FDA Grants Accelerated Approval to Sevabertinib for Advanced HER2-Mutant Non-Squamous NSCLC
Non small cell lung cancer (NSCLC) is the most common form of lung cancer and remains a leading cause of cancer related mortality worldwide. Activating HER2 mutations occur in approximately 2% to 4% of advanced NSCLC cases, defining a distinct molecular subgroup that frequently affects individuals who have never smoked. Patients with HER2 mutant NSCLC typically face a poor clinical prognosis and, until recently, have had limited targeted treatment options (1).
Unmet Needs in Molecularly Defined NSCLC
Patients with advanced HER2 mutant NSCLC have historically faced limited targeted treatment options, leaving a significant unmet need for effective therapies in both treatment naïve and previously treated populations. Clinical experts emphasize that comprehensive molecular testing early in the diagnostic evaluation, including assessment for activating HER2 alterations, is essential to identify eligible patients and enable the delivery of appropriate precision therapies (1).
FDA Approval of Sevabertinib
On September 9, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sevabertinib (Hyrnuo, Bayer HealthCare Pharmaceuticals Inc.) as a targeted first line treatment for adults with locally advanced or metastatic non squamous non small cell lung cancer (NSCLC) harboring HER2/ERBB2 tyrosine kinase domain (TKD) activating mutations (1). This approval builds on the earlier November 19, 2025 accelerated approval of sevabertinib for adults with pretreated HER2 mutant non squamous NSCLC who had received prior systemic therapy. Sevabertinib is an oral, reversible, small molecule tyrosine kinase inhibitor (TKI), and its regulatory review was conducted under Priority Review and Breakthrough Therapy Designations (1,2).
Sevabertinib: Drug Profile & Clinical Evidence
Sevabertinib is an oral, reversible tyrosine kinase inhibitor (TKI) that targets mutant HER2 proteins, thereby blocking HER2 signaling pathways involved in tumor growth (1).
Frontline approval was supported by efficacy results from a treatment naïve cohort (N=69) in the ongoing Phase I/II SOHO 01 trial (NCT05099172). In this cohort, sevabertinib achieved an objective response rate (ORR) of 75% (95% CI: 64–85), including complete responses in 6% and partial responses in 70% of patients; notably, 73% of responders maintained their response for ≥6 months (1-3).
In pretreated patients naïve to HER2 targeted therapy (N=70), SOHO 01 demonstrated an ORR of 71% (95% CI: 59–82) with a median duration of response (DOR) of 9.2 months (95% CI: 6.3–15.0) (1,2). Among pretreated patients previously exposed to HER2 targeted antibody drug conjugates (N=52), sevabertinib achieved an ORR of 38% (95% CI: 25–53) and a median DOR of 7.0 months (95% CI: 5.6–NE) (1-3).
To support clinical implementation, the FDA also approved the Oncomine Dx Target Test as a companion diagnostic for detecting HER2 (ERBB2) TKD activating mutations in patients eligible for sevabertinib therapy (1).
Clinical Benefits & Indications
Sevabertinib is indicated for adults with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations detected by an FDA-authorized test (1,2). The recommended dosage is 20 mg orally twice daily with food, continued until disease progression or unacceptable toxicity (1).
Under Project Orbis, regulatory reviews are ongoing in Canada, Israel, and the United Kingdom (1,2).
Safety Profile & Precautions
The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, and interstitial lung disease (ILD)/pneumonitis. Additional precautions include ocular toxicity, pancreatic enzyme elevations, and embryo-fetal toxicity. Suspected adverse reactions should be reported through the FDA MedWatch Reporting System (1).
Clinical Perspective
Sevabertinib provides an oral targeted treatment option for adults with advanced HER2-mutant non-squamous NSCLC (1,2). As an accelerated approval, continued approval for the frontline indication may depend on verification of clinical benefit in the ongoing Phase III SOHO-02 trial (NCT06452277), which is comparing sevabertinib with standard of care. In addition, the panSOHO study (NCT06760819) is evaluating sevabertinib across other HER2-mutant solid tumors, potentially further defining its clinical application in HER2-driven malignancies (2).
About the Author
Dr. Manisha Dadlani is a Dental Surgeon and Medical Writer with 5+ years of clinical experience and formal training in medical writing. She combines clinical expertise with analytical thinking to develop evidence-based, insight-driven content that supports effective scientific communication across the healthcare and life sciences landscape.
References:
Bayer AG. U.S. FDA grants accelerated approval to Bayer’s targeted therapy sevabertinib as a first-line treatment option for adults with HER2-mutant non-small cell lung cancer. Available at: https://www.bayer.com/media/en-us/us-fda-grants-accelerated-approval-to-bayers-targeted-therapy-sevabertinib-as-a-first-line-treatment-option-for-adults-with-her2-mutant-non-small-cell-lung-cancer/ Accessed on 21 September, 2026.
U.S. Food and Drug Administration (FDA). FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. Available at:
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer Accessed on 21 September, 2026.
Zhou C, Mok TSK, Li BT, et al. Phase I/II study of sevabertinib (Hyrnuo), an oral HER2 tyrosine kinase inhibitor, in patients with HER2 mutant non small cell lung cancer (SOHO 01). Lancet Oncol. 2026;27(8):945 57.
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