Boehringer Ingelheim’s HERNEXEOS® (zongertinib tablets) has received accelerated approval from the U.S. Food and Drug Administration (FDA) as the first orally administered targeted therapy for adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain activating mutations, detected by an FDA-approved test, who have received prior systemic therapy. This approval, granted under the FDA’s Accelerated Approval Program following Priority Review and Breakthrough Therapy Designation, is based on data from the Phase Ib Beamion-LUNG 1 trial, which demonstrated a 75% objective response rate (N=71), with 6% complete responses, 69% partial responses, and a duration of response of ≥6 months in 58% of patients. Results were presented at the 2025 AACR Annual Meeting and published in The New England Journal of Medicine. Continued approval may depend on confirmatory trials verifying clinical benefit.
HER2 mutations, present in 2–4% of NSCLC cases, are linked to poor prognosis and increased brain metastases risk. Zongertinib, a tyrosine kinase inhibitor, selectively targets HER2, addressing uncontrolled cell proliferation and tumor growth. Comprehensive biomarker testing via next-generation sequencing is essential to identify eligible patients. The treatment’s safety profile is manageable, with a 2.9% discontinuation rate and common adverse reactions including diarrhea (53%), hepatotoxicity (27%), rash (27%), fatigue (22%), and nausea (21%).
Lung cancer, particularly NSCLC, is the leading cause of cancer-related deaths globally, with over 3 million cases projected by 2040. Most NSCLC patients are diagnosed at advanced stages (III or IV), with a historical 5-year survival rate below 10% for metastatic disease, significantly impacting quality of life. Zongertinib’s approval marks a significant advancement for patients with limited options, offering a targeted approach to a subgroup with HER2-mutant NSCLC. Advocacy groups emphasize the importance of biomarker testing to access such personalized therapies. Boehringer Ingelheim’s rapid development of zongertinib, completed within four years, underscores its commitment to innovative cancer care, with ongoing trials evaluating the drug across other HER2-altered solid tumors.
