Based on the strong antitumor activity of M4205 in GIST xenograft models with primary oncogenic KIT mutations in exon 11 (this study) and exon 9 (50), which was superior compared with the current first-line treatment imatinib, it is tempting to speculate whether M4205 could even be considered as a first-line therapy option given the significantly lower risk for the occurrence of on-target resistance mutations. The gene discussed is KIT; the disease is gastrointestinal stromal tumor.