Efficacy and Safety of MSLN CAR-T in Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- TRAEs
研究概览
简要总结
- Study Title:
Efficacy and safety of MSLN CAR-T in advanced malignant tumors 2. Study Objectives:
Primary: To evaluate the safety and tolerability of MSLN-targeted CAR-T cell therapy in patients with stage III/IV advanced malignant tumors.
Secondary: To preliminarily evaluate the efficacy of MSLN-targeted CAR-T cell therapy in this patient population.
Exploratory: To assess in vivo expansion and persistence of infused MSLN-targeted CAR-T cells and explore correlations with clinical outcomes. 3. Participant Intervention:
Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and
-3 relative to the planned MSLN CAR-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.
详细描述
Detailed Description:
This is a prospective, interventional Phase I/II clinical study designed to evaluate the safety and efficacy of MSLN-targeted CAR-T cell therapy in patients with advanced malignant tumors. A total of 20 patients aged 18-75 years with unresectable, locally advanced, recurrent, or metastatic solid malignancies will be enrolled. All patients must have histopathologically confirmed disease and positive MSLN expression in tumor tissue.
MSLN CAR-T cells will be administered as a single intravenous infusion at a total dose of 0.5-2 × 10^6 CAR-T cells/kg. Eligible subjects (N=20) will be assigned by the investigator to receive MSLN CAR-T cell infusion.
Endpoints:
- Primary Endpoint:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 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
- •Aged 18-75 years (≥18 and ≤75 years), either sex;
- •The subject voluntarily participates in the study and provides written informed consent signed by the subject or his/her legally authorized representative;
- •Histopathologically confirmed unresectable, locally advanced, recurrent, or metastatic solid malignant tumor; according to the AJCC TNM staging system (8th edition, 2017), subjects diagnosed with stage III or stage IV solid malignant tumors;
- •Presence of measurable and evaluable lesions according to RECIST v1.1;
- •Positive MSLN expression in tumor tissue confirmed by immunohistochemistry (IHC);
- •The subject must have received standard first-line therapy and has experienced disease progression or is intolerant to such therapy;
- •The subject is not suitable for curative treatment modalities such as definitive chemoradiotherapy and/or surgery/immune checkpoint inhibitors, or refuses surgical resection;
- •No antibody-based therapy administered within 2 weeks prior to cell therapy;
- •ECOG performance status 0-2;
- •No contraindications to peripheral blood leukapheresis;
- •Estimated life expectancy ≥ 3 months.
排除标准
- •History of allergy to any component of the cell product;
- •Any of the following hematologic abnormalities on complete blood count (CBC): WBC ≤ 1 × 10^9/L, absolute neutrophil count (ANC) ≤ 0.5 × 10^9/L, absolute lymphocyte count (ALC) ≤ 0.5 × 10^9/L, or platelets (PLT) ≤ 25 × 10^9/L;
- •Any of the following laboratory abnormalities, including but not limited to: serum total bilirubin ≥ 1.5 mg/dL; serum ALT or AST > 2.5 × ULN; serum creatinine ≥ 2.0 mg/dL;
- •NYHA class III or IV heart failure per the New York Heart Association functional classification, or left ventricular ejection fraction (LVEF) < 50% on echocardiography;
- •Abnormal pulmonary function with oxygen saturation (SpO₂) < 92% on room air;
- •History of myocardial infarction, coronary angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
- •Grade 3 hypertension with poor blood pressure control despite medical treatment;
- •History of traumatic brain injury, disturbance of consciousness, epilepsy, or severe cerebral ischemic or hemorrhagic disease;
- •Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy;
- •Presence of uncontrolled active infection;
- •Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
- •Receipt of a live vaccine within 4 weeks prior to enrollment;
- •Positive test results for HIV, HBV, HCV, and TPPA/RPR, and/or HBV carriers;
- •History of alcohol abuse, illicit drug use, or psychiatric disorders;
- •Participation in any other clinical study within 3 months prior to enrollment;
- •Female subjects meeting any of the following:
- •pregnant or breastfeeding; or
- •planning pregnancy during the study period; or
- •of childbearing potential and unable/unwilling to use effective contraception;
- •Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.
研究组 & 干预措施
CART group
Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and
-3 relative to the planned MSLN CAR-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.
干预措施: CAR-T (Combination Product)
结局指标
主要结局
TRAEs
时间窗: From date of initial treatment to the 30 days after treatment
Adverse events during treatment
次要结局
- Disease-related clinical responses(From date of enrollment until the date of clinical responses,up to 2 years)