Zongertinib in Treatment-Naïve Patients With HER2-mutant NSCLC, Including Those With Active Brain Metastases: Beamion LUNG-1

HER2 mutations occur in 2% to 4% of non–small cell lung cancers (NSCLCs) and are associated with aggressive disease and a high incidence of brain metastases. Zongertinib is an oral, irreversible tyrosine kinase inhibitor that selectively targets HER2 while sparing wild-type EGFR. In this OncLive Rapid Readout, Ticiana Leal, MD, discusses data from the phase 1a/1b BeamionLUNG-1 study evaluating frontline zongertinib in treatment-naive patients with HER2-mutant advanced NSCLC, including those with active brain metastases, presented at the 2026 European Lung Cancer Congress in Copenhagen, Denmark. In the treatment-naive cohort (n = 74), zongertinib demonstrated an overall response rate of 76%, a median progression-free survival of 14.4 months, and a median duration of response of 15.2 months. Intracranial responses were also observed in patients with active brain metastases. The safety profile was manageable, with low rates of grade 3 or higher treatment-related adverse events. These data supported the FDA accelerated approval of zongertinib in the frontline setting in February 2026.