Zongertinib: First Approval

DeclarationsFunding The preparation of this review was not supported by any external funding.Authorship and Conflict of interest Arnold Lee is a contracted employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability not applicableAdditional information about this Adis Drug Review can be found hereAbstractZongertinib (HERNEXEOS®) is a small molecule, irreversible, HER2-specific tyrosine kinase inhibitor being developed by Boehringer Ingelheim for the treatment of advanced solid tumours with HER2 aberrations. Zongertinib selectively inhibits HER2-expressing cells, including those with HER2 mutations, while sparing cells expressing wild-type EGFR. It received its first approval under accelerated approval in August 2025 in the USA following positive results from the Beamion LUNG-1 phase Ia/Ib trial in patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This article summarizes the milestones in the development of zongertinib leading to this first approval for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.© Springer Nature Switzerland AG 2026