Melanoma and Skin Cancer Program SPORE

项目摘要摘要：总体 皮肤癌是美国最常见的癌症，包括黑色素瘤和皮肤鳞状细胞癌。 癌（cSCC）。尽管取得了实质性进展，但大多数晚期黑色素瘤患者并没有从 黑色素瘤的最有效的治疗方法也会导致严重的不良事件。此外，我们还 在免疫功能正常和免疫缺陷患者中需要安全、有效和具有成本效益的cSCC治疗 这可能会改变这些高危患者群体的治疗和结果。的总体目标 黑色素瘤和皮肤癌计划（MSCP SPORE）旨在开发新型转化研究，以克服 目前黑色素瘤和cSCC治疗的障碍。三个项目中的每一个都是开创性的， MSCP SPORE调查人员的创新发现，这些发现被转化为新的 黑色素瘤和皮肤癌患者的联合免疫治疗试验。项目1将评估 抗LAG 3单独和与抗PD 1联合的临床和免疫活性，首次在 既往未接受过ICB的初治MP。项目2将评价疗效和免疫原性 CMP-001（CMP），一种A型CpG，在PD 1初治转移性黑色素瘤中的II/III期背景下 肿瘤内CMP和nivolumab（CMP/nivo）对比nivo的随机临床试验。项目3将测试一部小说 微针阵列（MNA）装置递送有效的化疗剂以诱导免疫原性细胞 死亡和先天免疫刺激剂进入可接近的cSCC。这种方法将在以下两个方面得到检验： 免疫功能正常和免疫抑制的癌症患者。MSCP SPORE将使用创新策略 以确定对所提出的疗法的反应和抗性的机制。调查人员将 在共享设施核心的支持下，提供最先进的专业知识和规模经济1）示例 收集和处理，转化病理学，数据注释，生物标本库，以及 免疫监测（核心1）;和2）生物统计学和生物信息学（核心2），支持严谨性和 所有研究项目的可重复性。职业提升计划（CEP）和发展 研究计划（DRP）将吸引有才华的基础，翻译和临床研究人员进入黑色素瘤 research. MSCP SPORE利用希尔曼癌症中心（HCC）的资源和机构承诺 拥有最先进的研究和临床设施，支持临床试验的临床监管服务 协调和翻译研究。MSCP SPORE包括未完成的外部和内部 咨询委员会（EAB，IAB），一个在成功的 SPORE和患者倡导者的管理。MSCP SPORE的组织结构将 促进对每个项目的进度和潜在障碍的管理的彻底跟踪。关于MSCP SPORE 将与科学界和其他符合NIH政策的SPORE共享数据。MSCP SPORE将受益于并促进与学术界的大量横向和纵向合作， 机构、NCI、制药公司和合作团体。

Project Summary Abstract: Overall Skin cancers are the most common cancers in the US, including melanoma and cutaneous squamous cell carcinoma (cSCC). Despite substantial progress, most patients with advanced melanoma do not benefit from treatment, while the most potent therapies of melanoma also cause serious adverse events. In addition, we still need safe, efficient, and cost-effective therapies of cSCCs in immunocompetent and immunodeficient patients that could transform treatment and outcomes for these at-risk patient populations. The overall goal of the Melanoma and Skin Cancer Program (MSCP SPORE) is to develop novel translational research to overcome the hurdles of current therapies of melanoma and cSCCs. Each of the three Projects results from seminal and innovative findings made by the investigators of the MSCP SPORE, which are translated into new combinatorial immunotherapy trials for patients with melanoma and skin cancers. Project 1 will assess the clinical and immunological activity of anti-LAG3 alone and in combination with anti-PD1, for the first time, in treatment-naïve MPs who have not received prior ICB. Project 2 will evaluate the efficacy, and immunogenicity of CMP-001 (CMP), a type A CpG, in PD1 naïve metastatic melanoma in the context of a phase II/III randomized clinical trial with intratumoral CMP and nivolumab (CMP/nivo) vs. nivo. Project 3 will test a novel microneedle array (MNA) device to deliver both a potent chemotherapeutic agent to induce immunogenic cell death and an innate immune stimulant into accessible cSCCs. This approach will be tested both in immunocompetent and immunosuppressed cancer patients.The MSCP SPORE will use innovative strategies to determine the mechanisms of response and resistance to the proposed therapies. The investigators will be supported by shared-facility cores to provide state-of-the-art expertise and economies-of-scale in 1) sample collection and processing, translational pathology, data annotation, biospecimen repository, and immunomonitoring (Core 1); and 2) biostatistics and bioinformatics (Core 2), supporting rigor and reproducibility across all research projects. The Career Enhancement Program (CEP) and Development Research Program (DRP) will attract talented basic, translational, and clinical investigators into melanoma research. The MSCP SPORE leverages Hillman Cancer center (HCC) resources and institutional commitment with state-of-the-art research and clinical facilities, clinical regulatory services to support clinical trial coordination, and translational research. The MSCP SPORE includes outstanding External and Internal Advisory Boards (EAB, IAB), an Executive Committee that is highly experienced in the successful management of SPOREs and Patient Advocates. The organizational structure of the MSCP SPORE will facilitate thorough following of progress and managing of potential hurdles for each project. The MSCP SPORE will share data with the scientific community and other SPOREs in agreement with the NIH policy. The MSCP SPORE will benefit from and promote a large number of horizontal and vertical collaborations with academic institutions, NCI, pharmaceutical companies, and cooperative groups.