Phase IB Study of Osimertinib in Combination with Navitoclax in -mutant NSCLC Following Resistance to Initial Therapy (ETCTN 9903).

Purpose: Osimertinib is an effective therapy in -mutant non-small cell lung cancer (NSCLC), but resistance invariably develops. Navitoclax is an oral inhibitor of BCL-2/BCL-xL that has exhibited synergy with osimertinib in preclinical models of -mutant NSCLC. In hematologic malignancies, BCL-2 family inhibitors in combination therapy effectively increase cellular apoptosis and decrease drug resistance.