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Phase 1/2 Clinical Study of Humanized Anti-BCMA CAR T Cells in Relapsed/Refractory Multiple Myeloma (MM)

人源化抗 BCMA CAR T 细胞治疗复发/难治性多发性骨髓瘤 (MM) 的 1/2 期临床研究

基本信息

批准号：
10010096
负责人：
Charles Andrew Stewart
金额：
$ 98.82万
依托单位：
CARTESIAN THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10010096
关键词：
Address Antibodies Antibody Response Antigen Targeting Antigens Autologous Autologous Stem Cell Transplantation B-Lymphocytes Biological Assay Biological Markers Blood Cell Maturation Cell Therapy Cellular immunotherapy Clinical Clinical Research Clinical Trials Clinical Trials Design Competence Cyclic GMP Cyclophosphamide DNA Data Development Diagnosis Differentiation Antigens Disease Dose Dose-Limiting Drug Kinetics European Evaluation Generations Goals Government Grant Half-Life Immunology Immunophenotyping In Vitro In complete remission Inflammatory Response Infusion procedures Malignant Neoplasms Maximum Tolerated Dose Measures Messenger RNA Molecular Biology Multiple Myeloma Patients Persons Phase Phase I Clinical Trials Phase I/II Clinical Trial Plasma Cells Population Pre-Clinical Model Process Production Proliferating Refractory Relapse Research Risk S Phase Safety Sensitivity and Specificity Serum Small Business Innovation Research Grant T memory cell T-Lymphocyte Testing Therapeutic Time Toxic effect advanced disease authority chimeric antigen receptor chimeric antigen receptor T cells clinical development curative treatments cytokine cytokine release syndrome cytotoxicity design experimental study first-in-human fludarabine immunogenicity improved in vivo innovation meetings neoplastic cell neurotoxicity next generation novel therapeutics operation preclinical development preconditioning relapse patients response safety assessment senescence treatment effect treatment response tumor virtual

项目摘要

ABSTRACT Multiple myeloma (MM) claims over 80,000 lives globally each year. Although several new therapies have been approved over the past decade, virtually all patients relapse, and the median survival remains at only 5 years. The depth of therapeutic response correlates with time to relapse, and eradicating tumor cells early in the disease process may be necessary to achieve clinical cure. A potentially curative approach is autologous cell therapy with chimeric antigen receptor (CAR) T-cells redirected to a target antigen. For MM, an attractive target antigen is B cell maturation antigen (BCMA), an antigen marker with extremely high sensitivity and specificity for myeloma and plasma cells. Experiments described in this SBIR proposal cover early-stage clinical research (Phase I/II Clinical Trial) of an autologous anti-BCMA CAR T-cell product generated with mRNA (Descartes-11) in order to overcome the toxicities associated with permanently modified CAR T-cells. The goals of the Specific Aims are to 1) determine the safety, tolerability and Maximum Tolerated Dose of Descartes-11 in patients with relapsed/refractory MM; 2) establish preliminary clinical benefit of Descartes-11 at MTD in relapsed/refractory MM; 3) define correlative biomarkers of safety and efficacy in Descartes-11-treated patients. Use of mRNA to generate Descartes-11 enables predictable pharmacokinetics, providing the prospect of controlled CAR T-cell treatment of MM early in the course of the disease.

摘要多发性骨髓瘤（MM）每年在全球夺去超过80，000人的生命。虽然有几种新的治疗方法在过去的十年中，几乎所有的患者都复发了，中位生存期仅为5年。治疗反应的深度与复发时间以及在疾病早期根除肿瘤细胞相关这可能是实现临床治愈所必需的。一种潜在的治疗方法是自体细胞疗法其中嵌合抗原受体（CAR）T细胞重定向至靶抗原。对于MM，有吸引力的靶抗原是B细胞成熟抗原（BCMA），一种对骨髓瘤和浆细胞。SBIR提案中描述的实验涵盖了早期临床研究用mRNA（Descartes-11）产生的自体抗BCMA CAR T细胞产物的I/II期临床试验以克服与永久修饰的CAR T细胞相关的毒性。具体目标目的是1）确定Descartes-11在患有以下疾病的患者中的安全性、耐受性和最大耐受剂量：复发性/难治性MM; 2）在复发性/难治性MM患者中确立MTD的Descartes-11的初步临床获益 MM; 3）定义Descartes-11治疗患者中安全性和疗效的相关生物标志物。使用mRNA 产生Descartes-11能够实现可预测的药代动力学，提供受控CAR T细胞的前景在疾病的早期治疗MM。