FDA Grants Accelerated Approval to Bayer's Hyrnuo (sevabertinib) as First-Line Therapy for HER2-Mutant NSCLC
核心洞察
The FDA granted accelerated approval to Bayer (搜索)'s oral TKI Hyrnuo (搜索) (sevabertinib (搜索)) for first-line treatment of locally advanced or metastatic non-squamous HER2 (搜索)-mutant NSCLC.
The decision, announced September 9, 2026, followed Priority Review and Breakthrough Therapy Designation and expands a November 2025 approval limited to previously treated patients.
Approval rests on the Phase I/II SOHO-01 trial's 69 treatment-naive patients, where objective response rate reached 75% (95% CI: 64-85) with 6% complete responses.
The U.S. Food and Drug Administration has granted accelerated approval to Bayer (搜索)'s Hyrnuo (搜索) (sevabertinib (搜索)) as a first-line treatment for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (搜索) (NSCLC) whose tumors carry HER2 (搜索) (ERBB2 (搜索)) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. The September 9, 2026 decision followed Priority Review and Breakthrough Therapy Designation and moves the oral therapy into the treatment-naive setting, where patients are typically the largest group in any indication.
The action expands a label that until now covered only previously treated patients. The FDA granted sevabertinib (搜索) its initial accelerated approval on November 19, 2025, for adults with the same biomarker-defined disease who had received prior systemic therapy. That earlier indication was based on objective response rate (ORR) and duration of response (DOR), and the new approval removes the prior-treatment requirement.
"The FDA's accelerated approval of sevabertinib (搜索) marks an important advance for treatment-naïve patients with HER2 (搜索)-mutated NSCLC who historically have a poor prognosis," said Xiuning Le, MD, PhD, SOHO-01 lead investigator and associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Le added that the milestone underscores the critical importance of comprehensive molecular testing at diagnosis, including for activating HER2 mutations, so that patients receive the most appropriate treatment as early as possible.
Christine Roth, Executive Vice President of Global Product Strategy and Commercialization and a member of Bayer (搜索)'s Pharmaceuticals Leadership Team, called the approval "a powerful validation of Bayer's commitment to advancing precision oncology in areas with the highest unmet needs." Roth noted that HER2 (搜索)-mutated NSCLC is a distinct subtype that often affects people who have never smoked, and that a critical need for additional treatment options remains.
SOHO-01 Cohort Data Support the Filing
The accelerated approval rests on Cohort F of the ongoing Phase I/II SOHO-01 trial (NCT05099172), an open-label, single-arm, multicenter, multi-cohort study evaluating sevabertinib (搜索) in patients with locally advanced or metastatic HER2 (搜索)-mutant NSCLC. The supporting cohort enrolled 69 treatment-naive patients; the primary endpoints were confirmed ORR and DOR.
Independent reviewers assessing scans under RECIST 1.1 criteria found a confirmed ORR of 75% (95% CI: 64–85), including complete responses in 6% of patients and partial responses in 70%. Among responders, 73% maintained a response for at least six months and 38% for at least 12 months, according to the FDA. Bayer (搜索) said the safety profile of sevabertinib (搜索) in this cohort was consistent with previous findings.
The agency based its decision on tumor-response results in this uncontrolled cohort rather than on a randomized comparison demonstrating a survival benefit over another treatment. The FDA's public summary did not provide overall-survival or progression-free-survival results for the previously untreated cohort, and the findings cannot establish how sevabertinib (搜索) compares with existing first-line approaches because the trial did not randomly assign patients to another medicine or regimen.
Continued approval for the first-line indication may be contingent on verification and description of clinical benefit in the ongoing Phase III SOHO-02 confirmatory trial (NCT06452277), which is evaluating sevabertinib (搜索) against standard of care in treatment-naive patients with advanced HER2 (搜索)-mutant NSCLC.
Mechanism, Dosing and Prior Global Approvals
Sevabertinib (搜索) is an oral, reversible, small molecule tyrosine kinase inhibitor that inhibits mutated human HER2 (搜索) — including HER2 exon 20 insertions and HER2 point mutations — as well as epidermal growth factor receptors (EGFR (搜索)), with selectivity for mutated versus wild-type EGFR. Bayer (搜索) states that reversible TKIs temporarily block their targets, which the company says allows more precise control over treatment and potentially reduces long-term side effects compared with irreversible TKIs. The compound is derived from Bayer's strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.
