FDA Approves Sevabertinib for First-Line Treatment of Advanced HER2-Mutant Lung Cancer

The FDA has granted accelerated approval to sevabertinib as first-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer with activating mutations in the HER2 tyrosine kinase domain (TKD). In patients who had never received systemic therapy, the objective response rate was 75%.

9 September 2026 — The U.S. Food and Drug Administration (FDA) announced accelerated approval of the targeted agent sevabertinib (Hyrnuo) for the first-line treatment (no prior systemic therapy) of patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations in the HER2 tyrosine kinase domain (TKD).

This new decision substantially broadens the drug's existing indication. In November 2025, sevabertinib was approved in the same patient group only for those who had already received systemic therapy (second or later line). With the new approval, the agent has become a standard option for the initial treatment of patients whose HER2 TKD mutation is detected by an FDA-approved test.

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The SOHO-01 Clinical Trial and Response Rates

The FDA's decision is based on efficacy data from SOHO-01 (NCT05099172), an open-label, single-arm, multicenter clinical trial. Patients' HER2 mutation status was analyzed from tumor tissue or plasma (liquid biopsy) before enrollment.

• Objective Response Rate (ORR): In the trial, which evaluated 69 patients with locally advanced or metastatic NSCLC who had never received any systemic therapy, the ORR reached a high 75%.
• Response lasting 6 months or longer: Among patients who responded to treatment, the response lasted 6 months or longer in 73%.
• Response lasting 12 months or longer: In 38% of responders, the benefit was reported to last 12 months or longer (Duration of Response, DoR).

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Safety and Side Effect Profile

The recommended standard dose of sevabertinib is 20 mg tablets taken orally twice daily with food, until disease progression or unacceptable toxicity.

The prescribing information contains warnings advising physicians and patients to be alert to the following risks:

• Diarrhea
• Liver toxicity (hepatotoxicity)
• Interstitial lung disease / pneumonitis
• Left ventricular dysfunction
• Eye (ocular) toxicity
• Pancreatic enzyme elevation
• Embryo-fetal toxicity

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Simultaneous International Review: Project Orbis

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that enables international health authorities to review cancer drugs concurrently. The drug was evaluated with Priority Review, Breakthrough Therapy and Orphan Drug designations.

💬 Important Information for Our Patients

We would like to note that this next-generation drug containing the active substance sevabertinib has, for now, been approved only by the U.S. Food and Drug Administration (FDA). The drug does not yet have a marketing authorization in Turkey, and unfortunately it is not known at this stage when it will be made available to patients in our country. Our clinic continues to follow such promising developments in the field of oncology closely on behalf of our patients.

Conclusion

Shortly after its first approval for later lines in November 2025, sevabertinib has now moved into the first-line setting. A response in three out of four previously untreated patients shows once again how decisive it is for treatment selection to test for HER2 TKD mutations at diagnosis, using tissue or liquid biopsy. Whether the accelerated approval becomes permanent will depend on the results of ongoing confirmatory trials.

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References

• The ASCO Post. (9 September 2026). NSCLC: FDA Grants Accelerated Approval to Sevabertinib for Locally Advanced or Metastatic Nonsquamous Disease.
• ClinicalTrials.gov. SOHO-01: A Study of Sevabertinib in Patients With NSCLC and HER2 Mutations. U.S. National Library of Medicine. ClinicalTrials.gov Identifier: NCT05099172.