Sevabertinib Granted Accelerated Approval for Non-Squamous NSCLC
Expert Perspectives · Lyn Brook · 2025-11-24
The FDA has granted accelerated approval to the oral kinase inhibitor sevabertinib (Hyrnuo®, Bayer HealthCare Pharmaceuticals) for adults with locally advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA‑approved test, who have received at least one prior systemic therapy.
In addition, the FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic to aid in the detection of HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for sevabertinib.
Why This Approval Matters
HER2 (ERBB2) TKD activating mutations define a distinct molecular subset of non-squamous NSCLC associated with poor prognosis and historically limited targeted options, particularly for patients relapsing after prior systemic therapy and, in some cases, prior HER2-directed antibody-drug conjugates (ADCs). Sevabertinib provides an oral, mutation-directed kinase inhibitor option with clinically meaningful response rates and durations in both HER2 TKI–naive patients and those previously exposed to HER2-targeted ADCs. This approval reinforces the importance of routine molecular profiling, including HER2 TKD mutation testing, in advanced non-squamous NSCLC.
Breaking Down the SOHO-01 Trial
Efficacy was evaluated in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multicohort trial in patients with unresectable or metastatic, non-squamous NSCLC and HER2 (ERBB2) TKD activating mutations who had received prior systemic therapy. Prior to enrollment, local laboratories identified HER2 (ERBB2) activating mutations in tumor tissue or plasma.
The primary end points were confirmed objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review using RECIST v1.1. Two key populations were analyzed:
- This first population analyzed consisted of 70 patients with locally advanced or metastatic NSCLC and HER2 TKD activating mutations who had received prior systemic therapy and were naive to therapy targeting HER2 mutations. The ORR was 71%, median DOR was 9.2 months, and 54% of responders maintained a response for at least six months.
- The second population consisted of 52 patients with locally advanced or metastatic NSCLC and HER2 TKD activating mutations who had received prior systemic therapy including HER2-targeted ADCs. The ORR was 38%, median DOR was 7.0 months, and 60% of responders had a DOR ≥6 months.
Managing Adverse Events
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. These toxicities warrant proactive monitoring, dose modification as needed, and patient counseling, particularly regarding respiratory symptoms, visual changes, and reproductive risk.
Dosing and Administration
The recommended dosage of sevabertinib is 20 mg orally, twice daily with food, continued until disease progression or unacceptable toxicity.