VJToday

FDA grants accelerated approval to zongertinib for HER2-mutant non-small cell lung cancer

On February 26, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zongertinib, a kinase inhibitor, for unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC).1 Despite advances in molecularly targeted therapy for common oncogenic drivers like EGFR and ALK in lung cancer, a subset of NSCLC defined by activating HER2 (ERBB2) mutations has historically lacked effective precision treatments. Until recently, HER2-mutant disease was managed with standard chemotherapy and, in some cases, antibody–drug conjugates, but durable responses and meaningful survival extensions have been elusive, highlighting a clear unmet need for therapies tailored to this molecular subtype.2

Efficacy for zongertinib was assessed in the multi-cohort, open-label Beamion LUNG-1 trial (NCT04886804), which enrolled patients with advanced NSCLC and confirmed HER2 TKD mutations. Among patients who had not received systemic therapy for advanced disease, objective response rate (ORR) reached 76% (95% CI, 65–85), with 64% of responders maintaining response for at least six months and 44% sustaining response for a year or longer. The safety profile of zongertinib additionally reflects known class effects.1

Sanjay Popat, MBBS, FRCP, PhD, Royal Marsden Hospital, London, UK, commented:

“This is an important group of patients because they have no targeted therapies approved for use and the standard of care is currently chemotherapy with or without immunotherapy. A total of 74 patients were enrolled in the study and the primary endpoint was ORR, a confirmed objective response rate, and indeed the primary endpoint was met.”

This accelerated approval marks an important step in precision oncology for HER2-mutant NSCLC, offering clinicians an oral, targeted option that delivers meaningful response rates and durable benefit in a setting with limited alternatives.

References:

  1. Center for Drug Evaluation and Research. FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer [Internet]. U.S. Food and Drug Administration. 2026 [cited 2026 Feb 26]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell
  2. Uy NF, Merkhofer CM, Baik CS. HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies. Cancers. 2022 Aug 27;14(17):4155.