The FDA has approved lirafugratinib (Lyrfigtu) for adults with previously treated, unresectable or metastatic cholangiocarcinoma harboring FGFR2 gene fusions or rearrangements, based on the REFOCUS phase 1/2 trial. The study included 116 patients and met its primary efficacy endpoints using RECIST v1.1, reporting a 46% objective response rate (ORR) and median duration of response (DOR) of 11.8 months. In parallel trial reporting, median progression-free survival was 11.3 months, with nearly half of patients progression-free at one year. The FDA decision also comes with safety label warnings characteristic of FGFR inhibition, including ocular toxicity, hyperphosphatemia and embryo-fetal toxicity. For biotech and pharma teams focused on molecularly defined oncology, the approval underscores regulators’ continued reliance on biomarker-selected cohorts and durable response metrics in small, single-group trials for hard-to-treat cancers.