Cancer Immunotherapy Trials Network Central Operations and Statistical Center

项目摘要 癌症免疫治疗试验网络(CITN)是在2007年NCI的讨论中产生的 免疫治疗试剂研讨会，其中确定了高优先级的药物，显示出潜在的 使癌症患者受益--但这尚未广泛用于研究人员发起的试验(IITs)。自.以来 2007年，由于抗PD1抗体的成功，癌症免疫治疗领域发生了翻天覆地的变化 和抗PD-L1。然而，在NCI研讨会中确定的大多数优先代理仍然没有广泛地 适用于理工学院学生。 自2011年首次获奖以来，CITN专注于测试这些高优先级的代理，包括5个排名靠前的代理 8种排名靠前的药物，它们击中了对最佳免疫反应至关重要的目标。CITN试验是为数不多的学术试验之一 这些药物的IITS，每个试验都定义了生物和治疗原则。两次审判导致了 临床实践中的变化。创新及科技网的具体目标简略如下： 目标1：(A)继续进行成人癌症的创新早期多中心免疫疗法试验 使用高优先级免疫调节剂；(B)组建儿科CITN(PedCITN)进行创新 应用高优先级免疫调节剂治疗儿童癌症的早期多中心免疫治疗试验 (C)为进行这些临床试验提供领导、基础设施和统计支持； (D)继续获得对免疫反应至关重要、但不能广泛用于研究所的高优先级药物 目标2：与癌症免疫监测和分析中心(CIMAC)和其他实验室协调研究 CITN试验中成人和儿童患者的标本分析(免疫监测、生物标记物认证) CITN的科学目标 1.继续T细胞和自然杀伤细胞激活剂和生长因子IL-15的试验，平衡T细胞的生长 IL-7因子、树突状细胞激活剂抗CD40、树突状细胞生长因子Flt3L和IDO抑制因子±抗PD1 2.继续使用抗PD1进行孤儿和超孤儿适应症的试验，包括儿童癌症 3.进行活检密集试验，以确定抗PD1失败的可行原因，并与治疗有关 潜在救援人员的管理 4.进行试验以评估消除或激活髓系细胞、单核/巨噬细胞和/或 大多数癌症中存在的髓系来源的抑制细胞 5.对儿童癌症患者进行多中心I期和早期II期免疫治疗试验 这一结果将为未来的试验设计提供信息，并提高对这些高优先级药物的理解。CITN 试验旨在确定获得监管批准的途径，并可能改变标准做法或刺激 NCI合作组织和产业界针对成人和儿童癌症的验证性关键试验。

Project Summary The Cancer Immunotherapy Trials Network (CITN) came about from discussions at the 2007 NCI Immunotherapy Agent Workshop, in which high-priority agents were identified that showed the potential to benefit patients with cancer—but that were not yet broadly available for investigator-initiated trials (IITs). Since 2007, a sea change has occurred in the field of cancer immunotherapy, resulting from the success of anti-PD1 and anti-PD-L1. However, most of the priority agents identified in the NCI Workshop are still not broadly available for academic IITs. Since the original award in 2011, the CITN focused on testing these high-priority agents, including 5 of the top 8 ranked agents that hit targets critical for optimal immune responses. CITN trials are among the few academic IITs of these agents, and each trial has defined biologic and therapeutic principles. Two trials have led to changes in clinical practice. The abbreviated Specific Aims for the CITN are as follows: Aim 1: (a) to continue to conduct innovative early phase multicenter immunotherapy trials for adult cancers using high-priority immunomodulatory agents; (b) to form a Pediatric CITN (PedCITN) to conduct innovative early phase multicenter immunotherapy trials for pediatric cancers using high-priority immunomodulatory agents; (c) to provide leadership, infrastructure, and statistical support for the conduct of these clinical trials; (d) to continue to access high-priority agents central to immune responses and not broadly available for IITs Aim 2: to coordinate studies with Cancer Immune Monitoring and Analysis Center (CIMAC) and other labs for specimen analysis (immune monitoring, biomarker credentialing) of adult and pediatric patients on CITN trials Scientific Goals of the CITN 1. Continue trials with T cell and natural killer cell activator and growth factor IL-15, homeostatic T cell growth factor IL-7, dendritic cell activator anti-CD40, dendritic cell growth factor Flt3L, and IDO inhibitor ± anti-PD1 2. Continue trials with anti-PD1 for orphan and ultra-orphan indications, including pediatric cancers 3. Conduct biopsy-intense trials to identify actionable causes of anti-PD1 failure and linked to therapeutic administration of potential rescue agents 4. Conduct trials to assess therapies that eliminate or activate the myeloid, monocytes/macrophage, and/or myeloid-derived suppressor cells that reside within most cancers 5. Conduct multicenter Phase I and early Phase II immunotherapy trials for pediatric patients with cancer The results will inform future trial designs and improve the understanding of these high-priority agents. CITN trials are designed to identify paths to regulatory approval and will likely change standard practice or spur confirmatory pivotal trials by NCI cooperative groups and industry for adult and pediatric cancers.