Fig. 4: Patient-derived models of FGFR2 fusion-positive ICC are sensitive to FGFR inhibition.

A GI₅₀ assay with pemigatinib in the PDC-DUC18828 model confirmed the IC₅₀ value to be 4 nM, determined by Alamarblue after 3 days treatment. B PDC-DUC18828 relative viability is impaired by pemigatinib in a dose-dependent manner. Triplicate results are averaged and normalized to DMSO control (0 nM pemigatinib) in this 7 day assay, determined by Cell TiterGlo. C Clonogenic assay demonstrating dose-dependent loss of viability in PDC-DUC18828 but not in two FGFR2 wildtype cell lines, RBE and SSP-25. D GI₅₀ assay with pemigatinib in the PDO-DUC18828 model confirmed the IC₅₀ value to be 2 nM. Viability results are normalized to DMSO control and presented as the mean +/− standard deviation (error bars) for three biologically independent replicates. E Pemigatinib impairs tumor growth in vivo. Mice bearing subcutaneous xenografts (~125 mm³) were randomized to control (sham gavage with Ora-plus suspension) vs pemigatinib (5 mg/kg oral gavage) and were treated 5 days per week. Tumor volume was measured 3×/week until study endpoints were reached. Compared to control, pemigatinib significantly impaired tumor growth, evidenced by the prolonged time to tumor volume endpoint (p < 0.05 beginning on day 14 of treatment, indicated by the asterisk (*); data represented as mean +/− standard error of the mean for each experimental condition, consisting of 8 mice each and compared using the Student’s t test). F Median overall survival of mice treated with pemigatinib (from Fig. 4E), determined by Kaplan–Meier method, is 53 days, compared to 32 days for mice treated with sham gavage (p < 0.0001). All in vitro (A, B, D) results are normalized to DMSO control and presented as the mean +/− standard deviation (error bars) for three biologically independent replicates.