FDA Approves Sevabertinib in HER2+ Non-Squamous NSCLC

The FDA has granted approval to sevabertinib (Hyrnuo) for the treatment of patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with HER2 tyrosine kinase domain (TKD-activating mutations identified by an FDA-approved test who have received prior systemic therapy.

With this approval, the FDA also greenlit the Oncomine Dx Target Test as a companion diagnostic device for the detection of HER2 (ERBB2) TKD-activating mutations in patients with non-squamous NSCLC who could be candidates for treatment with sevabertinib.

How Effective is Sevabertinib in HER2-Positive NS-NSCLC

The efficacy of sevabertinib in this patient population was assessed in the open-label, single-arm, multicenter, multi-cohort phase 1/2 SOHO-01 trial (NCT05099172), where it was observed that patients with this disease profile who were HER-targeting treatment-naive who received with sevabertinib (N = 70) had a confirmed objective response rate (ORR) of 71% (95% CI, 69%-82%).

Patients with locally advanced or metastatic NSCLC harboring HER2 (ERBB2) TKD-activating mutations also had a median duration of response (DOR) of 9.2 months (95% CI, 6.3-15.0) when treated with sevabertinib, and most patients (54%) had a DOR of at least 6 months.

Of 52 patients who received prior systemic therapy that included a HER2-targeting antibody-drug conjugate (ADC), ORR was 38% (95% CI, 2%-53%). The median DOR in these patients was 7.0 months (95% CI, 5.6-not evaluable [NE]), and 60% of patients had a DOR of at least 6 months.

Sevabertinib’s History in HER2-Positive NS-NSCLC

According to a press release from Bayer, the drug’s manufacturer, the oral, small molecule tyrosine kinase inhibitor (TKI) was granted priority review for this indication in May based on data from SOHO-01.The treatment was granted breakthrough therapy designation for this indication in 2024, according to the announcement.²

According to an additional news release published by Bayer, the results supporting the priority review designation came from data from October 14, 2024, on expansion cohorts D and E of SOHO-01, assessing patients naive to HER2-targeted therapies and patients previously treated with HER2-targeting antibody-drug conjugates, respectively, published in the Journal of Thoracic Oncology.^3,4 Cohorts D and E each received 20 mg of sevabertinib twice daily over the course of 3-week cycles.^3,5

The most common treatment-related adverse effects (TRAE) was diarrhea. While 16.7% of patients had grade 3 or higher diarrhea, no patient discontinued treatment due to diarrhea. TRAEs were reported in 97.4% of patients, and no patient developed interstitial lung disease. Sevabertinib had a manageable safety profile across cohorts. Additional TRAEs included rash (41.0%), nausea (25.6%), and paronychia (24.4%).

ORR was 70.5% (95% CI, 54.8%-83.2%) in the HER2 treatment-naive group and 35.3% (95% CI, 19.7%-53.5%) in the group where patients had previously received HER2-targeted therapies.

Disease control rates, defined as having stable disease or response for at least 12 weeks, were 81.8% for cohort D and 52.9% for cohort E. Likewise, median duration of response in cohorts D and E, respectively, were 8.7 months (95% CI, 4.5-not estimable [NE]) and 9.5 months (95% CI, 4.1-NE).

At the time of this assessment, 44 patients and 34 patients in cohorts D and E, respectively, were evaluated. In cohorts D and E, the median ages were 62.0 years and 62.5 years, 70.5% and 64.7% were nonsmokers, and 63.6% and 61.8% were female, respectively. The majority of both cohorts D (54.5%) and E (76.5%) had received at least 2 prior lines of therapy, and 82.4% of cohort E had received trastuzumab deruxtecan (Enhertu).

References

1. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
2. U.S. FDA accepts new drug application under priority review for sevabertinib (BAY 2927088) in HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed May 29, 2025. https://www.businesswire.com/news/home/20250528998636/en/U.S.-FDA-Accepts-New-Drug-Application-Under-Priority-Review-for-sevabertinib-BAY-2927088-in-HER2-Mutant-Non-Small-Cell-Lung-Cancer
3. Sevabertinib (BAY 2927088) granted FDA priority review for the treatment of patients with HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed May 29, 2025. https://www.bayer.com/media/en-us/sevabertinib-bay-2927088-granted-fda-priority-review-for-the-treatment-of-patients-with-her2-mutant-non-small-cell-lung-cancer/
4. Girard N, Loong HHF, Goh B-C, et al. 3O: Phase I/II SOHO-01 study of BAY 2927088 in patients with previously treated HER2-mutant NSCLC: safety and efficacy results from 2 expansion cohorts. J Thorac Oncol. 2025;20(3):S5-S6
5. 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. October 29, 2021. Updated May 13, 2025. Acccessed May 29, 2025. https://clinicaltrials.gov/study/NCT05099172