Frontline Sevabertinib Earns FDA Priority Review in HER2-Mutated NSCLC

The FDA has granted priority review to a supplemental new drug application (sNDA) for frontline sevabertinib (Hyrnuo) among adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD)–activating mutations, according to a press release from the developer, Bayer.¹

The FDA previously granted accelerated approval to sevabertinib for patients with advanced or metastatic NSCLC harboring HER2 TKD-activating mutations who have received prior systemic therapy in November 2025.² Continued approval for this indication may depend on verification and description of clinical benefit in an additional trial. Sevabertinib is not yet available in the frontline setting.

Additionally, sevabertinib received breakthrough therapy designation from the FDA and China’s Center for Drug Evaluation as a frontline therapy for advanced or metastatic HER2-mutated NSCLC in January 2026.³

“The US FDA’s decision to grant priority review for [sevabertinib] is an important milestone as we continue to study this investigational treatment option in HER2-mutated [NSCLC],” Christian Rommel, PhD, head of Research and Development at Bayer’s Pharmaceuticals Division, stated in the press release.¹ “We look forward to working closely with regulatory authorities as they review the data supporting this application for use in the first-line setting.”

Supporting data for the priority review designation came from cohort F of the phase 1/2 SOHO-01 study (NCT05099172), in which patients without prior treatment received sevabertinib for locally advanced or metastatic HER2-mutant NSCLC. Investigators previously shared findings from the SOHO-01 study at the European Society for Medical Oncology (ESMO) Congress 2025.⁴

Among 73 evaluable patients in cohort F, the overall response rate per blinded independent central review (BICR) was 71% (95% CI, 59%-81%), which included complete responses in 4% and partial responses in 67%. Data showed a disease control rate (DCR) of 89% (95% CI, 80%-95%).

Across cohort F, 12% of patients had evaluable brain metastases. In patients with and without brain metastases in cohort F, respectively, the ORRs were 78% and 70%.

Regarding safety, 97% of patients in cohort F experienced a drug-related adverse event, and 21% experienced a grade 3 adverse event. It was also reported that 5% of cohort F had grade 3 diarrhea. Across the entire trial, no pneumonitis or interstitial lung disease was observed.

The primary end points of the SOHO-01 trial included treatment-emergent AEs, maximum tolerated dose, dose-limiting toxicities, and ORR per BICR using RECIST v1.1 criteria.⁵ Secondary end points included the recommended phase 2 dose, DCR, duration of response, progression-free survival, and overall survival.

Patients 18 years and older with histologically or cytologically confirmed locally advanced NSCLC, adequate archival tumor tissue, and measurable disease per RECIST v1.1 guidelines were eligible for enrollment on the trial. Other eligibility criteria included having documented EGFR and/or HER2 mutations per laboratory assessment, an ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks. Those who received prior EGFR tyrosine kinase inhibitors, had any history of primary brain or leptomeningeal disease, or a history of spinal cord compression or brain metastases were ineligible for enrollment on the trial.

“There continues to be progress in understanding and treating HER2-mutated NSCLC, and Bayer is committed to further investigating the full potential of [sevabertinib] as a treatment option. We appreciate the FDA’s priority review designation and remain focused on working through the regulatory process to help address the needs of this patient population,” Nelson Ambrogio, president of Bayer US Pharmaceuticals, concluded.¹

References

1. 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. Accessed May 18, 2026. https://tinyurl.com/mtjducst
2. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. News release. FDA. November 19, 2025. Accessed May 18, 2026. https://tinyurl.com/mt455knh
3. 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 May 18, 2026. https://tinyurl.com/mrxedjzn
4. Le X, Kim TM, Dong X, et al. Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): results from the SOHO-01 study. Presented at the 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA75.
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. Updated May 13, 2026. Accessed May 18, 2026. https://tinyurl.com/52bte8cm