Lytgobi (futibatinib)

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.

P1, N=18, Not yet recruiting, Northwestern University

Despite additive anti-tumor activity for FGFR and MEK inhibition in KRASmt NSCLC lines, the trial was stopped after dose escalation, as no RP2D was identified for futibatinib/binimetinib due to reversible retinopathies. Trial register number. NCT04965818. Trial registration date. 20-September-2021.

P3, N=603, Completed, Institut National de la Santé Et de la Recherche Médicale, France | Active, not recruiting --> Completed

A comprehensive literature search was performed in PubMed/MEDLINE, Embase, and Scopus for studies published from January 2000 to February 2026, using combinations of the terms 'cholangiocarcinoma,' 'FGFR2,' 'fibroblast growth factor receptor,' and 'futibatinib.' Relevant clinical trials, translational studies, and review articles were screened for inclusion. Futibatinib represents the most biologically rational FGFR inhibitor currently available for FGFR2-altered CCA, as it directly addresses the dominant mechanism limiting the efficacy of earlier agent, on-target resistance driven by secondary FGFR2 kinase domain mutations.

P2/3, N=15, Enrolling by invitation, Taiho Oncology, Inc. | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Dec 2026 --> Apr 2027

The incidence of FGFRi-associated nail toxicities varies by agent and can affect quality of life and treatment adherence. The pathogenesis remains unclear, and no predictive biomarkers exist. Further research into optimized management and preventative strategies is needed. Early recognition and proactive multidisciplinary management are essential to minimizing complications and maintaining oncologic treatment continuity. &nbsp.

Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.

In addition, partial regression of FGFR1N546K mutant tumor lesions occurred upon treatment with the FGFR inhibitor futibatinib and low-intensity chemotherapy in a patient with refractory neuroblastoma. Together, our data demonstrate that FGFR1N546K is a strong oncogenic driver in neuroblastoma that is associated with failure of current standard chemotherapy, and suggest potential clinical benefit of FGFR-directed therapies in FGFR1 mutant high-risk patients.

The complementary activity of lirafugratinib and futibatinib against FGFR2 kinase domain mutations supports their sequential use, when precise resistance mutations are detected in patients.

P1, N=85, Active, not recruiting, Boundless Bio | Recruiting --> Active, not recruiting | N=127 --> 85