FDA Approves Sevabertinib for Advanced HER2 TKD–Mutated Nonsquamous NSCLC

The FDA has granted accelerated approval to sevabertinib (Hyrnuo) for the treatment of adult patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors harbor HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.¹

This approval was supported by data from the open-label, single-arm, multicenter, multi-cohort SOHO-01 trial (NCT05099172) of sevabertinib in patients with locally advanced or metastatic, nonsquamous NSCLC with HER2 (ERBB2) TKD activating mutations, which were identified in tumor tissue or plasma by local laboratories before enrollment. Among evaluable patients who had not been treated with prior systemic therapy (n = 69), the overall response rate (ORR) was 75% (95% CI, 64%-85%). Additionally, 73% of responders achieved a duration of response (DOR) of at least 6 months, and 38% of responders had a DOR lasting at least 12 months.

This regulatory decision expands the existing indication for sevabertinib, which was granted accelerated approval in November 2025 for the treatment of adult patients with locally advanced or metastatic nonsquamous NSCLC with HER2 (ERBB2) TKD activating mutations who have received prior systemic therapy.

What was the design of the SOHO-01 trial?

SOHO-01 was designed to investigate the efficacy and safety of the oral, reversible, small molecule TKI sevabertinib in patients with unresectable or metastatic nonsquamous NSCLC harboring HER2 (ERBB2) TKD activating mutations. ORR served as a primary efficacy end point.² Secondary end points included DOR, progression-free survival (PFS), and safety.

What additional efficacy data from SOHO-01 are important to note?

Among evaluable treatment-naive patients (n = 73), the median progression-free survival was NE (95% CI, 9.6-NE) and the disease control rate was 89% (95% CI, 80%-95%).

References

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. FDA. September 9, 2026. Accessed September 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small
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(18):1819-1832. doi:10.1056/NEJMoa2511065