To assess the functional role of high FGFR1 expression in KRASG12C-mutant cancer cells, pemigatinib, a potent and selective inhibitor of FGFR1-3, was tested alone or in combination with KRASG12C inhibitors. The combination of pemigatinib and KRASG12C inhibitors was synergistic in mesenchymal-like lung cancer cells with high FGFR1 expression, whereas no synergy was observed in cells with low FGFR1 expression....We demonstrate that NSCLC with a mesenchymal-like phenotype and harboring high FGFR1 expression and KRASG12C mutations may uniquely benefit from combination treatment.