On November 19, 2025, the Food and Drug Administration granted accelerated approval to sevabertinib (Hyrnuo, Bayer HealthCare Pharmaceuticals Inc.), a kinase inhibitor, for adults with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.
FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for treatment with sevabertinib.
Full prescribing information for Hyrnuo will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations who had received prior systemic therapy and received sevabertinib in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort clinical trial. HER2 (ERBB2) activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment.
The major efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR) as assessed by BICR using RECIST v1.1. Among 70 patients with locally advanced or metastatic NSCLC with HER2 (ERBB2) TKD activating mutations who had received prior systemic therapy but were naive to therapy targeting HER2 mutations, ORR was 71% (95% CI: 59, 82), with a median DOR of 9.2 months (95% CI: 6.3, 15.0), and 54% of responding patients having a DOR of ≥ 6 months.
Among 52 patients with locally advanced or metastatic NSCLC with HER2 (ERBB2) TKD activating mutations who had received prior systemic therapy including HER2-targeted antibody drug conjugates, ORR was 38% (95% CI: 25, 53), with a median DOR of 7.0 months (95% CI: 5.6, not evaluable), and 60% of responding patients having a DOR of ≥ 6 months.
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
Recommended Dosage
The recommended sevabertinib dose is 20 mg orally twice daily with food until disease progression or unacceptable toxicity.
Expedited Programs
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada (HC), Israel’s Ministry of Health, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. Sevabertinib received breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].
Follow the Oncology Center of Excellence on X: @FDAOncology.
