FDA Approves Sevabertinib for HER2-Mutant Non-Small Cell Lung Cancer

The US Food and Drug Administration (FDA) has granted accelerated approval to sevabertinib (Hyrnuo, Bayer Healthcare Pharmaceuticals Inc.), a targeted kinase inhibitor, for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors harbor HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.

This decision expands the existing indication for sevabertinib. The oral agent was previously granted accelerated approval for adult patients with locally advanced or metastatic non-squamous NSCLC with HER2 TKD activating mutations who had received prior systemic therapy. With this latest approval, sevabertinib is now available in the frontline setting for treatment-naive patients, offering a targeted oral option earlier in the disease course.

Clinical Efficacy in the SOHO-01 Trial

The accelerated approval was supported by efficacy data from SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort trial. The study evaluated sevabertinib in patients with locally advanced or metastatic non-squamous NSCLC harboring HER2 (ERBB2) TKD activating mutations, which were determined in tumor tissue or plasma by local laboratories prior to enrollment.

The major efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR). Among 69 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had not received prior systemic therapy, sevabertinib demonstrated clinically meaningful anti-tumor activity:

• Objective Response Rate: The confirmed ORR was 75% (95% CI: 64, 85).
• Durable Responses: Among responding patients, 73% maintained a DOR of 6 months or longer.
• Long-Term Benefit: A DOR of 12 months or longer was achieved by 38% of responding patients.

Key Nursing Takeaways: Dosing and Administration

Oncology nurses play an essential role in patient education, oral adherence counseling, and care coordination. Key administrative parameters include:

• Recommended Dosing Schedule: The recommended dose of sevabertinib is 20 mg taken orally twice daily with food until disease progression or unacceptable toxicity.
• Administration with Food: Nurses must emphasize to patients that sevabertinib must be taken with food to ensure proper drug absorption and therapeutic efficacy.
• Biomarker Verification: Prior to initiating treatment, nurses should confirm that an FDA-authorized diagnostic test has identified a HER2 (ERBB2) TKD activating mutation in tumor tissue or plasma.

Safety Profile and Toxicity Management

The prescribing information includes specific warnings and precautions for several potential adverse reactions. Because sevabertinib is an oral targeted therapy taken continuously at home, proactive nursing assessment and prompt toxicity management are critical to maintain patient safety and treatment continuity.

Key safety takeaways and monitoring guidelines for oncology nurses include:

• Gastrointestinal Monitoring: Diarrhea is a key warning; nurses should establish early management protocols, counsel patients on dietary adjustments, and instruct them to report severe symptoms.
• Pulmonary Vigilance: Nurses must monitor patients for new or worsening respiratory symptoms, such as dyspnea, cough, or fever, indicating interstitial lung disease (ILD) or pneumonitis.
• Organ Function and Enzyme Monitoring: Regular laboratory and clinical assessments are required to monitor for hepatotoxicity, left ventricular dysfunction, and pancreatic enzyme elevation.
• Ocular and Embryo-Fetal Toxicity: Nurses should instruct patients to report visual changes and counsel females of reproductive potential regarding embryo-fetal risks and appropriate contraception.

Global Regulatory Review and Reporting

The FDA review of sevabertinib was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology drugs with international regulatory partners. For this application, the FDA collaborated with the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA).

The application utilized the FDA's Assessment Aid and received Priority Review, Breakthrough Therapy designation, and Orphan Drug designation. Healthcare professionals should report any suspected serious adverse events to the FDA's MedWatch Reporting System or contact OCE's Project Facilitate for assistance with single-patient INDs.

Reference

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. US Food and Drug Administration. September 9, 2026. Accessed September 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small