The U.S. Food and Drug Administration (FDA) has granted accelerated approval for zongertinib (Hernexeos) a new targeted therapy for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations. The expanded accelerated approval includes first line use as well as for patients whose cancers have progressed after prior systemic therapy.
Zongertinib is designed for patients whose HER2 TKD mutations are detected by an FDA-approved test. To facilitate this, the FDA also approved the Oncomine Dx Target Test as a companion diagnostic to identify eligible patients.
Key Results from Clinical Trials
- Individuals treated with prior platinum-based chemotherapy (but not HER2-targeted TKI or antibody-drug conjugate):
- Objective Response Rate (ORR): 75% (95% CI: 63, 83)
- Duration of Response (DOR ≥ 6 months): 58%
- Individuals previously treated with platinum-based chemotherapy and a HER2-targeted ADC:
- ORR: 44% (95% CI: 29, 61)
- DOR ≥ 6 months: 27%
These results were observed in the Beamion LUNG-1 trial (NCT04886804), a global, open-label, multi-center study.
Updated results from Beamion LUNG-1 included 72 people with advanced non‑small cell lung cancer (NSCLC) that could not be removed with surgery, and whose tumors had a specific change in the HER2 (ERBB2) gene, received this medicine as their first treatment for advanced disease. Doctors looked at how many patients’ tumors shrank (the “response rate”) and how long those responses lasted. In this study, about 3 out of 4 patients (76%) had their tumors shrink. Among those who responded, about 2 out of 3 had their response last at least 6 months, and nearly half had their response last at least 12 months.
Safety warnings include:
- Hepatotoxicity
- Left ventricular dysfunction
- Interstitial lung disease/pneumonitis
- Embryo-fetal toxicity
This development marks a promising advance in lung cancer therapy for patients with rare HER2 mutations, offering a treatment tailored to their specific genetic profile. Cancer patients and providers may consult their healthcare teams about eligibility and monitoring as more information becomes available.
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