Zongertinib Earns FDA Accelerated Approval in HER2+ NSCLC

The FDA also approved the Oncomine Dx Target Test to help identify those with HER2 TKD activating mutations in patients who may be eligible to receive zongertinib.

The FDA granted accelerated approval to the kinase inhibitor zongertinib (Hernexeos) as a treatment for adult patients with previously treated metastatic or unresectable nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) activating mutations as detected with an FDA-approved test, according to a news release from the agency.1

The regulatory agency also approved the Oncomine Dx Target Test as a companion diagnostic for identifying HER2 TKD activating mutations in those who may be eligible to undergo treatment with zongertinib.

Supporting data for the accelerated approval came from the phase 1b Beamion LUNG-1 trial (NCT04886804), which assessed zongertinib in 71 patients who received prior platinum-containing chemotherapy but no anti-HER2 tyrosine kinase inhibitors or antibody drug conjugates (ADCs). Among these patients, the objective response rate (ORR) was 75% (95% CI, 63%-83%), with 58% achieving a response lasting for at least 6 months.

Among 34 patients who received prior platinum-based chemotherapy plus a HER2-directed ADC, the ORR was 44% (95% CI, 29%-61%). Furthermore, 27% of those with a response in this cohort achieved a response for at least 6 months.

The prescribing information for zongertinib includes warnings and precautions for hepatotoxicity, interstitial lung disease, left ventricular dysfunction, and embryo-fetal toxicity.

The FDA approved zongertinib at a recommended dose that is dependent on patient body weight. Patients weighing less than 90 kg are recommended to receive zongertinib at 120 mg orally once daily. Additionally, those of 90 kg or higher should receive the agent at 180 mg orally once daily. The agency recommends administering the agent with or without food until progressive disease or unacceptable toxicity.

The Beamion LUNG-1 trial's primary end points were ORR and DOR based on blinded independent central review using RECIST v1.1 criteria.

Previously, the FDA granted priority review to zongertinib as a treatment for this NSCLC population in February 2025.2

References

1. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. FDA. August 8, 2025. Accessed August 8, 2025. https://tinyurl.com/bdh2d4uc
2. Boehringer’s zongertinib receives priority review from U.S. FDA for the treatment of HER2 (ERBB2)-mutant advanced non-small cell lung cancer. News release. Boehringer Ingelheim. February 19, 2025. Accessed August 8, 2025. https://tinyurl.com/4475t495