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.

Early termination limited the ability to draw definitive conclusions on the efficacy of infigratinib as first-line treatment of FGFR2-rearranged CCA. This study illustrates the challenges of powering confirmatory studies in biomarker-selected subpopulations of rare tumors and highlights the need for regulatory collaboration to develop pragmatic frameworks for assessing novel therapies in ultra-rare malignancies.

P3, N=114, Completed, QED Therapeutics, a BridgeBio company | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Dec 2025

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

Its efficacy was intermediate between methotrexate and the selective NTRK2 inhibitor ana-12. Mechanistically, Lucitanib targeted the NTRK2-AKT-MMP9 axis while preserving immune effector functions. These findings establish NTRK2 as a viable therapeutic target in gliomas and highlight Lucitanib as a novel multi-mechanistic inhibitor with balanced efficacy and favorable pharmacokinetic properties, supporting its further development for clinical translation in NTRK2-overexpressing gliomas.

Importantly, pharmacological inhibition of FGFR1 using BGJ398 synergized with anti-PD-1 therapy, resulting in enhanced antitumor efficacy in preclinical models...Collectively, these findings identify FGFR1 as a key mediator of ICB resistance in HCC. Targeting FGFR1 represents a promising strategy to reprogram the immunosuppressive TME and enhance response to immunotherapy, with potential additional value as a predictive biomarker.

Outside allogeneic stem cell transplantation (ASCT), survival with conventional therapy is dismal, representing an unmet clinical need. We summarize here the data that led to approval of pemigatinib, a FGFR1 inhibitor, showing unprecedented efficacy in M/LN-FGFR1.

P2, N=63, Completed, Eisai Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Nov 2025 | Trial primary completion date: Mar 2026 --> Nov 2025

P=N/A, N=60, Recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2030 --> Nov 2032 | Trial primary completion date: Nov 2030 --> Nov 2032

P2, N=24, Not yet recruiting, Dana-Farber Cancer Institute

P1, N=51, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P1, N=5, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Sep 2027 --> Aug 2026 | Trial primary completion date: Oct 2026 --> Mar 2025