Lung cancer remains the leading cause of cancer death around the world, with the global incidence estimated to exceed 3 million cases by 2040. Non-small cell lung cancer (NSCLC) is the most common subtype, and most patients present with stage III or IV disease due to infrequent symptoms and misdiagnosis of lung cancer. At this stage of the disease, the cancer has typically progressed locally with metastasis to distant organs. The five-year survival rate for metastatic NSCLC remains below 10%. Thus, patients living with advanced NSCLC often are faced with significant physical, psychological, and emotional burdens.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to HERNEXEOS® (zongertinib tablets), an oral tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2). It received approval as a targeted treatment for adults with unresectable or metastatic (NSCLC) harboring HER2 tyrosine kinase domain activating mutations confirmed by an FDA-approved test, and who have previously received systemic therapy. The approval was granted by the FDA under the FDA’s Accelerated Approval Program under Priority Review, Breakthrough Therapy, and Fast Track Designations.
Marcia Horn, President and CEO of the International Cancer Advocacy Network and Executive Director of the Exon 20 Group/HER2 Warriors, emphasized that this approval underscores the urgent need for personalized treatment strategies in lung cancer. “For patients with NSCLC, it is essential to have a full understanding of their cancer’s unique biomarkers (HER2 is one of them) through extensive testing, as it opens up targeted treatment options.”
The approval is based on objective response rate (ORR) and duration of response (DOR) data, with continuation of approval reliant on confirmatory trials validating clinical benefit. “Zongertinib provides an effective, targeted, oral medication for HER2-mutant NSCLC with a durable response and good safety profile,” stated Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center and lead coordinating investigator for the Beamion-LUNG 1 trial. “This is an important advancement for a patient population with limited therapeutic options.”
The Phase Ib Beamion-LUNG 1 trial served as the basis for approval. In total, 71 patients were treated with zongertinib, achieving a 75% ORR, with 6% and 69% being complete response (CR) and partial response (PR), respectively. Among the 53 patients (58%), the DOR was at least six months. These findings were shared at the 2025 American Association for Cancer Research (AACR) Annual Meeting and published in The New England Journal of Medicine.
This treatment had an acceptable safety profile, with only 2.9% of patients discontinuing treatment (i.e., study drug) due to adverse events. Nausea (21%), fatigue (22%), rash (27%), hepatotoxicity (27%), and diarrhea (53%) were the most frequently observed adverse reactions (>20%) in the pooled safety population.
“We are delighted to introduce HERNEXEOS, which may redefine the standard of care for HER2-mutant advanced NSCLC, a disease with a poor prognosis,” Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim, explained. “We believe in the power of scientific innovation, and we were able to accelerate development and deliver this treatment approach within four years of starting the first clinical trial.
References: Tereza Urbankova. U.S. FDA grants accelerated approval to Boehringer’s HERNEXEOS® as first orally administered targeted therapy for previously treated patients with HER2-mutant advanced NSCLC. Published August 8, 2025. Accessed August 12, 2025. FDA approval of HERNEXEOS® first oral treatment HER2-mutant advanced NSCLC | Boehringer Ingelheim
