A Phase I Clinical Study to Evaluate the Safety and Efficacy of IM96 CAR-T Cell Injection in Advanced Adenocarcinoma of Gastric/Esophagogastric Junction
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- Beijing Immunochina Medical Science & Technology Co., Ltd.
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Incidence of Treatment Related adverse events (AEs)
概览
简要总结
This study, a single-center, open, single-dose clinical study, was designed to evaluate the safety and efficacy of IM96 CAR-T cells in treating patients with advanced adenocarcinoma of gastric/esophagogastric junction
详细描述
This study is planned to enroll 18-24 patients with advanced adenocarcinoma of gastric/esophagogastric junction,using a modified "3+3" design for dose escalation, with 3 dose groups of 6×10^8 CAR-T cells ,12×10^8 CAR-T cells and 20×10^8 CAR-T cells. 3-6 subjects are planned to be enrolled in each dose group to assess their safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in one dose group, the next dose group can be started. If the incidence of horizontal dose-limiting toxicity (DLT) in a dose group is ≤1/6 within 28 days after transfusion, transfusion of cells from the next dose group can be initiated.
This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The age is 18 to 75 years (including boundary values) and the gender is not limited;
- •Patients with advanced locally inoperable or metastatic adenocarcinoma of the stomach/gastric esophageal junction diagnosed by pathohistology;
- •Patients with metastatic stomach/gastric esophageal junction who have failed or are intolerant to standard therapy;
- •The standardized systemic treatment received by the patient must be in accordance with the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Gastric Cancer, 2025 Edition;
- •The standard prior treatment regimen should incorporate therapeutic strategies guided by relevant molecular biomarkers. Specifically, patients with HER2-positive tumors must have received HER2-targeted therapy;
- •Claims of treatment intolerance: Patients who are unable to continue current effective systemic standardized treatment due to toxic side effects such as grade ≥3 vomiting, diarrhea, abdominal pain, bone marrow suppression, etc., and who do not accept refusal for financial and personal reasons;
- •Presence of at least one measurable lesion that meets RECIST 1.1 criteria;
- •Patients must provide a tumor sample within 2 years that meets the requirements (paraffin block or number of unstained sections that meet the testing requirements set by the Institute) that is positive for GUCY2C expression by immunohistochemistry;
- •Eastern cooperative oncology group (ECOG) score of 0-1;
- •Women of childbearing potential who have a negative blood pregnancy test prior to the start of the trial and who agree to use effective contraception during the trial and up to the last follow-up visit;male patients whose partners are of childbearing potential agree to use effective contraception during the trial and up to the last follow-up visit;
排除标准
- •Presence of brain metastases;
- •Patients who have previously received or are awaiting an organ transplant;
- •Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);
- •Plasmapheresis (e.g., pleural effusion, abdominal effusion, pericardial effusion) with symptoms of compression that cannot be controlled with treatment;
- •Autoimmune disease requiring systemic immunosuppressive therapy (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) within 2 years prior to the start of screening;
- •Lung diseases that the inversgaters determined were not suitable for inclusion in the study;
- •Use of any of the following medications or treatments during the designated time period prior to cell collection:
- •Therapeutic doses of corticosteroids have been used within 7 days prior to cell collection. However, topical and inhaled steroids are permitted;
- •Received chemotherapeutic agents within 1 week prior to cell collection. Enrollment was allowed if the oral chemotherapeutic drug had passed at least 3 half-lives prior to cell collection;
- •Those who used drugs to stimulate bone marrow hematopoietic cell production within 5 days prior to cell collection;
研究组 & 干预措施
IM96 CAR-T Cells
After preconditioning with chemotherapy, IM96 CAR-T Cells will be evaluated
干预措施: IM96 CAR-T Cells (Biological)
结局指标
主要结局
Incidence of Treatment Related adverse events (AEs)
时间窗: Up to 28 days after CAR-T cell infusion
Incidence of adverse events associated with IM96 CAR-T cell infusion within 28 days of IM96 CAR-T cell infusion,type, frequency, and severity of abnormal clinically significant vital signs, electrocardiograms, and laboratory tests examined, including dose-limiting toxicity
次要结局
- Objective remission rate (ORR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Progression-free survival (PFS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Disease control rate (DCR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Duration of response (DOR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Overall survival (OS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- AUC (Area Under Curve) 0-D90(Up to 90 days after CAR-T cell infusion)
- Cmax (Peak Concentration)(Up to 28 days after CAR-T cell infusion)
- Tmax (Peak Time)(Up to 28 days after CAR-T cell infusion)
- Tumor markers CA19-9(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Tumor markers CEA(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)