Sevabertinib Given FDA Priority Review for HER2+ NSCLC

The FDA gave sevabertinib breakthrough therapy designation for HER2-positive NSCLC in 2024.

The new drug application (NDA) seeking the approval of sevabertinib (BAY2927088) in previously treated HER2-positive non-small cell lung cancer (NSCLC) was granted priority review by the FDA, according to a press release from Bayer, the drug’s developer.¹

The oral, small molecule tyrosine kinase inhibitor (TKI) is currently being investigated in the multicenter phase 1/2 SOHO-01 trial (NCT05099172), results from which supported the NDA. The treatment was granted breakthrough therapy designation for this indication in 2024, according to the announcement.

“The FDA’s decision to grant priority review designation to our application for sevabertinib is a significant milestone that supports our ongoing efforts to develop healthcare solutions that help people living with lung cancer,” said Christine Roth, executive vice president of global product strategy and commercialization at Bayer, in the release. “If approved, sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2-activating mutation.”

Roth, a member of Bayer’s pharmaceuticals leadership team, also noted in the release that HER2-mutated NSCLC more often occurs in women, non-smokers, and younger patients.

The primary end point of SOHO-01 is the maximum tolerated dose of sevabertinib, with a secondary end point of objective response rate (ORR).² Patients had experienced disease progression after at least 1 prior line of systemic therapy for advanced disease and harbored documented EGFR or HER2 mutations. Additionally, patients were required to have an ECOG status of 0 or 1. SOHO-01 consists of dose escalation, backfill, dose expansion, and extension parts.

Preliminary Data Leading to Priority Review

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 (ADCs), 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.^2,3

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 non-smokers, 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).

As noted in the press release, NSCLC is the most common type of lung cancer, of which 2%-4% of cases contain HER2 mutations.

References

1. U.S. FDA accepts new drug application under priority review for sevabertinib (BAY 2927088) in HER2-nutant non-small cell lung cancer. Bayer. News release. 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
2. 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
3. Sevabertinib (BAY 2927088) granted FDA priority review for the treatment of patients with HER2-mutant non-small cell lung cancer. Bayer. News release. 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