Sevabertinib in HER2-Mutant NSCLC: Key Takeaways
•MHLW approval makes sevabertinib the first targeted therapy in Japan for HER2-mutant NSCLC usable across all lines of therapy, including first-line.
•First-line efficacy in SOHO-01 included a 75.3% ORR and 13.5-month median PFS (n = 73).
•Most common treatment-related adverse events were diarrhea, rash, and paronychia; 3% of patients discontinued treatment because of adverse events.
How was SOHO-01 designed?
SOHO-01 enrolled adult patients with locally advanced, recurrent or metastatic HER2-mutant NSCLC.2 Eligible patients received oral sevabertinib at 20 mg twice daily.
The primary end points were safety, determining the maximum tolerated and maximum administered doses, and ORR per RECIST 1.1 criteria by blinded independent central review. Secondary end points included DOR and PFS.
What was the safety profile observed in SOHO-01?
The SOHO-01 trial demonstrated a manageable safety profile in this population, with the most frequently observed adverse events being diarrhea, rash, and paronychia.¹ Adverse effects leading to treatment discontinuation occurred in 3% of patients.
How Does This Approval Fit Into Sevabertinib's Broader Regulatory History?
The Japanese approval follows sevabertinib's accelerated approval by the FDA in November 2025 for adult patients with previously treated, locally advanced or metastatic, nonsquamous NSCLC with HER2 tyrosine kinase domain–activating mutations, which was based on a 71% ORR (95% CI, 59%-82%) in HER2-targeted therapy–naive patients and a 38% ORR (95% CI, 25%-53%) in those previously treated with HER2-targeted antibody-drug conjugates.3
Earlier in 2026, sevabertinib was also approved by China's National Medical Products Administration as monotherapy for adult patients with unresectable, locally advanced, or metastatic NSCLC with HER2 activating mutations who had received one prior systemic therapy.¹ The agent previously received breakthrough therapy designation from the FDA and China's Center for Drug Evaluation for both first- and second-line use in advanced HER2-mutant NSCLC.
“The approval of sevabertinib by Japan’s MHLW marks an important advancement for patients with advanced HER2-mutant NSCLC, a patient population that has historically faced limited treatment options,” Christine Roth, executive vice president, Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team, at Bayer added in the news release.1 “Supported by results from the ongoing SOHO-01 study, this latest approval advances our precision oncology strategy and builds on earlier approvals in both the U.S. and China. We continue to work with clinicians and diagnostic partners to support timely HER2 testing and appropriate access in line with the approved indication, with the goal of improving outcomes for people living with this difficult-to-treat form of lung cancer.”
References
- Bayer's sevabertinib approved in Japan for patients with HER2-mutant non-small cell lung cancer. News release. Bayer AG. August 24, 2026. Accessed August 24, 2026. https://www.bayer.com/media/en-us/asset/1dbaf969-e7a9-4802-b068-14a2a2c2d819/2026-0134e
- Loong HH, Le X, Prelaj A, et al. SOHO-01: updated safety and efficacy of sevabertinib in patients with advanced HER2-mutant non-small cell lung cancer (NSCLC). J Clin Oncol. 2026;44(suppl 16):8622. doi:10.1200/JCO.2026.44.16_suppl.8622
- FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. FDA. November 19, 2025. Accessed August 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer