The use of tyrosine kinase inhibitors (TKIs) in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has not produced the same durable clinical benefits observed with next-generation targeted therapies in ALK- and ROS1-rearranged NSCLC. Given the molecular heterogeneity of EGFR-mutant NSCLC, which includes over 100 distinct mutations, there is a continued need for more effective and mutation-specific therapeutic strategies.