FDA Approves Zongertinib for Non-Squamous Non-Small Cell Lung Cancer With HER2 Tyrosine Kinase Domain Activating Mutations

On August 8, 2025, the US Food and Drug Administration (FDA) approved zongertinib (Hernexeos; Boehringer Ingelheim Pharmaceuticals) for previously treated patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test. 

In this multicenter, open-label study, 105 patients who received systemic platinum-based chemotherapy either with (n = 34) or without (n = 71) a HER2-targeted tyrosine kinase inhibitor or antibody drug conjugate received zongertinib, based on body weight, until disease progression or unacceptable toxicity. Primary end points included objective response rate (ORR) and duration of response, as assessed via blinded independent central review. 

At analysis, among patients who received platinum-based chemotherapy, the ORR was 75% and 58% of patients had a duration of response lasting ≥6 months. Among patients who received platinum-based chemotherapy plus a HER2-targeted tyrosine kinase inhibitor or antibody drug conjugate, the ORR was 44% and 27% of patients had a duration of response lasting ≥6 months. 

The FDA has also approved the Oncomine Dx Target Test to aid in the detection of HER2 tyrosine kinase domain activating mutations among patients with non-squamous NSCLC who may be eligible for zongertinib treatment. 

The recommended dose of once daily zongertinib is 120 mg for patients weighing <90 kg and 180 mg for patients weighing ≥90 kg, taken with or without food until disease progression or unacceptable toxicity.  Prescribing information includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease, pneumonitis, and embryo-fetal toxicity.  

Source:

FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. Published on August 8, 2025. Accessed on August 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations