A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Dose-limiting toxicity (DLT) rate
研究概览
简要总结
A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma
详细描述
This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of CART cell in patients ≥ 18 years of age with relapsed or refractory advanced hepatocellular carcinoma. Patients who meet the eligibility criteria will receive cell infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up
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
- •Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent;
- •Age 18-75 years;
- •Patients diagnosed as advanced hepatocellular carcinoma (HCC) histopathologically or cytologically; Progression or intolerance after previous standard systemic therapy;
- •GPC3 is detected positive by immunohistochemistry (IHC);
- •Child-Pugh score ≤ 7;
- •At least one assessable tumor lesion;
- •ECOG score: 0-1;
- •Expected survival ≥ 3 months;
- •Clinical laboratory values meet screening visit criteria
排除标准
- •Previous CAR-T cell, TCR-T cell or other cell therapies or therapeutic tumor vaccination directed at any target;
- •Any previous GPC3 targeted therapy;
- •Prior antitumor therapy with insufficient washout period;
- •Brain metastases with central nervous system symptoms;
- •Pregnant or lactating women
- •HCV-Ab or/and HIV-Ab positive; active syphilis;
- •Severe underlying diseases
- •Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.
结局指标
主要结局
Dose-limiting toxicity (DLT) rate
时间窗: Minimum 2 years after CART infusion (Day 1)
Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.
Recommended Phase 2 dose (RP2D) finding
时间窗: 30 days after CART infusion (Day 1)
RP2D established through ATD+BOIN design
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: Minimum 2 years after CART infusion (Day 1)
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment
CAR positive T cells
时间窗: Minimum 2 years after CART infusion (Day 1)
CAR positive T cells after CART infusion
CAR transgene levels in peripheral blood
时间窗: Minimum 2 years after CART infusion (Day 1)
CAR transgene levels in peripheral blood after CART infusion
次要结局
- Disease control rate (DCR)(Minimum 2 years after CART infusion (Day 1))
- Overall Survival (OS)(Minimum 2 years after CART infusion (Day 1))
- Incidence of anti-CART antibody(Minimum 2 years after CART infusion (Day 1))
- Progress Free Survival (PFS)(2 years after CART infusion (Day 1))
- Duration of Response(DoR)(Minimum 2 years after CART infusion (Day 1))
- Time to Response (TTR)(Minimum 2 years after CART infusion (Day 1))
- Overall response rate (ORR)(Minimum 2 years after CART infusion (Day 1))
研究者
jianming xu
Leading Site Principal Investigator
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences