FDA officials have granted accelerated approval to zongertinib (Hernexeos), a kinase inhibitor, for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD)-activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.1
The FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to aid in detecting HER2 TKD-activating mutations in patients with nonsquamous NSCLC who may be eligible for treatment with zongertinib.
Efficacy was evaluated in patients with unresectable or metastatic, nonsquamous NSCLC with HER2 TKD mutations who had received prior systemic therapy and received zongertinib in Beamion LUNG-1 (NCT04886804), an open-label, multicenter, multicohort trial. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) determined by blinded independent central review per RECIST v1.1.
Among 71 patients who received prior platinum-based chemotherapy but had not been previously treated with a HER2-targeted tyrosine kinase inhibitor or antibody–drug conjugate (ADC), ORR was 75% (95% confidence interval [CI], 63-83), with 58% having a DOR ≥6 months.
Among 34 patients previously treated with platinum-based chemotherapy and an HER2-targeted ADC, ORR was 44% (95% CI, 29-61), with 27% having a DOR ≥6 months.
The prescribing information includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.
The recommended zongertinib dose is based on body weight. For patients weighing <90 kg, the dose is 120 mg orally once daily. For patients weighing ≥90 kg, the dose is 180 mg orally once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.
Reference
- US Food and Drug Administration. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. August 8, 2025. Accessed August 14, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations