NYU Melanoma SPORE

总体项目摘要 在过去十年中，免疫检查点抑制（ICI）疗法取得了令人印象深刻的临床成功， 与之相匹配的是临床上有用的工具的发展，以预测患者的反应和毒性。的 将患者结果和毒性的生物标志物整合到临床护理中将允许更优化的治疗 选择.纽约大学（NYU）黑色素瘤孢子的主要目标是解决 迫切需要开发和验证临床上有用的个性化生物标志物， 免疫检查点抑制疗法在辅助治疗中的应用。我们选择集中力量 在这一领域，因为FDA批准的免疫疗法在这一临床背景下已导致显着增加， 将这些治疗方法与辅助试验扩展到其他癌症。佐剂ICI的使用将 改变黑色素瘤和其他恶性肿瘤的免疫生物学。确定获益的生物标志物， 毒性是关键的，及时的，并有望具有广泛的适用性。我们所有的项目都被修改以反映这一点 调整重点，使整个计划的目标更具凝聚力，可实现性和影响力。 新生物标志物的开发需要分阶段进行。纽约大学黑色素瘤孢子包括项目 从靶点鉴定到临床相关性（项目1、2、3、4）， 到检测和临床验证（项目3，4），并最终临床实用性与测试在一个制药厂启动 临床试验（项目3）。纽约大学黑色素瘤孢子是特别适合实现这一目标，由于 我们广泛的患者基础和我们在生物标志物鉴定和开发方面的转化专业知识。医生 在纽约大学Langone Health（NYULH），每年治疗超过1,000名新的黑色素瘤患者。作为旗舰研究 NCI资助的纽约大学Perlmutter癌症中心（PCC）的黑色素瘤转化研究项目 在黑色素瘤生物标志物开发方面具有既定的合作记录和高影响力的发现， 来自纽约大学医学院3，800多名患者的丰富生物样本资源， 广泛的机构基础设施和能力将使纽约大学黑色素瘤孢子的特点， 用于黑素瘤患者临床管理的新型个性化生物标志物。这些的范围和可扩展性 资源将扩展到我们对2,700名黑色素瘤患者的研究，这些患者参加了III期多中心临床试验， 辅助设置（CheckMate 238、CheckMate 915和KEYNOTE 716）。纽约大学黑色素瘤孢子 PD/PI，Iman Osman和Jeffrey Weber博士，合并了黑色素瘤ICI药物的互补专业知识 开发、临床试验和生物标志物研究。我们将发挥我们的优势，解决紧迫的需求， 黑色素瘤领域，可以扩展到越来越多的ICI治疗癌症。

OVERALL PROJECT SUMMARY The impressive clinical successes in immune checkpoint inhibition (ICI) therapy over the last decade have not been matched by the development of clinically useful tools to predict patient response and toxicity. The integration of biomarkers of patient outcome and toxicity into clinical care would allow more optimal treatment selection. The primary objective of the New York University (NYU) Melanoma SPORE is to address the urgent need to develop and validate clinically useful, personalized biomarkers to optimally administer immune checkpoint inhibition therapies in the adjuvant setting. We have chosen to concentrate our efforts in this area because FDA approval of immunotherapies in this clinical context has led to a significant increase in the utilization of these treatments with expansion of adjuvant trials to other cancers. The use of adjuvant ICI will alter the immunobiology of melanoma and other malignancies as well. Identifying biomarkers of benefit and toxicity is critical, timely, and promises to have broad applicability. All of our projects were revised to reflect this adjusted focus, making the goals of the overall program more cohesive, achievable, and impactful. The development of new biomarkers requires a phased approach. The NYU Melanoma SPORE includes projects that span the biomarker development path from target identification and clinical relevance (Projects 1, 2, 3, 4), to assay and clinical validation (Projects 3, 4), and ultimately clinical utility with testing in an investigator-initiated clinical trial (Project 3). The NYU Melanoma SPORE is particularly well suited to achieve this objective due to our broad patient base and our translational expertise in biomarker identification and development. Physicians at NYU Langone Health (NYULH) treat over 1,000 new melanoma patients annually. As a flagship research program of the NCI-funded NYU Perlmutter Cancer Center (PCC), our melanoma translational research program has an established track record of collaboration and high impact findings in melanoma biomarker development, empowered by rich biospecimen resources from over 3,800 patients treated at NYULH These resources and extensive institutional infrastructure and capabilities will enable the NYU Melanoma SPORE to characterize novel personalized biomarkers for melanoma patient clinical management. The scope and scalability of these resources will extend to our studies of 2,700 melanoma patients enrolled in phase III, multisite clinical trials in the adjuvant setting (CheckMate 238, CheckMate 915 and KEYNOTE 716). The NYU Melanoma SPORE PD/PIs, Drs. Iman Osman and Jeffrey Weber, merge complementary expertise in melanoma ICI drug development, clinical trials, and biomarker investigations. We will apply our strengths to solve pressing needs in the melanoma field which which can be extended to the increasing number of ICI--treated cancers.