Bayer’s sevabertinib receives Breakthrough Therapy Designation from the U.S. FDA and China’s CDE as a first-line treatment for advanced HER2-mutant non-small cell lung cancer, supported by early SOHO-01 trial data and recent FDA accelerated approval.
Written By: Nikita Chaudhari, BPharm
Reviewed By: Pharmacally Editorial Team
Bayer announced that sevabertinib has been granted Breakthrough Therapy Designation by both the U.S. Food and Drug Administration and China’s Center for Drug Evaluation. The designation applies to sevabertinib as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating human epidermal growth factor receptor 2 (HER2) mutations.
This dual regulatory recognition reflects the urgent need for more effective first-line options in HER2-mutant NSCLC, a disease area with limited approved therapies and historically poor outcomes.
Sevabertinib and its targeted mechanism
Sevabertinib is an oral, reversible, small molecule tyrosine kinase inhibitor designed to selectively inhibit mutant HER2, including HER2 exon 20 insertions and HER2 point mutations. The drug also inhibits epidermal growth factor receptor (EGFR) with high selectivity for mutant forms over wild-type EGFR.
By reversibly blocking tyrosine kinases involved in tumor growth and survival, sevabertinib aims to provide precise pathway inhibition while potentially reducing long-term toxicity compared with irreversible TKIs. This selectivity is particularly relevant in lung cancer, where treatment-related adverse events often limit sustained therapy.
Clinical evidence supporting Breakthrough designation
The Breakthrough Therapy Designations are supported by preliminary clinical data from cohort F of the ongoing Phase I/II SOHO-01 study (NCT05099172). Cohort F includes patients with locally advanced or metastatic HER2-mutant NSCLC who had not received prior systemic treatment.
Early results from this treatment-naïve population demonstrated clinically meaningful antitumor activity and a safety profile that regulators considered favourable enough to justify expedited development. These findings suggest sevabertinib may offer advantages over existing first-line treatment options.
Regulatory context and recent FDA approval
The Breakthrough Therapy Designations follow a recent regulatory milestone for sevabertinib in the United States. In November 2025, sevabertinib received FDA accelerated approval under the brand name Hyrnuo™ for patients with previously treated advanced HER2-mutant NSCLC.
That approval was based on objective response rate and duration of response data from the SOHO-01 trial, including cohort D, which enrolled previously treated patients without prior HER2-targeted therapy, and cohort E, which included patients previously treated with HER2-directed antibody-drug conjugates.
Ongoing and planned clinical development
Beyond SOHO-01, sevabertinib is being evaluated in the Phase III SOHO-02 trial (NCT06452277), which is studying the drug as a first-line treatment in patients with HER2-mutant NSCLC. Bayer is also conducting the panSOHO study (NCT06760819), a multi-tumor trial evaluating sevabertinib in patients with metastatic or unresectable solid tumors harboring HER2-activating mutations, excluding advanced NSCLC.
Sevabertinib originated from Bayer’s strategic research collaboration with the Broad Institute of MIT and Harvard, highlighting the role of academic-industry partnerships in advancing precision oncology.
Commenting on the announcement, Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division, said the Breakthrough Therapy Designations underscore sevabertinib’s potential as a first-line option in advanced HER2-mutant NSCLC. He noted that the designations, together with the earlier accelerated approval in previously treated patients, reflect Bayer’s focus on developing personalized therapies to address critical unmet needs and improve survival outcomes.
Disease background
Lung cancer remains the leading cause of cancer-related mortality worldwide. NSCLC accounts for more than 85 percent of all lung cancer cases and activating HER2 mutations are present in approximately 2 to 4 percent of patients with advanced disease.
Around 80 percent of patients with NSCLC are diagnosed at an advanced stage, where curative treatment is rarely possible. For patients with HER2-mutant NSCLC, treatment options remain limited, reinforcing the need for effective, targeted first-line therapies.
With Breakthrough Therapy Designation in both the U.S. and China, sevabertinib is positioned for accelerated development and closer regulatory interaction. If ongoing trials confirm its clinical benefit, sevabertinib could redefine first-line treatment for HER2-mutant NSCLC and expand the role of precision medicine in lung cancer care.
Reference
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, 06 January 2026, https://www.bayer.com/media/en-us/bayer-receives-breakthrough-therapy-designation-in-the-us-and-china-for-sevabertinib-as-a-first-line-treatment-for-patients-with-her2-mutant-non-small-cell-lung-cancer/
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 ID NCT05099172, https://clinicaltrials.gov/study/NCT05099172
Le X, et al, Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2025 Nov 6;393(18):1819-1832. Doi: 10.1056/NEJMoa2511065. Epub 2025 Oct 17. PMID: 41104928.
A Study to Learn More About How Well Treatment with Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor with Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) (panSOHO), ClinicalTrials.gov ID NCT06760819, https://clinicaltrials.gov/study/NCT06760819
A Study to Learn More About How Well Sevabertinib (BAY 2927088) Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) (SOHO-02), ClinicalTrials.gov ID NCT06452277, https://www.clinicaltrials.gov/study/NCT06452277