A Phase I Clinical Trial of MUC1-targeted CAR-T Cells with PD1 Nanobody MSLN Dual-target for Advanced Gynecological Solid Tumors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Screening patients who meet the criteria for peripheral blood mononuclear cell (PBMC) isolation and cell preparation. Based on the status of cell preparation and mutual agreement between the researcher and the participant, the date of reinfusion (Day 0) is determined. From Day -5 to Day -3, the participant receives a conditioning regimen with cyclophosphamide and antithymocyte globulin. After recovery for two days (Day -2 and Day -1), on Day 0, the participant receives reinfusion of BZE2203 (dose determined according to the dose-escalation requirements). The safety observation period lasts for 28 days, and clinical efficacy is assessed from Day 28 to Day 34. After comprehensive judgment, the second course of cell therapy is selected. Follow-up observations and evaluations are conducted once every three months, with follow-up visits once a year and telephone follow-ups once every two months.
详细描述
This study is a single-arm, open-label, dose-escalation and expansion clinical trial. The study is divided into two phases: the dose-escalation phase and the dose-expansion phase.
The dose-escalation phase is designed with three predefined dose levels, following a "3+3 design" and progressing from low to high doses. The "3+3" dose-escalation scheme is as follows: if no dose-limiting toxicity (DLT) occurs in the three subjects at a given dose level during the observation period, the dose will be escalated to the next higher level. If one subject out of the initial three experiences DLT at a dose level, an additional three subjects will be enrolled at that dose level for further DLT observation. The dose level at which no more than one subject out of the final six subjects experiences DLT will be defined as the maximum tolerated dose (MTD).
The dose level for the expansion phase will be determined based on a comprehensive consideration of the occurrence of DLT and the efficacy results obtained, with the actual occurrence serving as the basis.
The safety of CAR-T therapy will be assessed by monitoring adverse events (AE) following cell therapy. The efficacy of CAR-T therapy will be evaluated by observing disease response following cell therapy. Blood samples will be collected before cell infusion and within one year after infusion to measure the number of CAR-T cells, CAR copy number, and PD-1 nanobody concentration, thereby evaluating the pharmacokinetics of CAR-T cells. Blood samples will also be collected before cell infusion and within 28 days after infusion to measure the concentrations of relevant cytokines, in order to assess the pharmacodynamic characteristics of CAR-T therapy.
During the study, blood samples used for the production of CAR-T cells will be transported to Shanghai Cell Therapy Group Pharmaceutical Technology Co., Ltd. After the production of CAR-T cells is completed, the cells will be shipped to the study sponsor, who will then infuse the CAR-T cells into the corresponding subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cell therapy group
Screening patients who meet the criteria for peripheral blood mononuclear cell (PBMC) isolation and cell preparation. Based on the cell preparation status and mutual agreement between the researcher and the participant, the date of reinfusion (Day 0) is determined. On Days -5 to -3, the participant receives a conditioning regimen with cyclophosphamide and antithymocyte globulin. After recovery for two days (Days -2 and -1), on Day 0, the participant receives reinfusion of BZE2203 (dose determined according to the dose-escalation requirements). The safety observation period lasts for 28 days, and clinical efficacy is evaluated from Day 28 to Day 34. After comprehensive judgment, the second course of cell therapy is selected. Follow-up observations and evaluations are conducted once every three months, with follow-up visits once a year and telephone follow-ups once every two months.
干预措施: Cell therapy with bispecific antibodies (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: The time frame was from subject enrollment until one year after the treatment
次要结局
未报告次要终点