FDA Approves Hyrnuo in Some with Locally Advanced/Metastatic NSCLC

The U.S. Food and Drug Administration has approved Hyrnuo (sevabertinib) for the treatment of adults with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) with HER2 tyrosine kinase domain activating mutations, according to a statement from the regulatory agency. The approval applies to patients who have previously received systemic therapy and whose tumors carry these mutations as identified through an FDA-approved test.

Notably, the agency also approved the Oncomine Dx Target Test as a companion diagnostic to help clinicians identify patients who may benefit from Hyrnuo, the statement stated, ensuring that patients receive therapy tailored to the molecular features of their disease.

New Accelerated Approval Provides a Targeted Option for HER2-Mutant NSCLC

The approval is supported by findings from the SOHO-01 clinical trial, an open-label and multi-center study that evaluated Hyrnuo in patients with unresectable or metastatic NSCLC. All participants had HER2 activating mutations and had received at least one prior systemic therapy. The trial measured outcomes that are important for patients, including confirmed objective response rate and duration of response. These measures reflect the proportion of patients whose tumors shrink and how long that benefit lasts.

Among patients who had not previously received HER2-targeted therapies, Hyrnuo produced an objective response rate of 71%. Responses were not only frequent but also durable, with a median duration of 9.2 months. More than half (54%) of responding patients continued to benefit for at least six months.

For patients who had been treated with HER2-targeted antibody–drug conjugates before entering the study, responses were more modest yet still clinically meaningful. The objective response rate in this group was 38%, with a median duration of response of 7.0 months. Notably, approximately 60% of responding patients maintained benefit for six months or longer.

Safety findings from the trial outlined several important considerations for patients. The prescribing information includes warnings for diarrhea, liver toxicity, interstitial lung disease or pneumonitis, ocular toxicity, elevations in pancreatic enzymes, and embryo-fetal toxicity risk. The recommended dose is 20 milligrams (mg) twice daily with food, continued until the disease progresses or side effects become unacceptable.

What Patients Should Know About Safety, Side Effects, and Dosing of Hyrnuo

Findings from the phase 1/2 SOHO-01 trial were presented at the European Society for Medical Oncology Congress, and highlighted the potential of Hyrnuo.

“Sevabertinib demonstrated robust and durable responses in patients with HER2-mutant NSCLC in both pretreated and first-line settings. The most common [side] effect was diarrhea, which was manageable; there were no reported cases of interstitial lung disease (ILD) or pneumonitis,” presenting study author Dr. Xiuning Le, associate professor in the Department of Thoracic/Head and Neck Medical Oncology of the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center, said in the presentation. “These data support sevabertinib as a potential new targeted therapy for patients with HER2-mutant NSCLC.”

Notably, in the ongoing phase 3 SOHO-02 trial, the agent is also being evaluated as a first-line approach for patients with locally advanced or metastatic NSCLC who also have HER2 mutations.

Hyrnuo is a kinase inhibitor developed to block the abnormal HER2 signaling pathway that drives tumor growth in patients with HER2 mutations. These mutations are less common than alterations in genes such as EGFR or ALK and represent a meaningful therapeutic target. Full prescribing information will be available through the FDA’s database.

References

1. “FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer,” by U.S. FDA. News release; Nov. 19, 2025.
2. “Sevabertinib Effective in Pretreated and First-Line HER2-Mutant NSCLC, by Tim Cortese. CURE; Oct. 17, 2025. https://www.curetoday.com/view/sevabertinib-effective-in-pretreated-and-first-line-her2-mutant-nsclc

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