Clinical Study of Combined EphA2-targeted CAR-DC and CAR-T Cell Therapy for Non-small Cell Lung 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 EphA2-targeted CAR-DC combined with CAR-T cell therapy in patients with non-small cell lung cancer.
详细描述
Main purpose:
To evaluate the safety of EphA2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced non-small cell lung cancer during the dose-escalation phase.
To determine the maximum tolerated dose of EphA2-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
- •Pathologically confirmed stage IV non-small cell lung cancer (NSCLC) with at least one measurable lesion according to RECIST 1.1 criteria (i.e., a lesion with the longest diameter ≥10 mm on spiral CT scan or a lymph node with a short axis ≥15 mm).
- •Tumor tissue tested positive for EphA2 expression by immunohistochemistry (≥20%).
- •Disease progression after standard treatment or no available standard treatment (patients must have received at least two prior systemic therapies, including but not limited to chemotherapy and immune checkpoint inhibitors; patients with actionable driver mutations must have failed targeted therapy).
- •ECOG performance status: 0-
- •Expected survival ≥6 months.
- •Toxicities related to prior anti-tumor treatments must have resolved to baseline levels or ≤ Grade 1 (excluding residual alopecia); Grade ≤2 neurotoxicity is acceptable. Washout periods: 4 weeks for chemotherapy and immunotherapy, 2 weeks for targeted therapy.
- •Adequate organ function, including:
- •Adequate hematologic function: Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥75×10^9/L, hemoglobin ≥9 g/dL. No transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin allowed within 14 days before blood tests.
- •Adequate 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; if liver metastases are present, AST and ALT <5×ULN.
- •Adequate renal function: Serum creatinine (Cr) ≤1.5×ULN, or if Cr >1.5×ULN, creatinine clearance (CrCl) ≥60 mL/min calculated using the Cockcroft-Gault formula.
- •Adequate coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) <1.5×ULN; international normalized ratio (INR) <1.5 or within the target range if on anticoagulant therapy.
- •Subjects of reproductive potential must be willing to use effective contraception.
- •Ability to understand and voluntarily sign the informed consent form.
- •Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
排除标准
- •Pathologically confirmed mixed histology, such as adenosquamous carcinoma of the lung.
- •Tumor-related emergencies requiring urgent treatment, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
- •Significant cardiovascular diseases, including:
- •Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmia, or having undergone angioplasty, stent implantation, or coronary artery bypass surgery.
- •Clinically significant QT/QTcF prolongation (QT/QTcF > 470 ms in females or > 450 ms in males).
- •Clinically significant bleeding tendency or coagulation disorders, such as hemophilia.
- •HIV or syphilis infection; active hepatitis B or C:
- •Hepatitis B: HBV-DNA ≥ 1000 IU/mL.
- •Hepatitis C: Positive HCV RNA with abnormal liver function.
- •History of involuntary commitment due to psychiatric disorders or other psychological conditions deemed unsuitable for treatment by the investigator.
- •Presence of other autoimmune diseases, or long-term use of immunosuppressive agents or corticosteroids.
- •Poor medication compliance.
- •Any other condition that the investigator considers grounds for exclusion.
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 EphA2-targeted CAR-DCs administered first, followed by EphA2-targeted CAR-T cells.
干预措施: EphA2-targeted CAR-T Cells (Biological)
CAR-T and CAR-DC Combination Therapy
This arm involves the sequential administration of two biological interventions with EphA2-targeted CAR-DCs administered first, followed by EphA2-targeted CAR-T cells.
干预措施: EphA2-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 EphA2-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)