Today, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sevabertinib (Hyrnuo), a kinase inhibitor, for adult patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.
This approval expands the existing indication for sevabertinib to include patients with treatment-naive disease. The agent was previously granted accelerated approval in November 2025 for adult patients with locally advanced or metastatic nonsquamous NSCLC with HER2 TKD activating mutations who had received prior systemic therapy.
SOHO-01
Efficacy was evaluated in patients with locally advanced or metastatic, nonsquamous NSCLC with HER2 TKD activating mutations who received sevabertinib in SOHO-01 (ClinicalTrials.gov identifier NCT05099172), an open-label, single-arm, multicenter, multicohort clinical trial. HER2 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 and duration of response as assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1. Among 69 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had not received prior systemic therapy, the objective response rate was 75% (95% confidence interval = 64%–85%); 73% of responding patients had a duration of response of ≥ 6 months and 38% had a duration of response of ≥ 12 months.
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.
Recommended Dosage
The recommended sevabertinib dose is 20 mg orally twice daily with food until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the United Kingdom’s Medicines and Healthcare products Regulatory Agency. 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 Therapy designation and Orphan Drug designation.
