FDA Grants Accelerated Approval to Bayer's HYRNUO (sevabertinib) as First-Line Therapy for HER2-Mutated NSCLC
核心洞察
The FDA granted accelerated approval to Bayer (搜索)'s oral tyrosine kinase inhibitor HYRNUO (搜索) (sevabertinib (搜索)) for treatment-naive adults with locally advanced or metastatic nonsquamous NSCLC harboring HER2 (搜索) TKD activating mutations.
Approval was based on SOHO-01 Cohort F data showing a 75% objective response rate (95% CI: 64%-85%) in 69 treatment-naive patients, with 73% of responders maintaining response at six months.
The indication expands sevabertinib (搜索)'s existing November 2025 accelerated approval, which covered patients with HER2 (搜索) TKD activating mutations who had received prior systemic therapy.
The U.S. Food and Drug Administration has granted accelerated approval to Bayer (搜索)'s HYRNUO (搜索) (sevabertinib (搜索)) for adult patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors carry human epidermal growth factor receptor 2 (HER2 (搜索)/ERBB2 (搜索)) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. The approval, announced Thursday, expands the agent's existing indication to include patients with treatment-naive disease.
Sevabertinib (搜索) is an oral, reversible, small-molecule tyrosine kinase inhibitor (TKI). The recommended dose is 20 mg administered orally twice daily with food, continued until disease progression or unacceptable toxicity.
Prior Approval and Expanded Indication
The new approval broadens an earlier accelerated approval granted in November 2025 for adult patients with locally advanced or metastatic nonsquamous NSCLC with HER2 (搜索) TKD activating mutations who had received prior systemic therapy. With this action, sevabertinib (搜索) becomes the first-line treatment option for the eligible treatment-naive population.
SOHO-01 Efficacy Data
Efficacy was evaluated in the ongoing Phase I/II SOHO-01 trial (ClinicalTrials.gov identifier NCT05099172), an open-label, single-arm, multicenter, multicohort study assessing the safety and efficacy of sevabertinib (搜索) in patients with locally advanced or metastatic nonsquamous HER2 (搜索)-mutated NSCLC. 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 (ORR) and duration of response (DOR), as assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1.
Among 69 treatment-naive patients (Cohort F) with locally advanced or metastatic NSCLC and HER2 (搜索) TKD activating mutations, sevabertinib (搜索) achieved an ORR of 75% (95% CI: 64%–85%). Responses included complete responses in 6% of patients (n=4) and partial responses in 70% (n=48). Among responders, 73% maintained their response for at least six months and 38% for at least 12 months.
Safety Profile
The safety profile of sevabertinib (搜索) was consistent with earlier reports. Among 191 patients treated in the SOHO-01 study, the most common adverse reactions (≥20%) included rash, stomatitis, paronychia, diarrhoea, nausea, and weight loss.
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.
Confirmatory Trial and Regulatory Designations
Continued approval for this indication may depend on verification of clinical benefit in the ongoing Phase III SOHO-02 trial, which compares sevabertinib (搜索) with standard of care in treatment-naive patients with advanced HER2 (搜索)-mutated NSCLC.
The application was granted Priority Review, and sevabertinib (搜索) received both Breakthrough Therapy designation and Orphan Drug designation. The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that 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, with application reviews ongoing at other regulatory agencies. The review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA's assessment.
Market Context
According to Market Research Future, the global non-small cell lung cancer (搜索) market was valued at an estimated $20.9 billion in 2024 and is projected to reach $32.52 billion by 2035.