Tovorafenib (OJEMDA™) 是一种每周一次口服、选择性、脑渗透性 II 型 RAF 激酶抑制剂，由 Day One Biopharmaceuticals, Inc. 经武田肿瘤学 (Takeda Oncology) 许可开发，用于治疗儿科低级别神经胶质瘤 ( pLGG）和实体瘤。大多数 pLGG 的 MAPK 通路发生改变，例如 BRAF 突变或 BRAF 融合，从而导致异常的细胞内信号传导。 Tovorafenib 是突变型 BRAF V600E、野生型 BRAF 和野生型 CRAF 激酶以及 BRAF 融合体的抑制剂。 2024年4月，托沃拉非尼在美国首次获得批准，用于治疗年龄≥6个月、携带BRAF融合或重排或BRAF V600突变的复发或难治性pLGG患者。根据正在进行的关键 2 期 FIREFLY-1 研究中该人群所达到的缓解率和缓解持续时间，该适应症获得了加速批准。托沃拉非尼的临床开发正在全球许多国家进行。本文总结了托沃拉非尼开发过程中的里程碑，这些里程碑导致首次批准用于具有激活 BRAF 改变的复发或难治性 pLGG。© 2024。作者，获得 Springer Nature Switzerland AG 的独家许可。

Tovorafenib (OJEMDA™) is a once-weekly oral, selective, brain-penetrant, type II RAF kinase inhibitor being developed by Day One Biopharmaceuticals, Inc., under a license from Takeda Oncology, for the treatment of paediatric low-grade glioma (pLGG) and solid tumours. Most pLGGs harbour alterations in the MAPK pathway, such as a BRAF mutation or BRAF fusion, which result in aberrant intracellular signalling. Tovorafenib is an inhibitor of mutant BRAF V600E, wild-type BRAF and wild-type CRAF kinases and BRAF fusions. In April 2024, tovorafenib received its first approval in the USA for the treatment of patients aged ≥ 6 months with relapsed or refractory pLGGs harbouring a BRAF fusion or rearrangement, or BRAF V600 mutation. It received accelerated approval for this indication based on the response rate and duration of response achieved in this population in the ongoing, pivotal, phase 2 FIREFLY-1 study. Clinical development of tovorafenib is underway in numerous countries worldwide. This article summarizes the milestones in the development of tovorafenib leading to this first approval for relapsed or refractory pLGG with an activating BRAF alteration.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.