This is an investigator-initiated, single arm, open label phase 1b/2 study to identify the recommended phase 2 dose (RP2D), safety, tolerability, and preliminary efficacy of the combination of osimertinib, necitumumab, and trastuzumab (ONT) in adults with histologically confirmed, metastatic NSCLC with an activating and sensitizing EGFR mutation....Pts treated at DL 1 and DL 2 had no dose-limiting toxicities (DLTs) and 1/6 pts at DL 3 had a DLT (persistent grade 3 rash). Due to grade 2 and 3 rash and paronychiae occurring after cycle 1 at DL 3, DL2 was determined to be the RP2D.The proportion of evaluable phase 1b pts achieving partial response or stable disease was 58.3% (7/12)....ONT toxicities are manageable, and the combination has promising preliminary efficacy in refractory EGFR-mutated metastatic NSCLC.