Following Priority Review and Breakthrough Therapy Designation, the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Hyrnuo (sevabertinib), for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have human epidermal growth factor receptor 2 (HER2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. Sevabertinib is an oral, reversible, small molecule, tyrosine kinase inhibitor (TKI).
“The FDA’s approval of sevabertinib elevates the standard of care and provides a new treatment option for patients living with HER2-mutant NSCLC, which is a challenging disease with limited therapies available,” said SOHO-01 lead trialist, Xiuning Le, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, Texas. “Clinical results from the SOHO-01 trial showed that sevabertinib is effective with a manageable safety profile.”
The FDA approved this indication for sevabertinib under accelerated approval based on objective response rate (ORR) and duration of response (DOR) data from the ongoing Phase I/II SOHO-01 trial (NCT05099172) in patients with advanced NSCLC harboring a HER2-activating mutation, with disease progression after ≥1 systemic therapies for advanced disease. Continued approval of sevabertinib for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Results from the Phase I/II SOHO-01 trial demonstrated for patients naïve to HER2 targeted therapy an ORR of 71% (95% CI: 59%-82%, N=70); 2.9% of patients had a complete response and 69% of patients had a partial response. Median DOR was 9.2 months (95% CI, 6.3–15.0, N=50). Sevabertinib demonstrated a manageable safety profile with a 3.7% discontinuation rate. In the pooled safety population, the most common (> 20%) adverse reactions were diarrhea (87%), rash (66%), paronychia (33%), stomatitis (29%) and nausea (21%).
Positive results from the Phase I/II SOHO-01 trial were presented at the European Society for Medical Oncology (ESMO) Congress 2025 and simultaneously published in the New England Journal of Medicine.0F[1]
“Globally, it is estimated that up to 84,000 people are diagnosed with NSCLC harboring a HER2 mutation each year,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “At Bayer our oncology R&D strategy is centered on precision drug development which is designed to help us address critical unmet medical needs through the advancement of innovative therapies. Today's FDA approval of sevabertinib exemplifies this approach, delivering a targeted treatment specifically for patients with advanced HER2-mutant NSCLC. This significant milestone underscores our unwavering commitment to transforming cancer care by delivering meaningful therapies that have the potential to improve outcomes and extend survival for people living with cancer.”
In 2024, both the U.S. FDA and the CDE in China granted sevabertinib Breakthrough Therapy designation indicating that the compound has the potential to provide substantial improvement over existing therapies in NSCLC with HER2-activating mutations. China accepted a new drug application (NDA) for sevabertinib in July 2025.
https://en.wikipedia.org/wiki/Sevabertinib
