HER2 Inhibitor Approved for Certain Newly Diagnosed, HER2-mutant Lung Cancers

Sevabertinib received accelerated approval as first-line treatment for some lung cancers with HER2 activating mutations.

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to sevabertinib (Hyrnuo), for the treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with tumors that have activating mutations in the tyrosine kinase domain (TKD) of the human epidermal factor receptor 2 (HER2).

HER2 is a protein that regulates normal cell growth and survival, but is frequently altered in cancer. Activating mutations within the TKD put HER2 into a permanently active state, leading to uncontrolled cell growth and survival, promoting cancer.

Lungs with red tumor.

Sevabertinib is a tyrosine kinase inhibitor that reversibly and selectively inhibits mutant HER2 proteins, as well as mutant forms of the related epidermal growth factor receptor (EGFR). This drug was described in a preclinical study in the American Association for Cancer Research journal Cancer Discovery.

Prior to this approval, sevabertinib was given accelerated approval for patients who had received prior systemic therapy. This new accelerated approval expands its use to the first-line setting. Sevabertinib joins zongertinib (Hernexeos), which received a similar accelerated approval in February 2026, as a HER2 inhibitor for the first-line treatment of non-squamous NSCLC patients with HER2 TKD mutations.  

The accelerated approval of sevabertinib is based on results from SOHO-01, an open-label, single-arm, multicenter, multicohort clinical trial, the early results of which were reported in Cancer Discovery. Efficacy was evaluated in patients with locally advanced or metastatic, non-squamous NSCLC that had HER2 TKD activating mutations. Mutant HER2 were validated prior to enrollment in tumor tissue or plasma.

In a cohort of 69 patients, 75% had an objective response. Of those with responses, 73% had a response lasting for at least six months, while 38% had a response lasting for at least one year.

The recommended dosage of sevabertinib is 20 mg to be taken orally, twice daily with food, until disease progression or intolerable toxicity.

NSCLC accounts for approximately 85% of all lung cancer diagnoses, with HER2 mutations present in 2% to 4% of NSCLC cases. According to federal statistics, it was estimated that 229,410 individuals would be diagnosed with lung cancer and 124,990 patients would die of the disease in the in 2026, making it the deadliest cancer in the United States.

The FDA rendered its decision on September 9, 2026. Accelerated approval means that continued approval may be contingent upon a confirmatory trial. Please check this FDA web page for information about any accelerated approvals in oncology that may have been subsequently withdrawn and are no longer FDA-approved. Check this resource for updated information on all therapeutics regulated by the FDA.