FDA Expands Sevabertinib Approval to Treatment-Naive HER2-Mutant NSCLC

The FDA has granted accelerated approval to sevabertinib (Hyrnuo) for adult patients with locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.¹ The expanded indication removes the prior-therapy requirement that applied to the drug's original approval, making sevabertinib available to patients regardless of treatment history.^1,2

Efficacy and Safety Data

Efficacy in the treatment-naive population was evaluated in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort trial enrolling patients with locally advanced or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations, which were determined in tumor tissue or plasma by local laboratories prior to enrollment.1 The major efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR), assessed by blinded independent central review using RECIST v1.1.¹

Among 69 patients with locally advanced or metastatic NSCLC who had not received prior systemic therapy, the ORR was 75% (95% CI, 64%-85%). Of responding patients, 73% had a DOR of 6 months or longer, and 38% had a DOR of 12 months or longer.

The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. The recommended dose is 20 mg orally twice daily with food, continued until disease progression or unacceptable toxicity.

Previously Treated Indication Remains Unaffected

The expanded approval does not alter sevabertinib's existing indication for previously treated patients. The FDA first granted accelerated approval to sevabertinib in November 2025 for adults with locally advanced or metastatic, nonsquamous NSCLC with HER2 TKD activating mutations who had received at least 1 prior systemic therapy, and that population remains eligible for treatment under the original label.² The current action builds on that approval rather than replacing it, broadening eligibility to include patients at any line of therapy.^1,2

Regulatory Pathway

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that allows for concurrent submission and review of oncology drugs among international regulatory partners; for this application, the FDA collaborated with the United Kingdom's Medicines and Healthcare products Regulatory Agency, and reviews remain ongoing at the other participating agencies.¹ The review also used the Assessment Aid, a voluntary submission from the applicant intended to facilitate the FDA's assessment.

The application was granted priority review, and sevabertinib previously received breakthrough therapy designation and orphan drug designation.

REFERENCES

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non–small cell lung cancer. News release. FDA. September 9, 2026. Accessed September 9, 2026. https://tinyurl.com/ytes5udt

2. FDA grants accelerated approval to sevabertinib for non-squamous non–small cell lung cancer. News release. FDA. November 19, 2025. Accessed September 9, 2026. https://tinyurl.com/nhdr84b7