The Ministry of Health, Labour and Welfare (MHLW) in Japan has approved sevabertinib (Hyrnuo) for the treatment of patients with HER2 mutation–positive unresectable advanced or recurrent non–small cell lung cancer (NSCLC), according to a news release from Bayer.¹ Sevabertinib is the first approved targeted therapy in Japan for this indication that can be used in any line of therapy, including as a first-line treatment. The approval is supported by data from the global phase 1/2 SOHO-01 trial (NCT05099172).
What did the SOHO-01 trial show?
Among patients with unresectable advanced or recurrent HER2-mutant NSCLC who had not received prior systemic therapy following diagnosis of advanced or recurrent disease (n = 73), the primary end point of objective response rate (ORR) was 75.3% (95% CI, 63.9%-84.7%). The median duration of response (DOR) was 12.2 months (95% CI, 8.8-not estimable), and the median progression-free survival (PFS) was 13.5 months (95% CI, 10.0-not estimable).
A manageable safety profile was noted with sevabertinib, with the most common adverse events (AEs) being diarrhea, rash, and paronychia. AEs leading to treatment discontinuation occurred in 3% of patients.
“HER2-mutant NSCLC remains an area of significant unmet medical need. Sevabertinib has demonstrated clinically meaningful efficacy together with a manageable safety profile and offers a promising new treatment option for these patients,” said Koichi Goto, PhD, chief of the Department of Thoracic Oncology at the National Cancer Center Hospital East in Japan, in the press release.¹
What is the SOHO-01 trial design?
SOHO-01 is an ongoing, global, phase 1/2 trial evaluating the efficacy and safety of sevabertinib in patients with advanced HER2-mutant NSCLC. Alongside SOHO-01, sevabertinib is being studied in the phase 3 SOHO-02 trial (NCT06452277) in patients who are treatment-naive with HER2-mutant NSCLC, as well as in the phase 2 panSOHO study (NCT06760819) in patients with metastatic or unresectable solid tumors harboring HER2-activating mutations apart from advanced NSCLC.
The primary end points of the SOHO-01 trial included treatment-emergent AEs, maximum tolerated dose, and ORR per RECIST v1.1 criteria and blinded independent central review.2 Secondary end points included disease control rate, DOR, PFS, and overall survival.
Patients 18 years and older with histologically or cytologically confirmed locally advanced NSCLC and documented disease progression on at least 1 prior systemic therapy for advanced disease were eligible for enrollment. Having measurable disease per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and a minimum life expectancy of 12 weeks were additional requirements for study entry.
What is sevabertinib and how does it work?
Sevabertinib is an oral, reversible, small-molecule tyrosine kinase inhibitor (TKI) that potently inhibits mutant HER2, including HER2 exon 20 insertions and HER2 point mutations, by blocking tyrosine kinases involved in cancer cell growth. According to the developers, reversible TKIs can temporarily block their targets, allowing for more precise control over treatment while potentially reducing long-term AEs compared with irreversible TKIs.
What is sevabertinib’s regulatory history in HER2-mutant NSCLC?
Previously, the FDA granted accelerated approval to sevabertinib for patients with previously treated advanced HER2-mutant NSCLC in November 2025.3 Additionally, the FDA granted the agent priority review as a first-line treatment in this population in May 2026.4 Sevabertinib was also approved earlier in 2026 by China’s National Medical Products Administration as monotherapy for patients with unresectable, locally advanced or metastatic HER2-activating–mutant NSCLC who had received 1 prior systemic therapy. The agent also holds breakthrough therapy designations for first- and second-line use from both the FDA and China’s Center for Drug Evaluation.5
References
- Bayer’s sevabertinib approved in Japan for patients with HER2-mutant non-small cell lung cancer. News release. Bayer. August 24, 2026. Accessed August 25, 2026. https://www.bayer.com/en/media
- First in human study of BAY2927088 in participants who have advanced non-small cell lung cancer (NSCLC) with mutations in the genes of epidermal growth factor receptor (EGFR) and/or human epidermal growth factor receptor 2 (HER2). ClinicalTrials.gov. Updated August 12, 2026. Accessed August 25, 2026. https://tinyurl.com/bdpvhm28
- FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. FDA. November 19, 2025. Accessed August 25, 2026. https://tinyurl.com/mt455knh
- U.S. FDA grants priority review to supplemental new drug application for HYRNUO (sevabertinib) under investigation as a first-line treatment of HER2-mutated non-small cell lung cancer. News release. Bayer. May 18, 2026. August 25, 2026. https://tinyurl.com/mtjducst
- Bayer receives breakthrough therapy designation in the U.S. and China for sevabertinib as a first-line treatment for patients with HER2-mutant non-small cell lung cancer. News release. Bayer. January 6, 2026. Accessed August 25, 2026. https://tinyurl.com/mrxedjzn
