On February 26, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zongertinib (Hernexeos), a kinase inhibitor, for an expanded indication for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.
Zongertinib had previously received accelerated approval in August 2025 for adults with nonsquamous NSCLC with these mutations who had received prior systemic therapy. Today's accelerated approval extends this treatment options to patients who have not received prior therapy.
This application is part of the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.
Beamion LUNG-1
Efficacy was evaluated in Beamion LUNG-1 (ClinicalTrials.gov identifier NCT04886804), a single arm, open-label, multicenter, multicohort trial. The efficacy population included 72 patients with unresectable or metastatic nonsquamous NSCLC with HER2 TKD mutations who had not received systemic therapy for advanced disease.
The major efficacy outcome measures were objective response rate and duration of response determined by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Objective response rate was 76% (95% confidence interval [CI] = 65%–85%), with 64% of responders having a duration of response of ≥ 6 months and 44% having a duration of response of ≥ 12 months.
The prescribing information for zongertinib 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 less than 90 kg, the dose is 120 mg orally once daily. For patients weighing 90 kg or more, the dose is 180 mg orally once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.
Expedited Programs
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review. Zongertinib received Breakthrough Therapy designation.
