CD38-TARGETED IMMUNOPET OF MYELOMA: PHASE 2 TRIAL OF CLINICAL APPLICATIONS

CD38 靶向骨髓瘤免疫宠物：临床应用 2 期试验

• 批准号: 10756584
• 负责人: Carl Ola Landgren
• 金额: $ 5万
• 依托单位: HOAG MEMORIAL HOSPITAL PRESBYTERIAN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756584
• 关键词: Antibodies; Biopsy; Blood Tests; Bone marrow biopsy; Cells; Clinical; Clinical Trials; Combined Modality Therapy; Detection; Detection of Minimal Residual Disease; Disease; Funding Opportunities; Future; Goals; Histologic; Human; Image; ImmunoPET; Immunoglobulins; Investigation; Laboratories; Measurement; Measures; Membrane Proteins; Memorial Sloan-Kettering Cancer Center; Methods; Monitor; Monoclonal Antibodies; Multiple Myeloma; PET/CT scan; Patient Care; Patient Monitoring; Patient imaging; Patients; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Plasma Cell Neoplasm; Plasma Cells; Positron-Emission Tomography; Prognosis; Prognostic Marker; Protein Secretion; Qualifying; Radiochemistry; Radioimmunotherapy; Radiolabeled; Research Personnel; Residual Neoplasm; Safety; Selection for Treatments; Serum; Site; Surface; Therapeutic Agents; Tracer; Translations; Tumor Burden; United States; Visualization; Work; blind; burden of illness; cancer imaging; clinical application; clinical care; clinically significant; design; dosimetry; early phase trial; experience; first-in-human; fluorodeoxyglucose positron emission tomography; human imaging; imaging agent; imaging modality; individual patient; innovation; multiple myeloma M Protein; novel; phase I trial; phase II trial; preclinical imaging; predicting response; targeted imaging; theranostics; treatment response; tumor; uptake; virtual

Project Summary / Abstract Multiple myeloma is a plasma cell neoplasm with poor prognosis but promising future treatment. Current measurements of myeloma disease burden are suboptimal, and this limits clinical care. We have completed a first-in-human trial of CD38-targeted immunoPET with the radiolabeled anti-CD38 monoclonal antibody, 89Zr- DFO-daratumumab, which very successfully visualized myeloma disease burden as never done before. This proposal is a phase 2 clinical trial to identify clinically valuable applications of CD38-targeted immunoPET in patients with multiple myeloma. Our central hypothesis is that targeted imaging of CD38, which is expressed on the surface of virtually every myeloma cell, will allow clinically valuable non-invasive immuno-PET imaging of patients with myeloma. This would be a transformative strategy for the measurement of myeloma tumor burden, selection of therapeutic agents, and monitoring of treatment response. In the first aim of the study, we will determine the correlation between tumor uptake of 89Zr-DFO-daratumumab with clinically standard laboratory and imaging measurement of myeloma, including patient serum M protein concentration, percentage of plasma cells on bone marrow biopsy, FDG PET/CT, and whole-body MR. Because current approaches to assessing myeloma tumor burden are sub-optimal, developing a method to sensitively visualize and localize myeloma could have a profound impact on patient care. In the second aim of the study, we will determine if tumor uptake of 89Zr-DFO-daratumumab predicts response to daratumumab-containing combination therapy. Not all patients respond to daratumumab therapy; thus, a method of predicting response would be valuable for selection of therapy in individual patients. In the third aim, we will determine if 89Zr-DFO-daratumumab imaging following daratumumab-containing combination therapy can detect clinically significant residual disease. Detection of minimal residual disease (MRD) following therapy continues to grow in importance as a prognostic marker and endpoint in myeloma clinical trials. A method of visualizing and localizing residual disease would impact patient care, as well as enhance trials of developing myeloma therapies. The ultimate goal of this work would be the identification of clinically valuable applications for 89Zr-DFO- daratumumab immunoPET and, if successful, advancement toward FDA approval of this agent.

项目概要/摘要 多发性骨髓瘤是一种浆细胞肿瘤，预后较差，但未来治疗有希望。当前的 骨髓瘤疾病负担的测量结果并不理想，这限制了临床护理。我们已经完成了一个 使用放射性标记的抗 CD38 单克隆抗体 89Zr- 进行 CD38 靶向免疫 PET 的首次人体试验 DFO-daratumumab，非常成功地将骨髓瘤疾病负担可视化，这是以前从未做过的。这 该提案是一项 2 期临床试验，旨在确定 CD38 靶向免疫 PET 在以下领域的临床价值应用： 多发性骨髓瘤患者。 我们的中心假设是 CD38 的靶向成像，CD38 几乎表达于每个细胞的表面。 骨髓瘤细胞将允许对骨髓瘤患者进行具有临床价值的非侵入性免疫 PET 成像。这 将是测量骨髓瘤肿瘤负荷、选择治疗药物的变革性策略 剂，并监测治疗反应。 在该研究的第一个目标中，我们将确定肿瘤摄取 89Zr-DFO-daratumumab 之间的相关性 对骨髓瘤进行临床标准实验室和影像测量，包括患者血清 M 蛋白 浓度、骨髓活检中浆细胞的百分比、FDG PET/CT 和全身 MR。因为 目前评估骨髓瘤肿瘤负荷的方法并非最佳，因此需要开发一种敏感的方法 骨髓瘤的可视化和定位可能对患者护理产生深远影响。 在该研究的第二个目标中，我们将确定肿瘤摄取 89Zr-DFO-daratumumab 是否可以预测缓解 含达雷妥尤单抗的联合疗法。并非所有患者都对达雷妥尤单抗治疗有反应；因此，一个 预测反应的方法对于个体患者的治疗选择很有价值。 在第三个目标中，我们将确定含有 daratumumab 的 89Zr-DFO-daratumumab 成像是否有效 联合治疗可以检测临床上显着的残留疾病。微小残留病检测 治疗后（MRD）作为骨髓瘤的预后标志物和终点的重要性持续增长 临床试验。可视化和定位残留疾病的方法将影响患者护理以及 加强开发骨髓瘤疗法的试验。 这项工作的最终目标是确定 89Zr-DFO- 具有临床价值的应用。 daratumumabimmunoPET，如果成功，将进一步推动 FDA 批准该药物。