Adagrasib:首次批准。
Adagrasib: First Approval.
发表日期:2023 Feb
作者:
Sohita Dhillon
来源:
DRUGS
摘要:
Adagrasib(KRAZATI™)是Mirati Therapeutics研发的一种口服、高效、不可逆、小分子抑制剂,用于治疗患有KRAS G12C致癌驱动突变的实体瘤,包括非小细胞肺癌(NSCLC)和结直肠癌(CRC)。 Adagrasib可以共价结合到KRAS G12C突变体的半胱氨酸上,并将突变KRAS蛋白锁定在其不活跃状态中,从而阻止下游信号传导,而不影响野生型KRAS蛋白。2022年12月,Adagrasib在美国获得首次批准,用于治疗已接受≥1次系统治疗的KRAS G12C突变性局部晚期或转移性NSCLC成人(经由FDA批准的检测确定)。它基于客观反应率和反应持续时间获得了加速批准,并且对于这种适应症的持续批准可能取决于在确认试验中验证和描述的临床益处。该药物正在欧洲联盟进行NSCLC的监管审查,并在美国开发用于CRC。Adagrasib在包括CRC在内的固体肿瘤的临床研究正在多个国家进行。本文总结了Adagrasib的研发里程碑,以及其获得用于治疗KRAS G12C突变性局部晚期或转移性NSCLC的首次批准的过程。© 2023. 版权所有的作者,独家许可给Springer Nature Switzerland AG。
Adagrasib (KRAZATI™) is an orally available, potent, irreversible, small molecule inhibitor of KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of solid tumours harbouring KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Adagrasib covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state, thereby preventing downstream signalling without affecting wild-type KRAS protein. In December 2022, adagrasib received its first approval in the USA for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic NSCLC (as determined by an FDA approved test) who have received ≥ 1 prior systemic therapy. It was approved under accelerated approval based on objective response rate and duration of response, and its continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). The drug is under regulatory review for NSCLC in the European Union and is in development for CRC in the US. Clinical studies of adagrasib in solid tumours, including CRC, are underway in several countries. This article summarizes the milestones in the development of adagrasib leading to this first approval for KRAS G12C-mutated locally advanced or metastatic NSCLC.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.