New York, United States | August 14, 2025- The Food and Drug Administration granted accelerated approval to zongertinib (Hernexeos, Boehringer Ingelheim Pharmaceuticals, Inc.), a kinase inhibitor, for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.
FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for treatment with zongertinib.
Approval was based on data from the Phase Ib Beamion LUNG-1 trial (NCT04886804). Among patients who had received prior platinum-based chemotherapy but were treatment-naïve to HER2-targeted drugs, zongertinib demonstrated a 75% overall response rate (ORR), with 58% of responses lasting six months or more.
In a second cohort previously treated with both platinum chemo and HER2-directed therapies, the ORR was 44%, with 27% of patients maintaining responses for at least six months. Median progression-free survival (PFS) was reported at 12.4 months, with a median duration of response (DOR) of 14.1 months.
The recommended zongertinib dose is based on body weight. For patients weighing < 90 kg, the dose is 120 mg orally once daily. For patients weighing ≥ 90 kg, the dose is 180 mg orally once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.
HER2 mutations account for 2–4% of NSCLC cases and are associated with aggressive disease and limited treatment options. Experts say this approval emphasizes the need for comprehensive biomarker testing, including next-generation sequencing, to guide personalized treatment decisions.
As part of the accelerated approval pathway, continued approval of zongertinib depends on confirmatory data from the ongoing Phase III Beamion LUNG-2 trial (NCT06151574). This study is evaluating the drug’s efficacy against standard-of-care treatments in a similar patient population.
