A Clinical Study on the Safety and Efficacy of GCC Targeting CAR-T Cells (WD-01) for Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is an investigator initiated trial to assess the efficacy and safety of a GCC-targeting CAR-T therapy (WD-01) in the metastatic colorectal cancer.
详细描述
The study will use autologous T cells collected from enrolled patient, modified using a 2nd generation CAR bearing lentiviral vector, to treat metastatic colorectal cancer patients. The antigen-binding site of the CAR molecule recognizes GCC as the target.
The main questions it aims to answer are: • What is the maximum tolerated dose (MTD) of GCC-CAR-T therapy in the autologous CAR-T cell treatments? • What are the dose-limiting toxicities (DLT) and treatment-emergent adverse events (TEAE)? • What is the treatment efficacy, as measured by objective response rate (ORR) and progression-free survival (PFS)? Investigators will assess whether the WD-01 CAR-T cells have good safety and efficacy in treating colorectal cancer. Participants will receive WD-01 GCC-CAR-T cells through a 3+3 dose escalation scheme. • Undergo chemotherapy pre-conditioning before CAR-T infusion. • Be monitored for adverse events, immune response, and disease progression.
The study will collect data on both short-term outcomes (within the first few months post-treatment) and long-term safety and efficacy.
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
- •Pathologically confirmed colorectal cancer. Immunohistochemistry (IHC) assessment shows GCC expression in tumor lesions of ≥1+ in an average of over 40% of the area (evaluated by randomly selecting at least five tumor regions).
- •Patients with metastatic colorectal cancer who have failed second-line treatment.
- •At least one measurable extracranial lesion per RECIST version 1.1 criteria. Expected survival of ≥90 days.
- •Normal function of major organs, meeting the following criteria:
- •ECOG performance status of 0-1 or KPS score >
- •Hematology parameters meeting: Hemoglobin (HB) ≥80 g/L, Absolute Neutrophil Count (ANC) ≥1.5 × 10^9/L, Platelets (PLT) ≥80 × 10^9/L, Lymphocytes (LY) ≥0.5 × 10^9/L.
- •Biochemistry parameters meeting: Total Bilirubin (TBIL) ≤2.0 × ULN (upper limit of normal); ALT and AST ≤2.5 × ULN; Serum Creatinine (Cr) ≤1 × ULN, Creatinine Clearance Rate >40 mL/min (by Cockcroft-Gault formula).
- •Left ventricular ejection fraction >55%. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use appropriate contraception during the study and for 8 weeks after the last CAR-T administration (women who have undergone sterilization or have been postmenopausal for at least 2 years are considered not of childbearing potential).
- •Voluntary participation in the study, with signed informed consent, good compliance, and willingness to cooperate with follow-up.
排除标准
- •Pregnant or lactating women. Receipt of small molecule chemotherapy, targeted agents, other investigational drugs, or monoclonal antibodies within 14 days prior to cell collection for enrollment.
- •Participation in other clinical trials within 4 weeks prior to the start of this study.
- •Uncontrolled hypertension that cannot be adequately managed with a single antihypertensive drug (systolic BP >160 mmHg, diastolic BP >100 mmHg), myocardial ischemia or infarction of grade ≥1, arrhythmia of grade ≥1 (including QT interval ≥440 ms), or cardiac insufficiency.
- •Long-standing, unhealed wounds or fractures. History of substance abuse that cannot be discontinued or a history of psychiatric disorders.
- •Severe intestinal adhesions, bowel obstruction, or conditions that may cause bowel perforation or abdominal wall fistula after treatment.
- •Uncontrolled or active fungal, bacterial, viral, or other infections. Grade ≥2 hematologic toxicity or grade ≥3 non-hematologic toxicity at enrollment as per NCI-CTCAE version 5.0 criteria.
- •Known HIV infection or active hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) infection.
- •Presence of indwelling catheters or drainage tubes (e.g., biliary drainage tubes or thoracic/abdominal drainage tubes or pericardial catheters). Use of specialized central venous catheters is permitted.
- •Severe malnutrition (for patients <70 years, BMI <18.5 kg/m^2; for patients ≥70 years, BMI <20 kg/m^2).
- •History of severe allergic reactions to key therapeutic agents in this study (including fludarabine, cyclophosphamide, mesna, tocilizumab, and anti-infective drugs used during preconditioning).
- •History of disseminated intravascular coagulation (DIC), deep vein thrombosis, or pulmonary embolism within 6 months prior to enrollment.
- •History of autoimmune diseases that cause terminal organ damage or require systemic immunosuppressive/systemic disease-modifying drugs within 2 years prior to enrollment (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
- •Any disease that may interfere with the safety or efficacy assessment of the study treatment.
- •Female participants who are unwilling to use contraception from the time of consent until 6 months after completing CAR-T cell infusion.
研究组 & 干预措施
Single dose injection of WD-01
Dose escalation will be performed for the single dose injection of WD-01 for treating mCRC
干预措施: An armored GCC targeting WD-01 CAR-T to treat cancer patients Other Name: (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Within the first month post-infusion
The highest dose of GCC-CAR-T cells that can be administered without causing unacceptable side effects, measured during the dose escalation phase.
Dose-Limiting Toxicities (DLT)
时间窗: Within the first month post-infusion
The incidence of treatment-related toxicities that prevent further dose escalation.
Treatment-Emergent Adverse Events (TEAE)
时间窗: From the administration of WD-01 CAR-T cells through six months post-infusion
The frequency and severity of adverse events that arise following the administration of WD-01 CAR-T cells.
次要结局
- Overall Survival (OS)(From the start of treatment up to maximum follow-up period of five years)
- Duration of Response (DOR)(From the administration of WD-01 CAR-T cells to a maximum follow-up period of five years)
- Progression-Free Survival (PFS)(From the start of treatment up to 5 years)
- Objective Response Rate (ORR)(Measured between 1 and 6 months after treatment)