Multinational phase 2 trial of pemigatinib for previously treated solid tumors with activating FGFR1-FGFR3 alterations

Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. The multinational phase 2 FIGHT-207 trial evaluated the oral FGFR1-FGFR3 inhibitor pemigatinib for FGFR-altered advanced solid tumors. Patients were included in cohorts A (fusions/rearrangements), B (activating non-kinase domain mutations), and C (kinase domain mutations, potentially pathogenic variants of unknown significance). The ORRs to pemigatinib in cohorts A, B, and C were 26.5%, 9.4%, and 3.8%. In cohorts A and B, the median progression-free survival was 4.5 and 3.7 months, the median duration of response was 7.8 and 6.9 months, and the median overall survival was 17.5 and 11.4 months, respectively. There were no new safety signals. The most common any-grade treatment-emergent adverse events were hyperphosphatemia (84%) and stomatitis (53%). TP53 co-mutations were associated with lack of response and BAP1 alterations with higher response rates. FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance. The authors conclude that pemigatinib demonstrated activity in patients with previously treated solid tumors with activating FGFR1-FGFR3 alterations.