Melanoma and Skin Cancer Program SPORE

黑色素瘤和皮肤癌计划 SPORE

• 批准号: 10270227
• 负责人: John Munn Kirkwood
• 金额: $ 203.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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/10270227
• 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; Immune; 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; 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

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（CSCC）。尽管取得了长足的进展，大多数患有晚期黑色素瘤的患者并未受益 治疗，虽然黑色素瘤最有效的疗法也会引起严重的不良事件。此外，我们仍然 在免疫能力和免疫缺陷的患者中需要安全，高效和具有成本效益的疗法 这可以改变这些高危患者人群的治疗和结果。总体目标 黑色素瘤和皮肤癌计划（MSCP孢子）是为了克服新颖的翻译研究 当前黑色素瘤和CSCC疗法的障碍。这三个项目中的每个项目都来自半决赛和 MSCP孢子的调查员提出的创新发现，这些发现被翻译成新的 黑色素瘤和皮肤癌患者的组合免疫疗法试验。项目1将评估 抗LAG3的临床和免疫学活性单独并与抗PD1结合，首次在 没有接受过事先ICB的未接受治疗的国会议员。项目2将评估效率和免疫原性 在II/III期的情况下 肿瘤内CMP和Nivolumab（CMP/Nivo）与Nivo的随机临床试验。项目3将测试小说 微针阵列（MNA）装置，以提供有效的化学治疗剂以诱导免疫原性细胞 死亡和天生的免疫兴奋剂进入可访问的CSCC。这种方法将在 免疫能力和免疫抑制的癌症患者。MSCP孢子将使用创新策略 确定对拟议疗法的反应和抗性的机制。调查人员将是 在共享实用性核心的支持下，在1）样本中提供最先进的专业知识和规模 收集和处理，翻译病理学，数据注释，生物循环库以及 免疫调节器（核心1）; 2）生物统计学和生物信息学（核心2），支持严谨和 所有研究项目的可重复性。职业增强计划（CEP）和发展 研究计划（DRP）将吸引有才华的基本，翻译和临床研究人员进入黑色素瘤 研究。 MSCP孢子利用希尔曼癌症中心（HCC）资源和机构承诺 借助最先进的研究和临床设施，临床监管服务以支持临床试验 协调和翻译研究。 MSCP孢子包括出色的外部和内部 咨询委员会（EAB，IAB），执行委员会，在成功方面经验丰富 孢子和患者拥护者的管理。 MSCP孢子的组织结构将 彻底促进每个项目的进度和管理潜在障碍的管理。 MSCP孢子 将与科学界和其他孢子共享与NIH政策一致的数据。 MSCP 孢子将从学术中受益并促进大量的水平和垂直合作 机构，NCI，制药公司和合作组织。