A Phase I Clinical Study of Cord Blood-Derived CAR-NK Cells Targeting Claudin18.2 in the Treatment of Advanced Gastric Cancer and Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- MTD
研究概览
简要总结
Main Objective: To study the maximum tolerated dose (MTD) and dose-dependent toxicity (DLT) of cord blood-derived CAR-NK cells (CB CAR-NK182) targeting Claudin18.2 in patients with advanced gastric cancer and advanced pancreatic cancer.
Secondary Objective: To evaluate the efficacy of CB CAR-NK182 in patients with advanced gastric cancer and advanced pancreatic cancer: overall objective tumor response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), etc.
To evaluate the CAR-NK amplification and persistence of CB CAR-NK182 in the blood of patients with advanced gastric cancer and advanced pancreatic cancer;
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
- •Male or female aged 18-75 years (inclusive);
- •Understands and voluntarily signs a written informed consent form, and is willing and able to comply with all trial requirements;
- •Patients with advanced gastric cancer and advanced pancreatic cancer confirmed by histopathology or cytology, who have failed standard treatment or cannot tolerate standard treatment, including but not limited to: pancreatic cancer and gastric cancer;
- •Immunohistochemical (IHC) detection of CLDN18.2, the positive expression of CLDN18.2 in tumors must be ≥ 10%;
- •At least 1 measurable lesion according to RECIST 1.1;
- •ECOG score is 0-1;
- •All toxic reactions caused by previous antineoplastic therapy were resolved to grade 0-1 (according to NCI CTCAE 5.0 edition); Expected survival ≥ 12 weeks;
- •In addition to the primary disease, no serious hematology, heart and lung, liver and kidney disease, laboratory tests meet the following requirements:
- •Peripheral blood neutrophil absolute value ≥ 2000/mm3, platelet ≥ 50000/mm3 Serum creatinine ≤ 1.5mg/dL;ALT (alanine aminotransferase)/AST (aspartate aminotransferase) below 2.5 times the upper limit of normal; Total bilirubin ≤ 1.5mg/dL; Cardiac ejection fraction (EF)≥ 50%; International standard ratio (INR) or prothrombin time (PT) below 1.5 times the upper limit of normal; Activated partial coagulation time (aPTT) below 1.5 times the upper limit of normal;
- •Women of childbearing potential must have a negative serum pregnancy test and agree to effective birth control during the treatment phase and within 12 months after injection of CAR-NK cells; Male patients must agree to use effective birth control during the study and for 12 months after injection of CAR-NK cells.
排除标准
- •History of other tumors;
- •Patients who have received CAR-T,CAR-NK,TCR-T and other cell therapy targeting Claudin18.2 within 3 months before study treatment;
- •Patients with hypersensitivity to cell therapy or any related drugs;
- •Active autoimmune diseases;
- •Active infections that cannot be controlled;
- •HIV infection, uncontrolled HBV, HCV and syphilis infections;
- •Have metastatic disease of the central nervous system (CNS), leptomeningeal disease or spinal cord compression;
- •Patients with severe heart disease;
- •Patients with unstable/active ulcers or bleeding from the digestive system;
- •Patients with a history of bleeding or bleeding tendency in the digestive system;
- •Pregnant or lactating women;
- •There are other factors that the researcher believes are not suitable for participating in the trial.
研究组 & 干预措施
CB CAR-NK182 Dose Escalation
Participants will receive a lymphodepleting conditioning regimen (FC regimen) followed by three intravenous infusions of Claudin18.2-targeted umbilical cord blood-derived CAR-NK cells (CB CAR-NK182) on days 0, 3, and 7. The study follows a "3+3" dose-escalation design with three planned dose levels.
Three dose levels: Dose Level 1 (2×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 2 (8×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 3 (16×10⁶ cells/kg/infusion on days 0, 3, and 7). 3-6 subjects will be enrolled per dose level. Each subject will be observed for at least 28 days after the first infusion, with a long-term follow-up period of 2 years post-first infusion.
Standard "3+3" rules apply for DLT observation and dose escalation decisions.
干预措施: CB CAR-NK18.2 (Biological)
CB CAR-NK182 Dose Escalation
Participants will receive a lymphodepleting conditioning regimen (FC regimen) followed by three intravenous infusions of Claudin18.2-targeted umbilical cord blood-derived CAR-NK cells (CB CAR-NK182) on days 0, 3, and 7. The study follows a "3+3" dose-escalation design with three planned dose levels.
Three dose levels: Dose Level 1 (2×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 2 (8×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 3 (16×10⁶ cells/kg/infusion on days 0, 3, and 7). 3-6 subjects will be enrolled per dose level. Each subject will be observed for at least 28 days after the first infusion, with a long-term follow-up period of 2 years post-first infusion.
Standard "3+3" rules apply for DLT observation and dose escalation decisions.
干预措施: Fludarabine (Drug)
CB CAR-NK182 Dose Escalation
Participants will receive a lymphodepleting conditioning regimen (FC regimen) followed by three intravenous infusions of Claudin18.2-targeted umbilical cord blood-derived CAR-NK cells (CB CAR-NK182) on days 0, 3, and 7. The study follows a "3+3" dose-escalation design with three planned dose levels.
Three dose levels: Dose Level 1 (2×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 2 (8×10⁶ cells/kg/infusion on days 0, 3, and 7), Dose Level 3 (16×10⁶ cells/kg/infusion on days 0, 3, and 7). 3-6 subjects will be enrolled per dose level. Each subject will be observed for at least 28 days after the first infusion, with a long-term follow-up period of 2 years post-first infusion.
Standard "3+3" rules apply for DLT observation and dose escalation decisions.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
MTD
时间窗: 1 month
Maximum Tolerated Dose
DLT
时间窗: 1 month
Dose-Dependent Toxicity
次要结局
- DCR(3 years)
- ORR(3 years)
- OS(3 years)
- DOR(3 years)
- PFS(3 years)
研究者
Liu Yang
MD
Zhejiang Provincial People's Hospital