FDA Authorizes Accelerated Approval to Zongertinib and Diagnostic Device for HER2-Mutated NSCLC

On August 8, the FDA granted accelerated approval to zongertinib, a kinase inhibitor for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations and have received prior systemic therapy, as well as the Oncomine Dx Target Test as a companion diagnostic device.

This decision is based on results from Beamion LUNG-1 (NCT04886804), an open-label, multi-center, multi-cohort trial. Among the trial’s 71 participants who had previously received platinum-based chemotherapy but no HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate (ADC), the objective response rate (ORR) was 75%, with a duration of response (DOR) of 58%. In patients who had been treated with both platinum-based chemotherapy and a HER2-targeted ADC, the ORR was 44% and the DOR was 27%.

According to an FDA press release, the recommended zongertinib dose is based on body weight, with 120 mg orally once daily recommended for those weighing < 90 kg and 180 mg orally once daily recommended for those weighing 90 kg or more. Potential adverse events include hepatotoxicity, left ventricular dysfunction, interstitial lung disease, and embryo-fetal toxicity.

The regulatory assessment and data review for this application was streamlined through the Rel-Time Oncology Review pilot program the Assessment Aid.

Reference:
FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations. Published August 8, 2025. Accessed August 13, 2025.