Exploratory Clinical Study of Combined Claudin18.2-Targeted CAR-DC and CAR-T Therapy in Patients With Advanced Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Safety: Incidence and severity of adverse events
研究概览
简要总结
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colorectal cancer.
详细描述
Main purpose:
To evaluate the safety of Claudin18.2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced colorectal cancer during the dose-escalation phase.
To determine the maximum tolerated dose of Claudin18.2-targeted CAR-DCs when administered in combination with CAR-T cells.
Secondary purpose:
To assess the overall response rate (ORR), including complete response (CR) and partial response (PR), as well as overall survival (OS) and disease-free survival (DFS) in patients receiving the combination therapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a histologically or cytologically confirmed diagnosis of colonic or rectal adenocarcinoma, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
- •Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
- •Disease progression following standard treatments, including prior administration of fluoropyrimidines, irinotecan, and oxaliplatin. Disease progression may occur during or after treatment. Prior molecular targeted therapies are allowed.
- •ECOG performance status of 0 to
- •Expected survival of at least 6 months.
- •Toxicities related to prior antitumor treatments must have resolved to baseline or ≤ Grade 1 (except for residual alopecia); peripheral neurotoxicity ≤ Grade 2 is acceptable. The minimum washout period is 4 weeks for chemotherapy and immunotherapy, and 2 weeks for targeted therapy.
- •Adequate organ function, defined as follows:
- •Hematologic function: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 75 × 10^9/L, and hemoglobin ≥ 9 g/dL. No blood transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), or erythropoietin (EPO) allowed within 14 days prior to hematology testing.
- •Hepatic function: Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN); AST and ALT < 2.5 × ULN. For patients with Gilbert's syndrome, TBIL < 2 × ULN. For patients with liver metastases, AST and ALT must be < 5 × ULN.
- •Renal function: Serum creatinine ≤ 1.5 × ULN; or if > 1.5 × ULN, creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockcroft-Gault formula.
- •Coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) < 1.5 × ULN; international normalized ratio (INR) < 1.5 or within the therapeutic range if on anticoagulation therapy.
- •Participants of childbearing potential must agree to use effective contraception during the study period.
- •Participants must have adequate comprehension and voluntarily sign the informed consent form.
- •Willingness to comply with all study-related procedures, including scheduled visits, drug administration, laboratory assessments, and other protocol requirements.
排除标准
- •Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
- •Clinically significant cardiovascular disease, including:
- •Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmias, or history of angioplasty, stent implantation, or coronary artery bypass grafting (CABG);
- •Prolonged QT/QTcF interval with clinical significance (QT/QTcF > 470 ms in females or > 450 ms in males).
- •Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
- •Active infections including HIV, syphilis, or active hepatitis B or C:
- •Hepatitis B: HBV-DNA ≥ 1000 IU/mL;
- •Hepatitis C: Positive HCV RNA with abnormal liver function.
- •History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
- •Presence of autoimmune diseases or chronic use of immunosuppressive agents or corticosteroids.
- •Poor medication compliance or inability to adhere to the treatment protocol.
- •Any other condition that, in the opinion of the investigator, warrants exclusion from the study.
研究组 & 干预措施
CAR-T and CAR-DC Combination Therapy
This arm involves the sequential administration of two biological interventions, with Claudin18.2-targeted CAR-DCs administered first, followed by Claudin18.2-targeted CAR-T cells.
干预措施: Claudin18.2-targeted CAR-T Cells (Biological)
CAR-T and CAR-DC Combination Therapy
This arm involves the sequential administration of two biological interventions, with Claudin18.2-targeted CAR-DCs administered first, followed by Claudin18.2-targeted CAR-T cells.
干预措施: Claudin18.2-targeted CAR-DCs (Biological)
结局指标
主要结局
Safety: Incidence and severity of adverse events
时间窗: First 3 month post CAR-T cells and CAR-DCs infusion
To evaluate adverse events occurring within the first three months following infusion of Claudin18.2-targeted CAR-T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Efficacy: Remission Rate
时间窗: 3 months post CAR-T cells and CAR-DCs infusion
To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)
次要结局
- Progression-Free Survival(Up to 24 months post CAR-T cells and CAR-DCs infusion)
- Overall Survival(Up to 24 months post CAR-T cells and CAR-DCs infusion)
- Relapse Rate(Up to 24 months post CAR-T cells and CAR-DCs infusion)
- Duration of Response(Up to 24 months post CAR-T cells and CAR-DCs infusion)
- In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring(First 2 weeks post CAR-T cells and CAR-DCs infusion)
- Objective Response Rate in Participants Receiving Different Doses of CAR-DCs(Up to 24 months post CAR-T cells and CAR-DCs infusion)
- Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs(Up to 24 months post CAR-T cells and CAR-DCs infusion)