背景:自2017年以来,下一代测序(NGS)已被引入许多韩国机构,以支持癌症的分子诊断,当时它有资格获得国民健康保险服务的报销。然而,基于NGS结果的分子指导治疗(MGT)的吸收受到限制,因为有关批准适应症之外的处方的严格规定,缺乏临床试验机会,以及大多数机构对分子肿瘤委员会(MTB)的访问权限有限。KOSMOS-II研究旨在证明MGT的可行性和有效性,由MTB通知,使用全国精准医疗平台。
方法:KOSMOS-II试验是一项大规模的全国性主观察性研究。它涉及一个框架,用于根据局部NGS测试筛选转移性实体瘤患者的可行遗传改变。它建议MGT通过每两周举行一次远程和集中的MTB会议。MGT可以包括以下选项之一:Tier1,针对ALK等遗传改变的研究药物的治疗用途,EGFR,ERBB2,BRAF,FH,ROS1和RET,或具有高肿瘤突变负担的药物;第2级,包括具有批准适应症的药物或韩国健康保险审查和评估服务批准的适应症之外的允许治疗的药物;第3级,涉及与MTB推荐的遗传改变相匹配的临床试验。考虑到接受MGT的患者的预期比例在50%±3.25%的范围内,这项研究旨在招募1,000名患者.患者必须已经进展到一个或多个治疗线并且在登记之前经历NGS。
结论:这个实用的主协议为罕见的遗传改变和高质量的真实世界数据提供了一个大规模筛查平台。附属临床试验,翻译研究,和临床基因组数据库将有助于为药物重新定位和开发新的生物标志物提供证据。
背景:NCT05525858。
BACKGROUND: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform.
METHODS: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment.
CONCLUSIONS: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers.
BACKGROUND: NCT05525858.