Melanoma and Skin Cancer Program SPORE

黑色素瘤和皮肤癌计划 SPORE

基本信息

批准号：
10469631
负责人：
John Munn Kirkwood
金额：
$ 207.02万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10469631
关键词：
Advocate Agreement Award Basic Science Bioinformatics Biological Specimen Banks Biometry Cancer Biology Cancer Center Cancer Patient Cell Death Clinical Clinical Investigator Clinical Research Clinical Trials Collaborations Combination immunotherapy Communities Core Facility Cutaneous Cutaneous Melanoma Data Development Devices Fostering Goals Head and Neck Cancer Immunocompetent Immunologic Monitoring Immunologics Immunotherapy Institution Legal patent Lung Malignant Neoplasms Metastatic Melanoma Multi-Institutional Clinical Trial Nivolumab Ovarian Pathology Patient-Focused Outcomes Patients Pharmacologic Substance Phase Policies Program Development Randomized Clinical Trials Reproducibility Research Research Personnel Research Project Grants Research Support Resistance Resource Sharing Resources Risk Science Seminal Serious Adverse Event Services Skin Cancer Sum Talents Testing Time Translating Translational Research Treatment outcome United States National Institutes of Health Universities anti-PD-1 cancer cell cancer therapy career chemotherapeutic agent clinical efficacy combinatorial cost effective treatment data sharing efficacy evaluation experience immune stimulant immunogenic cell death immunogenicity immunosuppressed immunotherapy trials improved improved outcome in vivo imaging innovation interdisciplinary approach melanoma member novel novel strategies organizational structure patient population programmed cell death protein 1 programs research and development response sample collection skin squamous cell carcinoma success translational cancer research translational scientist tumor immunology

项目摘要

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.

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尽管取得了实质性进展，但大多数晚期黑色素瘤患者并未受益。治疗，而最有效的黑色素瘤疗法也会引起严重的不良事件。需要对免疫功能正常和免疫缺陷患者进行安全、有效且经济有效的 cSCC 治疗这可以改变这些高危患者群体的治疗和结果。黑色素瘤和皮肤癌计划 (MSCP SPORE) 将开发新颖的转化研究来克服当前黑色素瘤和鳞状细胞癌治疗的障碍来自于开创性和前瞻性的研究。 MSCP SPORE 的研究人员取得的创新发现被转化为新的项目 1 将评估黑色素瘤和皮肤癌患者的组合免疫治疗试验。单独使用抗 LAG3 以及与抗 PD1 联合使用的临床和免疫学活性，首次在之前未接受过 ICB 项目 2 的初治议员将评估疗效和免疫原性。 CMP-001 (CMP)（一种 A 型 CpG）在 II/III 期 PD1 幼稚转移性黑色素瘤中的应用肿瘤内 CMP 和 nivolumab (CMP/nivo) 与 nivo 的随机临床试验项目 3 将测试一种新型药物。微针阵列 (MNA) 装置可输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触及的 cSCC 将在这两种方法中进行测试。免疫功能健全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耐药机制。由共享设施核心支持，在 1) 样本中提供最先进的专业知识和规模经济收集和处理、转化病理学、数据注释、生物样本存储库以及免疫监测（核心 1）；2）生物统计学和生物信息学（核心 2），支持 ligor 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、转化和临床研究人员研究黑色素瘤 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 MSCP SPORE 包括出色的外部和内部研究。顾问委员会（EAB、IAB）是一个在成功的执行委员会中拥有丰富经验的执行委员会 SPORE 和患者倡导者的管理 MSCP SPORE 的组织结构将促进彻底跟踪每个项目的进展并管理潜在障碍。将根据 NIH 政策与科学界和其他 SPORE 共享数据。 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、合作团体。