Elevar Therapeutics doses first patients in FGFR2 Phase 2 expansion

Elevar Therapeutics has dosed the first patients in ReFocus202, a global Phase 2 study evaluating lirafugratinib in solid tumours harbouring FGFR2 fusions or rearrangements beyond cholangiocarcinoma. The first patient was treated at Samsung Medical Center in Seoul, South Korea; a second followed at Moffitt Cancer Center in Tampa, Florida. The multi-site, open-label, single-arm study spans sites across the United States, South Korea, the United Kingdom, Spain, and France.

The primary endpoint is objective response rate. Elevar intends to conduct an interim analysis once at least seven tumour types have been enrolled with a minimum of five patients per type, leveraging both ReFocus202 data and an existing dataset of 42 non-CCA patients across 13 tumour types from its earlier Phase 1/2 ReFocus study, which already demonstrated what the company describes as meaningful antitumour activity.

Scientific rationale and regulatory context

Lirafugratinib is an oral, selective small-molecule inhibitor of FGFR2, a receptor tyrosine kinase implicated in a range of solid tumours. The compound showed FGFR2-dependent activity in preclinical models and demonstrated activity against known on-target resistance mutations in vitro and in vivo, a property that matters clinically as acquired resistance to FGFR inhibitors has been a recurring limitation in the class.

The drug already holds FDA Orphan Drug and Fast Track designations for cholangiocarcinoma, and a new drug application in previously treated CCA patients with FGFR2 fusion or rearrangement is under FDA priority review, with a PDUFA date set for 27 September 2026. Approval in CCA would give Elevar a commercial anchor from which to prosecute the broader tumour-agnostic strategy underpinning ReFocus202.

Richard Kim, principal investigator and service chief of medical gastrointestinal oncology at Moffitt Cancer Center, said: "This study gives us an important opportunity to better understand whether selective FGFR2 inhibition with lirafugratinib can benefit a broader group of patients whose tumours are driven by FGFR2 alterations."

Competitive landscape

The tumour-agnostic FGFR2 inhibitor space has attracted meaningful competitive interest. Infigratinib and futibatinib have both received FDA approval in FGFR2-positive CCA, while pemigatinib holds approvals in CCA and certain myeloid malignancies. The differentiation Elevar is pursuing centres on selectivity: pan-FGFR inhibitors carry off-target toxicities, including hyperphosphataemia and ocular side effects, that a more selective FGFR2 compound could in principle reduce, improving tolerability and potentially widening the eligible patient population.

A tumour-agnostic label, if supported by the ReFocus202 data, would align lirafugratinib with the broader regulatory trend toward basket-trial approvals based on biomarker rather than histology. The FDA's experience with approvals for other tumour-agnostic agents, including larotrectinib for NTRK fusions and selpercatinib for RET alterations, provides a regulatory read-across that could support this pathway. However, the bar for a single-arm tumour-agnostic application remains high, and Elevar will need robust, consistent response rates across multiple tumour types to build a compelling dossier.

Elevar is a majority-owned subsidiary of South Korea's HLB Group and is headquartered in Fort Lee, New Jersey. No enrolment timeline or target patient number for ReFocus202 was disclosed in the announcement.