FDA approves HERNEXEOS as first targeted therapy for HER2‑mutant advanced NSCLC

The U.S. FDA granted accelerated approval to HERNEXEOS (zongertinib) as a first‑line targeted treatment for adults with HER2‑mutant advanced non‑small cell lung cancer, based on a 76% objective response rate in a 72‑patient cohort. A Phase III confirmatory trial (Beamion LUNG‑2) is enrolling to verify clinical benefit.

The U.S. Food and Drug Administration approved HERNEXEOS (zongertinib tablets) for adults with advanced non‑small cell lung cancer that has HER2 tyrosine kinase domain activating mutations. The approval is an accelerated approval based on measures of objective response and duration of response. Boehringer Ingelheim previously received accelerated approval for the drug in previously treated patients and was granted Breakthrough Therapy designation for first‑line use. A Phase III confirmatory trial is underway to further evaluate the medicine. Key findings: - The accelerated approval is based on a Phase Ib Beamion LUNG‑1 cohort of 72 treatment‑naïve patients that showed a 76% objective response rate, including 11% complete responses and 65% partial responses. - Duration of response was reported as at least 6 months in 64% of those patients. - In a pooled safety population of 292 patients (treatment‑naïve and previously treated), adverse events led to dose discontinuation in 6%; the most common adverse reactions (>20%) included diarrhea (54%), rash (28%), hepatotoxicity (27%), fatigue (25%), nausea (23%), musculoskeletal pain (21%), and upper respiratory tract infection (20%). - The FDA awarded Breakthrough Therapy designation for first‑line use and a Commissioner's National Priority Voucher for zongertinib. - Boehringer Ingelheim is enrolling patients in Beamion LUNG‑2, a Phase III confirmatory trial of zongertinib as a first‑line treatment, and is also conducting Beamion LUNG‑3 in early‑stage disease. Summary: The approval establishes HERNEXEOS as an FDA‑authorized oral targeted therapy for adults with HER2‑mutant advanced NSCLC under accelerated approval, based on objective response and duration measures from early‑phase data. Continued approval may be contingent on verification of clinical benefit in the ongoing Phase III confirmatory trial (Beamion LUNG‑2). Further study results and regulatory review will inform the drug's long‑term status for this indication.