Zongertinib (Hernexeos®) — FDA Approval Summary
1. Approved Indication & Date
On August 8, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zongertinib for the treatment of adults with unresectable or metastatic nonsquamous non‑small cell lung cancer (NSCLC) whose tumors harbor HER2 tyrosine kinase domain (TKD) activating mutations, and who have received prior systemic therapy .
2. Regulatory Designations
The application benefited from multiple expedited FDA review pathways: Priority Review Breakthrough Therapy designation Fast Track designation .
3. Clinical Trial Evidence
Approval was based on results from the Beamion LUNG‑1 (NCT04886804) open-label, multicenter trial . Key findings include: Patients with prior platinum-based chemotherapy only (n=71): Objective Response Rate (ORR): 75% (95% CI: 63–83%) Duration of Response (DOR ≥ 6 months): 58% Patients previously treated with chemotherapy and a HER2-targeted antibody–drug conjugate (n=34): ORR: 44% (95% CI: 29–61%) DOR ≥ 6 months: 27%
4. Dosing & Companion Diagnostic
Dosing: For patients < 90 kg: 120 mg orally once daily For patients ≥ 90 kg: 180 mg orally once daily Can be taken with or without food, continued until disease progression or unacceptable toxicity . A companion diagnostic, the Oncomine™ Dx Target Test, was also approved to detect HER2 TKD activating variants and identify eligible patients .
5. Safety & Warnings
The prescribing information includes important warnings and precautions for: Hepatotoxicity Left ventricular dysfunction Interstitial lung disease / pneumonitis Embryo‑fetal toxicity .
Summary table:
Approval Date
August 8, 2025
Indication
Metastatic/unresectable NSCLC with HER2 TKD mutations
Expedited Pathways
Priority Review, Breakthrough Therapy, Fast Track
Efficacy (ORR)
75% in prior-chemo only; 44% in chemo + HER2‑ADC cohort
Dosing
120 mg (< 90 kg); 180 mg (≥ 90 kg); oral once daily
Companion Test
Oncomine™ Dx Target Test
Safety Concerns
Liver, lung, heart toxicity; fetal harm warnings