The recommended dose is 20 mg taken orally twice daily with food, continued until disease progression or unacceptable toxicity. The FDA conducted its review through Project Orbis, an international oncology-review initiative, in collaboration with the United Kingdom's Medicines and Healthcare products Regulatory Agency; reviews were continuing at other regulatory agencies.
Outside the United States, China's National Medical Products Administration approved sevabertinib (搜索) earlier in 2026 as monotherapy for adults with unresectable, locally advanced or metastatic NSCLC whose tumors have HER2 (搜索) activating mutations and who had received one prior systemic therapy. In Japan, the Ministry of Health, Labour and Welfare has approved sevabertinib as the first targeted therapy for this indication that can be used regardless of line of therapy, including as a first-line treatment, according to the company. Sevabertinib is also being studied in the panSOHO study (NCT06760819) in patients with metastatic or unresectable solid tumors with HER2-activating mutations, excluding advanced NSCLC.
Safety Profile and Monitoring Requirements
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, left ventricular dysfunction, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
In the pooled safety population, diarrhea was reported in 89% of patients who received Hyrnuo (搜索), including 16% Grade 3, with a median time to first onset of four days; dosage interruptions occurred in 15% of patients and dose reductions in 14%. Hepatotoxicity occurred in 29% of patients, including 3.1% Grade 3 and 0.3% Grade 4, while laboratory data showed increased alanine aminotransferase in 41% and increased aspartate aminotransferase in 44%. ILD/pneumonitis occurred in four patients (1.4%), including 0.3% Grade 3. Ocular toxicity occurred in 17% of patients, including one Grade 3 case of corneal epithelial microcysts with temporary unilateral blindness. Increased lipase occurred in 48% of patients, including 13% Grade 3 and 1.1% Grade 4, and increased amylase in 39%.
In SOHO-01, serious adverse reactions occurred in 33% of patients who received Hyrnuo (搜索); those in 2% or more of patients were diarrhea (3.7%), dyspnea (3.1%), vomiting (3.7%), pneumonia (2.6%), and pleural effusion (2.1%). A fatal adverse reaction of cerebral infarction occurred in one patient (0.5%). The most common adverse reactions (greater than 20%) were diarrhea (90%), rash (76%), stomatitis (37%), paronychia (36%), nausea (22%), and weight decreased (22%).
Sevabertinib (搜索) is a CYP3A substrate, and concomitant use with strong or moderate CYP3A inhibitors may increase plasma concentrations and the risk of adverse reactions; strong CYP3A inhibitors should be avoided. Concomitant use with strong or moderate CYP3A inducers may decrease effectiveness and should also be avoided. The drug is a weak to moderate CYP3A inhibitor, a P-gp inhibitor, and an in vitro inhibitor of CYP1A1.
Disease Burden and Competitive Landscape
Lung cancer remains the leading cause of cancer-related deaths worldwide, and NSCLC accounts for more than 85% of lung cancer cases. Activating HER2 (搜索) mutations are found in 2% to 4% of patients with advanced NSCLC, and 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes the disease difficult to treat.
Sevabertinib (搜索) enters a first-line HER2 (搜索)-mutated NSCLC landscape that now includes at least one other oral TKI. Boehringer Ingelheim's zongertinib (Hernexeos (搜索)) received U.S. FDA accelerated approval in the first-line HER2-mutated NSCLC setting in February 2026 and posted a 77% objective response rate in first-line treatment, close to sevabertinib's figure, though the two drugs were tested in different populations and trial designs.
For the November 2025 approval, the FDA also approved the Oncomine Dx Target Test from Life Technologies Corporation as a companion diagnostic to aid in detecting HER2 (搜索) (ERBB2 (搜索)) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for sevabertinib (搜索) treatment. That earlier review was conducted under Project Orbis in collaboration with Health Canada, Israel's Ministry of Health, and the UK's Medicines and Healthcare products Regulatory Agency, and sevabertinib received breakthrough and orphan drug designations.