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.
