Cancer Immunotherapy Trials Network Central Operations and Statistical Center

项目摘要 癌症免疫治疗试验网络（CITN）来自2007年NCI的讨论 免疫治疗剂研讨会，其中确定了高优先级药物，这些药物显示出 对癌症患者有益，但尚未广泛用于促癌剂启动的试验（IIT）。以来 2007年，由于抗PD1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抗体。然而，在NCI研讨会上确定的大多数优先代理人仍然没有广泛地 可用于学术IIT。 自2011年最初获奖以来，CITN专注于测试这些高优先级代理，其中包括5个顶级代理 8个排名的代理人击中目标的关键最佳免疫反应。CITN试验是为数不多的 这些药物的IIT，每个试验都有明确的生物学和治疗原则。两次审判导致 临床实践的变化。CITN的具体目标简述如下： 目标1：（a）继续开展针对成人癌症的创新性早期多中心免疫治疗试验 （B）成立儿科CITN（PedCITN）， 使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）为这些临床试验的进行提供领导、基础设施和统计支持; (d)继续获得对免疫反应至关重要且IIT无法广泛获得的高优先级药物 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、生物标志物认证） CITN的科学目标 1.继续试验与T细胞和自然杀伤细胞激活剂和生长因子IL-15，稳态T细胞生长 因子IL-7、树突状细胞活化剂抗CD40、树突状细胞生长因子Flt3L和IDO抑制剂±抗PD1 2.继续进行抗PD1治疗孤儿和超孤儿适应症（包括儿科癌症）的试验 3.进行活检密集试验，以确定抗PD1失败的可行原因，并与治疗相关 潜在补救剂的给药 4.进行试验以评估消除或激活骨髓、单核细胞/巨噬细胞和/或 存在于大多数癌症中的骨髓源性抑制细胞 5.针对儿童癌症患者开展多中心I期和早期II期免疫治疗试验 这些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，并可能改变标准实践或刺激 NCI合作团体和行业针对成人和儿童癌症的确证性关键试验。

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.