IACS-13909 is a specific and potent allosteric inhibitor of SHP2 that suppresses the signaling of RTK/MAPK pathway and overcomes multiple mechanisms underlying osimertinib resistance. IACS-13909 potently impedes the proliferation of tumors with a broad spectrum of RTKs as the oncogenic driver. Importantly, in NSCLC models with acquired resistance to osimertinib, IACS-13909 administered as a single agent or in combination with osimertinib potently reduces tumor cell proliferation in vitro and in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFR inhibitor-resistant NSCLC.
