Bladder Cancer Program

膀胱癌计划

基本信息

批准号：
10702537
负责人：
Andrea Apolo
金额：
$ 105.72万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10702537
关键词：
Adjuvant Study Area Cancer Etiology Cessation of life Clinical Cystectomy Disease High Prevalence Human IgG1 Immune checkpoint inhibitor Immunotherapy Ligands Malignant Neoplasms Malignant neoplasm of urinary bladder Modality Muscle PD-1/PD-L1 Pathway interactions Patients Phase III Clinical Trials Principal Investigator Randomized Reporting Research Somatic Mutation Testing Transitional Cell Carcinoma Treatment outcome Tumor-Infiltrating Lymphocytes United States United States Food and Drug Administration Urothelium Woman anti-PD-L1 bladder transitional cell carcinoma first-in-human high risk improved improved outcome inhibiting antibody men novel therapeutics pembrolizumab programmed cell death ligand 1 programmed cell death protein 1 programs response targeted agent treatment choice tumor tumor microenvironment

项目摘要

Immunotherapy with immune checkpoint inhibitors, particularly agents targeting the axis of programmed cell death protein 1 and its ligand (PD-1/PD-L1), has improved treatment outcomes in many tumor types. The rationale for assessing immune checkpoint inhibitors in advanced urothelial cancer is supported by a high prevalence of tumor somatic mutations and the presence of PD-L1 expression on tumors and tumor-infiltrating lymphocytes in the tumor microenvironment. Avelumab is a fully human anti-PD-L1 IgG1 antibody that inhibits PD-1/PD-L1 interactions but leaves the PD-1/PD-L2 pathway intact. The first-in-human trial of avelumab was led at the intramural NCI and I led the clinical effort for avelumab in advanced/metastatic urothelial carcinoma which showed clinical benefit, leading to approval by the U.S. Food and Drug Administration (FDA) for this indication. Given the activity of several immune checkpoint inhibitors in this setting, I was eager to test these agents in an earlier disease setting in patients with high-risk muscle-invasive disease. I initiated a phase 3 clinical trial of adjuvant pembrolizumab post-cystectomy in patients with high-risk muscle-invasive urothelial carcinoma of the bladder and upper tract. I am the principal investigator on this Alliance/NCI-sponsored study. The trial is accrued with 702 patients randomized. If positive, would provide a treatment choice for patients with urothelial carcinoma in this setting.

免疫检查点抑制剂的免疫疗法，尤其是针对程序性细胞死亡蛋白1及其配体（PD-1/PD-L1）轴的药物，已改善了许多肿瘤类型的治疗结果。肿瘤体突变的高患病率以及在肿瘤微环境中肿瘤和肿瘤浸润淋巴细胞上的PD-L1表达的高患病率支持，评估晚期尿路上皮癌中免疫检查点抑制剂的基本原理。 AVELUMAB是一种完全人类的抗PD-L1 IgG1抗体，可抑制PD-1/PD-L1相互作用，但使PD-1/PD-L2途径保持完整。 AVELUMAB的第一项人类试验在壁内NCI领导，我领导了Avelumab的临床临床努力，用于晚期/转移性尿路上皮癌，这显示了临床益处，从而获得了美国食品和药物管理局（FDA）的批准。鉴于在这种情况下的几种免疫检查点抑制剂的活性，我渴望在具有高风险肌肉侵入性疾病的患者的早期疾病环境中测试这些药物。我开始了辅助pembrolizumab后囊切除术的3阶段临床试验，该试验对膀胱和上大道的高风险肌肉炎性尿路上皮癌患者进行了3阶段试验。我是该联盟/NCI赞助的研究的主要研究员。该试验由702例随机分组。如果阳性，在这种情况下，将为尿路上皮癌患者提供治疗选择。