HER2-mutant non-small cell lung cancer (NSCLC) is a rare subtype with a high incidence of brain metastases and few targeted options. At the IASLC 2025 World Conference on Lung Cancer, phase 1 Beamion LUNG-1 data of the HER2-selective TKI zongertinib (Hernexeos) in advanced/metastatic HER2-mutant NSCLC were presented, and in August 2025, the FDA granted accelerated approval for previously treated patients in this population. The trial used dose escalation (all HER2-altered solid tumors) followed by NSCLC-only dose expansion across five cohorts, including groups with treated, stable brain metastases and patients who were treatment-naive with active brain metastases.
Safety in these brain-metastases cohorts was consistent with prior reports. Intracranially, 41% of patients achieved an objective response by Response Assessment in Neuro-Oncology Brain Metastases, the disease control rate was 83%, and median progression-free survival was 8.2 months. Investigators emphasized the significance of brain activity with zongertinib, noting limited prior evidence of intracranial efficacy for HER2 TKIs in this setting. Next steps include the phase 3 Beamion LUNG-2 trial comparing first-line zongertinib vs standard chemotherapy to clarify sequencing; longer follow-up will further define durability of intracranial responses. Taken together, these signals—along with previously reported systemic activity—suggest zongertinib may offer a promising targeted option for patients with HER2-mutant NSCLC, including those with brain metastases.
Reference: Eleazar A, Ruiter G. Beamion LUNG-1 Study: Zongertinib’s Novel Brain Activity in HER2-Mutant NSCLC. Targeted Oncology. Published October 1, 2025. Accessed October 16, 2025. https://www.targetedonc.com/view/beamion-lung-1-study-zongertinib-s-novel-brain-activity-in-her2-mutant-nsclc
