FDA Grants Accelerated Approval to Zongertinib for HER2-Mutated NSCLC
In a major step forward for lung cancer treatment, the U.S. Food and Drug Administration (FDA) has granted accelerated approval to zongertinib (Hernexeos, Boehringer Ingelheim Pharmaceuticals, Inc.). This marks the first oral targeted therapy for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) that involves HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations. Eligible patients must have received prior systemic therapy and have confirmed HER2 TKD mutations using an FDA-approved test.
Alongside this approval, the FDA also cleared the Oncomine Dx Target Test by Life Technologies Corporation. This companion diagnostic helps detect HER2 TKD mutations and identifies patients who may benefit from zongertinib.
The FDA’s decision relies on findings from the ongoing Phase Ib Beamion LUNG-1 trial (NCT04886804). Among patients previously treated with platinum-based chemotherapy but not HER2-directed therapies, zongertinib produced an overall response rate (ORR) of 75%. Of those who responded, 58% maintained their response for at least six months.
In another group—those who had received both platinum chemotherapy and HER2-targeted treatments—the ORR was 44%. Among them, 27% sustained their response for six months or longer. The trial also reported a median progression-free survival (PFS) of 12.4 months and a median duration of response (DOR) of 14.1 months.
Zongertinib dosing is based on patient weight. Patients weighing under 90 kg take 120 mg orally once daily. Those 90 kg or more take 180 mg once daily. The drug can be taken with or without food and should be continued until disease progression or intolerable side effects occur.
HER2 mutations occur in about 2–4% of NSCLC cases. These mutations are often linked to more aggressive tumors and have historically offered limited treatment options. Experts stress the importance of comprehensive genomic profiling, including next-generation sequencing (NGS), in guiding personalized treatment decisions.
Because the FDA granted zongertinib accelerated approval, its continued availability depends on results from the ongoing Phase III Beamion LUNG-2 trial (NCT06151574). This study is comparing zongertinib to standard treatment options in a similar group of patients to confirm its clinical benefit.
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