Fig. 1

Combination of pan-HER and c-Met inhibitors effectively block the HER-family and the c-Met receptor coactivated functions. Data for an example patient, C135, demonstrates the efficacy of combining neratinib and tepotinib against abnormal stimulation response generated by simultaneous application of the three growth factors (GF)—NRG, EGF, and HGF. Each curve is labeled in the figure to indicate the inhibitor(s) that was added to different wells containing the same number of cells. The order of efficacy response compared to the growth factor only well (at the top of the graph) from low response to high is as follows—Tepotinib alone is least efficacious, Neratinib alone is more efficacious, and the most efficacious treatment is the combination of neratinib and tepotinib data curve that in the figure is just above the dotted blue baseline for untreated cells (no agonist, no antagonist control)