A phase II open-label study (FIGHT-202) evaluated pemigatinib in patients with previously treated, advanced or metastatic cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements. The study enrolled 147 patients across three cohorts based on FGFR2 status. Pemigatinib, a selective FGFR1-3 inhibitor, was administered at 13.5 mg/day. The primary endpoint was objective response rate (ORR) in cohort A (FGFR2 fusions/rearrangements), with a secondary endpoint of progression-free survival (PFS) and overall survival (OS). The study showed a 37% ORR in cohort A, with a median duration of response (DOR) of 9.1 months and median PFS of 7.0 months and OS of 17.5 months. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia, alopecia, and diarrhea. Pemigatinib was generally well-tolerated, with manageable side effects. The study demonstrated durable responses and prolonged OS in patients with FGFR2 alterations. The results support the use of pemigatinib in patients with FGFR2-altered CCA. The study highlights the importance of molecular profiling in identifying patients who may benefit from targeted therapy. The findings suggest that FGFR inhibitors, such as pemigatinib, represent a promising treatment option for patients with FGFR2-altered CCA. The study also underscores the need for further research into the role of FGFR inhibitors in biomarker-selected CCA.A phase II open-label study (FIGHT-202) evaluated pemigatinib in patients with previously treated, advanced or metastatic cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements. The study enrolled 147 patients across three cohorts based on FGFR2 status. Pemigatinib, a selective FGFR1-3 inhibitor, was administered at 13.5 mg/day. The primary endpoint was objective response rate (ORR) in cohort A (FGFR2 fusions/rearrangements), with a secondary endpoint of progression-free survival (PFS) and overall survival (OS). The study showed a 37% ORR in cohort A, with a median duration of response (DOR) of 9.1 months and median PFS of 7.0 months and OS of 17.5 months. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia, alopecia, and diarrhea. Pemigatinib was generally well-tolerated, with manageable side effects. The study demonstrated durable responses and prolonged OS in patients with FGFR2 alterations. The results support the use of pemigatinib in patients with FGFR2-altered CCA. The study highlights the importance of molecular profiling in identifying patients who may benefit from targeted therapy. The findings suggest that FGFR inhibitors, such as pemigatinib, represent a promising treatment option for patients with FGFR2-altered CCA. The study also underscores the need for further research into the role of FGFR inhibitors in biomarker-selected CCA.