the prescribing clinician for the current USPI once Drugs@FDA posts it.

Safety (what the label puts first)

The FDA oncology notice states that the prescribing information includes warnings and precautions for:

• Ocular toxicity
• Hyperphosphatemia and soft tissue mineralization
• Embryo-fetal toxicity

Report suspected adverse reactions through the clinic and FDA MedWatch (1-800-FDA-1088).

Company-reported safety colour (company — not the FDA notice table): Elevar materials and secondary clinical reports describe lower rates of some class-typical events on lirafugratinib relative to pan-FGFR inhibitors (for example company-cited hyperphosphatemia and diarrhea percentages) and list common adverse reactions across broader treated populations. Those figures are company / secondary; they do not replace the posted USPI adverse-reaction tables. Ask the oncology team for the carton Medication Guide / USPI when available.

How to talk to a doctor

Bring (or ask the clinic to pull):

1. Pathology confirming cholangiocarcinoma and whether disease is unresectable, locally advanced, or metastatic.
2. Molecular report showing an FGFR2 fusion or other rearrangement (assay name, specimen type, date).
3. Prior systemic therapy list (chemotherapy, chemoimmunotherapy, prior FGFR inhibitor if any) and dates of progression.
4. Eye history and any recent ophthalmology notes (ocular toxicity is on the FDA warning list).
5. Current medicines and supplements (phosphate binders, other oral cancer drugs, contraception plans if pregnancy is possible).
6. A direct question: “Given my FGFR2 result and prior treatment, does labelled Lyrfigtu fit, and what monitoring (eyes, phosphate, labs) would you schedule if we start 70 mg daily?”
7. If you are outside the United States: “Has our regulator authorised Lyrfigtu, or what legal paths exist here — without me importing a US bottle?”

This is information for a clinic conversation — not medical advice.

Research and regulatory team (from sources only — no invented contacts)

• Applicant / commercial sponsor on FDA notice: Elevar Therapeutics, Inc.
• Originator / license (company): exclusive worldwide license from Relay Therapeutics, Inc. (Elevar materials).
• Pivotal programme: REFOCUS (NCT04526106); ClinicalTrials.gov lead sponsor Elevar Therapeutics.
• Conference reporting: Hollebecque A, Borad MJ, Lu P, et al. — ASCO Gastrointestinal Cancers Symposium 2026, Abstract 476 (secondary clinical reporting of REFOCUS CCA efficacy).
• Ex-US regulatory path (company): EMA MAA submission announced 15 September 2026 — not an EC decision.

Canada zoom: authorisation not confirmed

Lyrfigtu / lirafugratinib authorisation is not confirmed on Health Canada sources used for this draft. A US FDA approval and a completed international trial are not a Canadian Product Monograph. Ask a Canadian GI / hepatobiliary oncology clinic what legal options exist in Canada. Do not mail-order a US bottle as a Canadian care plan.

EU zoom: MAA submitted — not authorised

Elevar company materials announce an EMA marketing authorisation application for lirafugratinib in advanced / metastatic FGFR2 fusion or rearrangement CCA (15 September 2026 company notice). Filing starts review. It is not a European Commission marketing authorisation. Until an EC decision and SmPC exist, do not treat Lyrfigtu as EU-labelled supply. Do not import on your own.

Bottom line

Lyrfigtu (lirafugratinib) is an FDA-approved once-daily oral option (70 mg) for adults in the United States with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma that harbors an FGFR2 gene fusion or other rearrangement. The labelled evidence package rests on REFOCUS (NCT04526106) — ORR 46%, median DOR 11.8 months on the FDA oncology notice. Eye toxicity, phosphate / soft-tissue mineralization, and embryo-fetal risk are named watchpoints. Other FGFR inhibitor cartons are not this bottle. Outside the US, authorisation is not confirmed; an EMA filing is not an EU licence. Authorized is not funded. Talk with a GI / hepatobiliary oncology clinician about testing and whether labelled US Lyrfigtu fits — and do not import on your own.

Primary sources

• FDA oncology approval notice — lirafugratinib / Lyrfigtu (23 September 2026): https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lirafugratinib-previously-treated-unresectable-locally-advanced-or-metastatic
• ClinicalTrials.gov — REFOCUS (NCT04526106): https://clinicaltrials.gov/study/NCT04526106
• Elevar Therapeutics company FDA-approval announcement (company, 23 September 2026): https://www.globenewswire.com/news-release/2026/09/23/3367897/0/en/elevar-therapeutics-announces-fda-approval-of-lyrfigtu-lirafugratinib-as-second-line-cholangiocarcinoma-with-fgfr2-fusion-or-other-rearrangement-treatment-option.html
• Elevar Therapeutics company EMA MAA announcement (company, 15 September 2026): https://www.globenewswire.com/news-release/2026/09/15/3362487/0/en/elevar-therapeutics-submits-marketing-authorization-application-to-european-medicines-agency-for-lirafugratinib-as-a-treatment-for-patients-with-advanced-metastatic-cholangiocarcin.html

When Drugs@FDA posts the Lyrfigtu Prescribing Information and approval letter, prefer those PDFs over secondary rewrite for dose-modification, AE tables, and NDA number.