We investigated the effect of combined APG-2449 and EGFR TKIs in mice bearing xenografts derived from (1) NSCLC HCC827 with EGFREx19del (SCID-beige mice); (2) NCI-H1975 with EGFRL858R_T790M mutation (BALB/c nude mice); and (3) a PDX model with EGFRL858R_T790M and ROS1 fusion (LD1–0006-215,676; NU/NU mice). Here, ROS1 is linked to non-small cell lung carcinoma.