FDA Approves Sevabertinib for Nonsquamous NSCLC

The FDA has granted an accelerated approval for the use of sevabertinib (Hyrnuo; Bayer) in patients with nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations.¹ The approval allows for patients to take sevabertinib in a 20-mg oral dose twice per day.

The accelerated approval was based on results from the SOHO-01 (NCT05099172) trial that enrolled patients with unresectable or metastatic nonsquamous NSCLC who had HER2 (ERBB2) TKD activating mutations. The trial was open-label and was conducted in multiple centers. Tumor tissue and plasma were used to determine who had HER2 (ERBB2) activating mutations. The primary end points were objective response rate (ORR) and duration of response (DOR).

There were 70 patients who had received prior systemic therapy and were naïve to therapies that targeted HER2 mutations. They had an ORR of 71% (95% CI, 59%-82%). The median DOR for this group was 9.2 months (95%, 6.3-15.0); a DOR of at least 6 months was reported in 54% of the individuals included in this group.

There were 52 patients with NSCLC who had been treated with both systemic therapy and therapies that had targeted HER2 mutations. The ORR was lower in this group, at only 38% (95% CI, 25%-53%). The DOR was also slightly shorter at 7.0 months (95% CI, 5.6-not evaluable), but 60% of the individuals had a DOR of at least 6 months, which was higher than in those who were naïve to therapies that targeted HER2 mutations.

All participants of the study had reported adverse events, with drug-related adverse events reported in 96% of all patients in the study, with 31% experiencing a drug-related adverse event that was grade 3 or higher.² Diarrhea was the most commonly reported adverse event in the study, of which 5% to 23% was rated as grade 3 or higher. A total of 3% of the participants discontinued treatment due to their adverse events related to the drug.

This FDA approval marks the first time that the FDA has approved sevabertinib across the world.³ Sevabertinib had been granted priority review for their new drug application in May 2025 due to positive results in the phase I and II SOHO-01 trial. It was granted Breakthrough Therapy designation in 2024 and was available to use in unresectable or metastatic NSCLC with HER2 (ERBB2) mutations who had previously received systemic therapy.

“The FDA’s decision to grant Priority Review designation to our application for sevabertinib is a significant milestone that supports our ongoing efforts to develop healthcare solutions that help people living with lung cancer. If approved, sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2-activating mutation,” Christine Roth, the executive vice president of Global Product Strategy and Commercialization at Bayer, had said at the time.³

The FDA recommends that patients using sevabertinib receive the treatment twice per day with food at a 20 mg dose. All patients should receive the treatment until either unacceptable toxicity or disease progression.

References

1. FDA grants accelerated approval to sevabertinib for non-squamous non–small cell lung cancer. News release. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer

2. Le X, Kim TM, Loong HH, et al. Sevabertinib in advanced HER2-mutant non–small-cell lung cancer. N Engl J Med. 2025;393:1819-1832. doi:10.1056/NEJMoa2511065

3. US FDA accepts new drug application under priority review for sevabertinib (BAY 2927088) in HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed November 19, 2025. https://www.bayer.com/en/us/news-stories/sevabertinib