FDA Expands Sevabertinib Approval to First-Line HER2-Mutant Advanced Non-Small Cell Lung Cancer
Clinical Summary:
- Design/Population: The multicenter, open-label SOHO-01 trial evaluated sevabertinib in patients with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain activating mutations, including a cohort of previously untreated patients.
- Key Outcomes: Among previously untreated patients, sevabertinib produced a 75% objective response rate, with most responders maintaining their response for at least 6 months and more than one-third maintaining response for at least 12 months.
- Clinical Relevance: The expanded accelerated approval moves sevabertinib into the first-line setting for HER2-mutated advanced NSCLC, providing a targeted treatment option regardless of prior systemic therapy for patients with HER2 tyrosine kinase domain activating mutations.
On September 9, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to sevabertinib (Hyrnuo; Bayer Healthcare Pharmaceuticals Inc.) for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors harbor HER2 tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.
The approval expands the existing indication for sevabertinib into the first-line setting. Sevabertinib previously received accelerated approval for patients with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations following prior systemic therapy.
Efficacy was evaluated in the multicenter, open-label, single-arm, multi-cohort SOHO-01 trial, which enrolled patients with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations. HER2 mutation status was determined in tumor tissue or plasma by local laboratories before enrollment.
The major efficacy end points were confirmed objective response rate (ORR) and duration of response, as assessed by blinded independent central review according to RECIST version 1.1.
Among 69 patients who had not received prior systemic therapy, the confirmed ORR was 75%. Among responding patients, 73% maintained a response for at least 6 months and 38% maintained a response for at least 12 months.
The recommended sevabertinib dose is 20 mg orally twice daily with food until disease progression or unacceptable toxicity.
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 expanded accelerated approval establishes sevabertinib as a targeted treatment option for previously untreated patients with HER2 TKD-mutated locally advanced or metastatic non-squamous NSCLC, extending its use beyond patients who have received prior systemic therapy.
Source:
US Food and Drug Administration. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. Published online: 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
