On November 19, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sevabertinib (Hyrnuo), a kinase inhibitor, for adults 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-approved test, and who have received a prior systemic therapy.
The FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 TKD activating mutations in patients with nonsquamous NSCLC who may be eligible for treatment with sevabertinib.
SOHO-01
Efficacy was evaluated in patients with unresectable or metastatic nonsquamous NSCLC with HER2 TKD activating mutations who had received prior systemic therapy and 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 70 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had received prior systemic therapy but were naive to therapy targeting HER2 mutations, the objective response rate was 71% (95% confidence interval [CI] = 59%–82%), with a median duration of response of 9.2 months (95% CI = 6.3–15.0 months), and 54% of responding patients having a duration of response lasting ≥ 6 months.
Among 52 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had received prior systemic therapy, including HER2-targeted antibody-drug conjugates, the objective response rate was 38% (95% CI = 25%–53%), with a median duration of response of 7.0 months (95% CI = 5.6 months to not evaluable), and 60% of responding patients having a duration of response lasting ≥ 6 months.
The prescribing information for sevabertinib includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
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 Health Canada, Israel’s Ministry of Health, and 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.
