Based on promising pre-clinical data, which demonstrated antitumor activity of HER3-DXd in multiple solid tumor xenograft models61, a phase I study was initiated in patients with locally advanced or metastatic EGFR-driven NSCLC with prior treatment with EGFR TKI and platinum-based chemotherapy (NCT03260491), which ultimately led to FDA breakthrough therapy designation (BTD) in December 2021. This evidence concerns the gene ERBB3 and non-small cell lung carcinoma.