Efficacy and safety of lirafugratinib in FGFRi -naïve cholangiocarcinoma (CCA) patients harboring FGFR2 fusions/rearrangements ( FGFR2 f/r).

作者：Antoine Hollebecque, Mitesh J. Borad, Peter Lu, Xianzhang Meng, Kristin Ryan, Laura M. Alexander, Jia Liu, Do-Youn Oh, Richard D. Kim · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.2_suppl.476 · 被引用次数：3 · 研究领域：Fibroblast Growth Factor Research、Cholangiocarcinoma and Gallbladder Cancer Studies、IgG4-Related and Inflammatory Diseases

476 Background: Outcomes remain poor for patients with advanced/metastatic CCA treated with first-line gemcitabine-cisplatin +/- anti-PD(L)1. Lirafugratinib is the first highly selective, irreversible FGFR2 inhibitor designed to target oncogenic FGFR2 driver alterations and resistance mutations. ReFocus (NCT04526106) is an open-label, multicenter phase 1/2 study in patients with advanced/metastatic CCA and other solid tumors with FGFRok2 alterations. Methods: Pivotal cohort of patients (n=116) with advanced/metastatic CCA harboring FGFR2 f/r previously treated with ≥1 systemic therapy and FGFR i-naive were treated with oral lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST v1.1 by independent review committee (IRC). Key secondary endpoint was duration of response (DOR); other secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and quality of life per EORTC QLC-C30. Results: As of 27SEP2024, the primary efficacy analysis of IRC-assessed data (n=114) and the secondary analysis of investigator-assessed data (n=116) set was done. The primary efficacy analysis excluded 2 patients as not available. Median age 57 years with 61.4% female. IRC-assessed ORR was 47%, and median DOR was 11.8 months (mos) (95% CI, 7.5-13.0), where 76.2% of responses lasted >6 mos. Median PFS was 11.3 mos (95% CI, 9.2, 14.8), with 12-month rate of 49.2%. Median...