The FDA has granted accelerated approval to zongertinib (Hernexeos) for adult patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain mutations who have received prior systemic therapy. This decision was supported by findings from the phase 1 Beamion LUNG-1 trial, where zongertinib monotherapy was assessed in patients with advanced NSCLC harboring HER2 alterations. Patients pretreated with platinum-based chemotherapy and no prior HER2-targeted tyrosine kinase inhibitor or antibody drug conjugate (ADC) achieved a 75% overall response rate (ORR). Those who had also received HER2-targeted ADCs achieved a 44% ORR. The six-month duration of response rates were 58% and 27% in these groups, respectively, highlighting durable benefit for many patients.
The Beamion LUNG-1 study also showed a favorable safety profile, with most treatment-related adverse effects being mild, particularly diarrhea and rash. Only one patient experienced a grade 3 or higher adverse event, and treatment discontinuations were rare. Zongertinib is being further evaluated in the phase 3 Beamion LUNG-2 trial, which will compare the drug to standard-of-care therapy for HER2-mutant NSCLC. These findings underscore zongertinib’s potential as a new targeted option for patients with HER2-mutant NSCLC, filling an important gap in treatment where options remain limited.
Reference: Ryan C. FDA Grants Accelerated Approval to Zongertinib for Nonsquamous NSCLC With HER2 TKD Mutations. OncLive. Published August 8, 2025. Accessed August 19, 2025. https://www.onclive.com/view/fda-grants-accelerated-approval-to-zongertinib-for-nonsquamous-nsclc-with-her2-tkd-mutations
