In summary, the combination of APG-2449 and EGFR TKIs synergistically enhances antitumor activity in EGFR-mutant NSCLC models, with synergy driven by downregulation of FAK, EGFR, SRC, and ERK phosphorylation and APG-2449 extending the duration of response to osimertinib. Here, EGFR is linked to non-small cell lung carcinoma.