Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: a drug evaluation of phase I and II data.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Misako Nagasaka, Danielle Brazel, Sai-Hong Ignatius Ou
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引用次数: 0

Abstract

Introduction: While crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC), unmet needs remain. These unmet needs include treatment options for patients with resistance mutations and efficacious options even in the presence of brain metastasis while simultaneously avoiding unwanted neurological side effects.

Areas covered: Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address central nervous system penetration while conferring fewer neurological adverse events. All of these features are demonstrated and supported by data from the phase I and the regional phase II TRUST-I clinical trial. Here, we describe the preclinical and clinical characteristics of taletrectinib and evaluate the data from phase I and II studies and review the rationale and design of TRUST-II, a global phase II study of taletrectinib, which is enrolling patients in North America, Europe, and Asia.

Expert opinion: Taltrectinib has the potential to improve PFS based on its greater potency against ROS1+ tumors and high CNS penetration. By selectively inhibiting ROS1 wild-type and its resistant mutations over TRKB, taltrectinib has a better safety profile with minimal CNS-related AEs compared to other ROS1+ inhibitors.

治疗 ROS-1 阳性非小细胞肺癌的 Taletrectinib:对 I 期和 II 期数据的药物评估。
简介虽然克唑替尼和恩替替尼已被批准用于治疗ROS1融合阳性(ROS1+)非小细胞肺癌(NSCLC),但仍有未满足的需求。这些未满足的需求包括耐药突变患者的治疗方案,以及即使出现脑转移也能有效治疗的方案,同时避免不必要的神经系统副作用:Taletrectinib旨在:提高疗效;克服对第一代ROS1抑制剂的耐药性;解决中枢神经系统渗透问题,同时减少神经系统不良反应。所有这些特点都得到了 I 期和地区 II 期 TRUST-I 临床试验数据的证明和支持。在此,我们描述了taletrectinib的临床前和临床特点,评估了I期和II期研究的数据,并回顾了TRUST-II的原理和设计,TRUST-II是taletrectinib的一项全球性II期研究,目前正在北美、欧洲和亚洲招募患者:Taltrectinib对ROS1+肿瘤有更强的抑制作用,且具有较高的中枢神经系统穿透力,因此有可能改善PFS。通过选择性抑制ROS1野生型及其耐药突变而非TRKB,与其他ROS1+抑制剂相比,taltrectinib具有更好的安全性,中枢神经系统相关的AEs极少。
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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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