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Drugs. 2020 Jul;80(11):1133-1138. doi: 10.1007/s40265-020-01348-2.
Ripretinib (QINLOCK™) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST). Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF. In May 2020, oral ripretinib received its first approval in the USA for the treatment of adult patients with advanced GIST who have received prior treatment with ≥ 3 kinase inhibitors, including imatinib. The US FDA, Health Canada and the Australian Therapeutic Goods Administration collaborated on the review of the ripretinib new drug application in this indication as part of Project Orbis; regulatory review in Australia and Canada is ongoing. Clinical development for GIST, solid tumours and systemic mastocytosis is underway in several countries worldwide. This article summarizes the milestones in the development of ripretinib leading to this first approval for the treatment of advanced GIST.
瑞普替尼（QINLOCK）是一种新型的 II 型酪氨酸开关控制抑制剂，由 Deciphera Pharmaceuticals 开发用于治疗 KIT 原癌基因受体酪氨酸激酶（KIT）驱动和/或血小板衍生生长因子受体 A（PDGFRA）驱动的癌症，包括胃肠道间质瘤（GIST）。瑞普替尼抑制 KIT 和 PDGFRA 激酶，包括野生型、原发性和继发性突变，以及其他激酶，如 PDGFRB、TIE2、VEGFR2 和 BRAF。2020 年 5 月，口服瑞普替尼在美国首次获批用于治疗先前接受过至少 3 种激酶抑制剂（包括伊马替尼）治疗的晚期 GIST 成人患者。美国 FDA、加拿大卫生部和澳大利亚治疗用品管理局作为 Project Orbis 的一部分合作审查了 ripretinib 在这一适应症的新药申请；在澳大利亚和加拿大的监管审查正在进行中。瑞普替尼在全球多个国家正在进行 GIST、实体瘤和系统性肥大细胞增多症的临床开发。本文总结了导致 ripretinib 首次获批用于治疗晚期 GIST 的开发里程碑。
