FDA Approves Zongertinib for HER2-Mutated Metastatic NSCLC

Key Clinical Summary:

• The FDA has approved zongertinib for patients with HER2-mutated, unresectable or metastatic, non-squamous non-small cell lung cancer based on results from the phase 2 Beamion LUNG-1 trial, a single-arm, open-label, multicenter study of 72 treatment-naïve patients.
• The objective response rate was 76% by blinded independent review. Among responders, 64% had responses lasting ≥6 months and 44% had responses lasting ≥12 months, demonstrating clinically meaningful durability.
• Zongertinib provides a highly active, oral, first-line option for HER2-mutant NSCLC, a biomarker-defined population with limited targeted therapies. Accelerated approval underscores the importance of routine HER2 mutation testing and supports continued evaluation to confirm long-term benefit.

On February 26, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to zongertinib, a kinase inhibitor, for adult patients with HER2-mutated, unresectable or metastatic, non-squamous non-small cell lung cancer (NSCLC), as detected by an FDA-approved test. This approval was based on results from the Beamion LUNG-1 trial.

In this open-label, single-arm trial, 72 patients who had not received prior systemic therapy for advanced disease received zongertinib once daily until disease progression or unacceptable toxicity. Primary end points included objective response rate (ORR) and duration of response, as assessed by blinded independent central review.

At analysis, the ORR was 76%. Among responders, 64% had a duration of response of ≥6 months and 44% had a duration of response of ≥12 months.

The recommended once-daily dose of zongertinib is 120 mg for patients weighing <90 kg and 180 mg for patients weighing ≥90 kg. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.

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

Source:

US Food and Drug Administration. FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer. Accessed February 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell