Sevabertinib — Drug Monograph

Brand names: Hyrnuo

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Sevabertinib is an oral, reversible, HER2 (ERBB2)-selective tyrosine kinase inhibitor targeting HER2 tyrosine kinase domain activating mutations in NSCLC, with selectivity for mutant HER2 over wild-type EGFR.

FDA Indications

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain activating mutations (detected by an FDA-approved test) in adults who have received a prior systemic therapy — accelerated approval

Common Side Effects

• Diarrhea
• Rash
• Nausea
• Increased ALT
• Increased AST
• Increased lipase
• Decreased potassium
• Decreased sodium
• Decreased lymphocytes

Clinical Pearl

Sevabertinib is a second HER2 (ERBB2)-selective TKI for HER2 TKD-mutant NSCLC in the previously treated setting (dosed 20 mg twice daily with food). Beyond the shared HER2-TKI axes of diarrhea (start loperamide at the first loose stool), hepatotoxicity (LFTs at baseline, every 2 weeks for the first month, then monthly), and ILD/pneumonitis, it carries two distinctive monitoring requirements not shared with zongertinib: routine ocular-toxicity surveillance (prompt ophthalmology referral) and…

Related Therapies & Mechanisms

• Zongertinib (Hernexeos) — Tyrosine Kinase Inhibitor · NSCLC
• Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor · NSCLC
• Alectinib (Alecensa) — Tyrosine Kinase Inhibitor · NSCLC
• Capmatinib (Tabrecta) — Tyrosine Kinase Inhibitor · NSCLC