Herbst Roy S, Gandara David R, Hirsch Fred R, Redman Mary W, LeBlanc Michael, Mack Philip C, Schwartz Lawrence H, Vokes Everett, Ramalingam Suresh S, Bradley Jeffrey D, Sparks Dana, Zhou Yang, Miwa Crystal, Miller Vincent A, Yelensky Roman, Li Yali, Allen Jeff D, Sigal Ellen V, Wholley David, Sigman Caroline C, Blumenthal Gideon M, Malik Shakun, Kelloff Gary J, Abrams Jeffrey S, Blanke Charles D, Papadimitrakopoulou Vassiliki A
Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.
University of California Davis Cancer Center, Sacramento, California.
Clin Cancer Res. 2015 Apr 1;21(7):1514-24. doi: 10.1158/1078-0432.CCR-13-3473. Epub 2015 Feb 13.
The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy "Master Protocol," using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.
肺癌主方案（Lung-MAP，S1400）是一项具有开创性的临床试验，旨在推动针对肺鳞状细胞癌（SCC）的靶向治疗的高效开发。尽管癌症基因组图谱项目及类似研究在肺SCC中检测到大量体细胞基因突变/扩增，其中一些可为研究性药物所靶向，但目前尚无针对晚期肺SCC的获批靶向治疗。然而，这些变化的频率较低（5%-20%），这使得在传统临床试验环境中招募患者和开展研究颇具挑战性。在此，我们描述了我们开发一种由生物标志物驱动的II期/II期多子研究“主方案”的方法，即使用一个通用平台（下一代DNA测序）来识别可采取行动的分子异常，然后随机分配接受相关靶向治疗或标准治疗。
