Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 106TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden.
背景/目的：MDG1011是一种针对HLA-A*02:01阳性患者的黑色素瘤优先表达抗原（PRAME）特异性自体T细胞受体（TCR）T细胞疗法。本文报告了首次人体（FIH）临床试验CD-TCR-001中关于MDG1011在复发/难治性（r/r）急性髓系白血病（AML）、骨髓增生异常综合征（MDS）和多发性骨髓瘤（MM）患者中的治疗可行性、安全性、耐受性和临床活性的数据。方法：在13名入组患者中，有9名接受了MDG1011治疗，剂量水平为每公斤体重0.1至5 × 10^6 TCR-T细胞。除临床评估外，还通过监测与细胞因子释放综合征（CRS）相关的细胞因子、MDG1011的存在与持续性以及PRAME mRNA水平的变化，在特定时间点评估安全性和潜在的生物活性。结果：治疗耐受性良好。未观察到剂量限制性毒性（DLTs），最常见的严重不良事件与淋巴细胞清除化疗和/或疾病进展相关。多项参数提示了MDG1011 TCR-T疗法的临床和生物活性迹象，包括两名患者出现可测量的临床反应、另外两名患者发生CRS，以及七名患者的骨髓（BM）或外周血（PB）中PRAME mRNA水平降低。结论：在CD-TCR-001试验第一阶段入组的少数患者中，观察到了MDG1011潜在的临床和生物活性迹象。r/r AML患者的疾病晚期阶段和快速进展限制了其临床影响。MDG1011可接受的安全性特征值得进一步研究该TCR-T疗法，可能适用于疾病早期阶段且肿瘤负荷较低的患者。
肿瘤(癌症)患者之家