Sevabertinib

Sevabertinib is indicated for the treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations. == Adverse effects ==

The US prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. == History ==

Efficacy was evaluated in people with unresectable or metastatic, non-squamous non-small cell lung cancer with HER2 (ERBB2) tyrosine kinase domain activating mutations who had received prior systemic therapy and received sevabertinib in SOHO-01 (NCT05099172), an open-label, single-arm, multi-center, multi-cohort clinical trial. HER2 (ERBB2) activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment. The US Food and Drug Administration granted the application for sevabertinib priority review, breakthrough therapy, and orphan drug designations. == Synthesis ==

The original route of synthesis of sevabertinib was disclosed in a patent filed by Bayer. The route is shown below: The route is convergent. The first structural fragment (Intermediate 2-1) is synthesized by the nucleophilic aromatic substitution of the nitrile and 1,4-dioxane-2-methanol in a basic condition, followed by hydrogenation catalyzed by Raney nickel. The synthesis of the other structural fragment (Intermediate 5-1) starts from a reaction of the amine with thiophosgene to form the isothiocyanate, followed by a condensation reaction with the protected β-carbonyl lactam and an acidic deprotection. The two intermediates go through further condensations to give racemic sevabertinib, which finally goes through a chiral resolution by preparative chiral HPLC to give the desired enantiomer. Alternatively, to save the chiral resolution in the end, sevabertinib can also be synthesized from a chiral starting material (2R)-1,4-dioxane-2-methanol in a likewise manner. == Society and culture ==

Legal status Sevabertinib was approved for medical use in the United States in November 2025. Names Sevabertinib is the international nonproprietary name. Sevabertinib is sold under the brand name Hyrnuo. == References ==