The U.S. Food and Drug Administration (FDA) has granted accelerated approval to HERNEXEOS® (zongertinib tablets) for the treatment of adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, after prior systemic therapy. Approval is based on objective response rate (ORR) and duration of response (DoR), with continued approval contingent on confirmatory trial results.
Data from the Phase Ib Beamion-LUNG 1 trial showed a 75% ORR (6% complete, 69% partial responses) in 71 patients, with 58% achieving a DoR of at least six months. The most common adverse events (>20%) included diarrhea, hepatotoxicity, rash, fatigue, and nausea. Discontinuation due to side effects occurred in 2.9% of patients. Results were presented at AACR 2025 and published in The New England Journal of Medicine.
HER2 mutations occur in 2–4% of NSCLC cases, often linked to poor prognosis and higher brain metastasis risk. Comprehensive biomarker testing using next-generation sequencing is essential to identify eligible patients.
“With zongertinib, we have a durable, targeted, oral treatment for HER2-mutant NSCLC in the U.S., where current options are limited,” said Dr. John Heymach of MD Anderson Cancer Center.
Shashank Deshpande, Chairman of Boehringer Ingelheim’s Board of Managing Directors, emphasized the company’s accelerated development timeline, bringing HERNEXEOS to patients within four years of its first trial.
Patient advocate Marcia Horn highlighted the importance of biomarker testing: “Knowing your cancer’s HER2 status can unlock targeted treatments that make a real difference.”