Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Hyrnuo (sevabertinib) for the treatment of patients with HER2 (ERBB2) mutation-positive unresectable advanced or recurrent non-small cell lung cancer (NSCLC).
According to Bayer, Hyrnuo is the first targeted therapy approved in Japan for this indication that can be used regardless of line of therapy, including as a first-line treatment. Bayer announced the approval on August 24, 2026.
Sevabertinib is an oral, reversible, small-molecule tyrosine kinase inhibitor designed to target mutant HER2. The Japanese decision is supported by findings from the ongoing global Phase I/II SOHO-01 trial (NCT05099172) evaluating the treatment in patients with advanced HER2-mutant NSCLC.
SOHO-01 Data Supporting the Approval
The approval is supported by data from patients with unresectable advanced or recurrent HER2-mutant NSCLC who had not received prior systemic therapy following diagnosis of advanced or recurrent disease.
Among 73 patients, the primary endpoint of objective response rate (ORR) was 75.3%, with a 95% confidence interval of 63.9% to 84.7%.
The median duration of response (DOR) was 12.2 months (95% CI, 8.8 months to not estimable), while median progression-free survival (PFS) was 13.5 months (95% CI, 10.0 months to not estimable).
The most frequently observed adverse events were diarrhea, rash, and paronychia. Adverse events leading to treatment discontinuation occurred in 3% of patients.
Koichi Goto, PhD, Chief of the Department of Thoracic Oncology at the National Cancer Center Hospital East in Japan, described HER2-mutant NSCLC as an area of significant unmet medical need.
He highlighted the clinical activity and safety profile observed with sevabertinib and the significance of having the treatment available in the first-line setting without restriction by HER2 mutation subtype.
“The availability of sevabertinib in the first-line setting, without restriction by HER2 mutation subtype, marks an important step forward in expanding treatment choices for both patients and healthcare professionals.”
What Is Sevabertinib?
Sevabertinib is an oral, reversible TKI that potently inhibits mutant HER2, including HER2 exon 20 insertions and HER2 point mutations.
HER2, also known as ERBB2, is a receptor tyrosine kinase involved in signaling pathways regulating cell growth. Activating alterations can drive tumor development, making HER2 an actionable molecular target in a subset of cancers.
Sevabertinib works by inhibiting tyrosine kinase activity involved in cancer cell growth. The drug originated from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard.
Sevabertinib’s Regulatory Progress
The Japanese decision follows earlier regulatory milestones for sevabertinib in the United States and China.
On November 19, 2025, the U.S. Food and Drug Administration granted Hyrnuo accelerated approval for adults with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.
That U.S. approval was based on SOHO-01 and remains subject to confirmation of clinical benefit through a confirmatory trial. The FDA currently lists SOHO-02 as the study intended to verify and further describe the clinical benefit of sevabertinib.
Sevabertinib has also been approved by China’s National Medical Products Administration (NMPA) as monotherapy for adults with unresectable locally advanced or metastatic NSCLC harboring HER2-activating mutations who have received one prior systemic therapy.
The development program has additionally received Breakthrough Therapy Designations from the FDA and China’s Center for Drug Evaluation in both previously treated and first-line HER2-mutant NSCLC settings. In January 2026, Bayer announced that both agencies had granted Breakthrough Therapy Designation specifically for first-line use in locally advanced or metastatic HER2-mutant NSCLC.
In May 2026, the FDA also granted Priority Review to sevabertinib for first-line treatment of adults with locally advanced or metastatic NSCLC whose tumors harbor HER2 tyrosine kinase domain activating mutations.
The first-line U.S. application is based on preliminary clinical evidence from Cohort F of SOHO-01, which included patients who had not previously received treatment for advanced disease.
The Broader Clinical Development Program
Bayer is continuing to evaluate sevabertinib across several studies. The Phase III SOHO-02 trial (NCT06452277) is evaluating sevabertinib in treatment-naïve patients with HER2-mutant NSCLC. The study is intended to provide randomized Phase III evidence on the role of sevabertinib in the first-line setting.
Sevabertinib is also being evaluated in panSOHO (NCT06760819), a study involving patients with metastatic or unresectable solid tumors harboring HER2-activating mutations, excluding advanced NSCLC.
The Japanese approval adds another regulatory milestone for sevabertinib and expands the availability of molecularly targeted treatment for patients with HER2-mutant NSCLC, including those receiving systemic therapy for the first time.
Read further on OncoDaily: DESTINY-Lung04: Enhertu Improves First-Line PFS in HER2-Mutant NSCLC
