An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140202 T Cells and Determine the Recommended Phase II Dose ("RP2D") in Adults With Advanced Hepatocellular Carcinoma ("HCC")
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 6
- 主要终点
- The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
研究概览
简要总结
This is a open-label, dose escalation, multi-center, Phase I / Phase II study to assess the safety of an autologous T-cell product (ET140202) in adult subjects with advanced Alpha-fetoprotein (AFP) positive/Human Leukocyte Antigen (HLA) A-2 positive Hepatocellular Carcinoma (HCC).
详细描述
The purpose of this study is to investigate a genetically modified autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140202 T cells are autologous T cells genetically modified to carry a TCR-mimic (TCRm) construct capable of mediating cell killing by targeting tumor specific intracellular antigens and addressing solid tumor therapy challenges.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent obtained prior to study procedures
- •Histologically confirmed HCC with serum AFP >200ng/ml at time of screening and following most current line of therapy OR radiographic diagnosis of HCC with serum AFP >400ng/ml at time of screening and following most current line of therapy..
- •Metastatic or locally advanced, unresectable HCC
- •Must have failed or not tolerated, at least one line of systemic therapy for advanced HCC
- •Molecular Human Leukocyte Antigen ("HLA") class I allele typing confirms participant carries at least one HLA-A2 allele
- •Life expectancy of at least 4 months
- •Karnofsky Performance Scale greater than or equal to 70
- •At least 1 measurable lesion on imaging by RECIST
- •Child-Pugh A or B7
- •Absolute neutrophil count greater than or equal to 1,500/mm^3
- •Platelet count greater than or equal to 30,000/mm^3
排除标准
- •Clinically significant cardiac disease
- •Clinically significant pre-existing illness or active infection
- •Clinically significant Central Nervous System (CNS) or neural dysfunction
- •Active autoimmune disease requiring therapy
- •Active malignancy other than HCC unless expected survival is greater than or equal to three years without any treatment (exception: hormone/androgen-depravation therapy) and without any organ involvement
- •History of organ transplant
- •Compromised circulation in portal vein, hepatic vein, or vena cava due to obstruction
- •Advanced HCC involving greater than one-third of the liver
结局指标
主要结局
The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
时间窗: up to 2 years
The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response
Incidence rates of adverse events (AEs) after infusion of ET140202 T cells
时间窗: 28 days
Safety and tolerability of ET140202 T cells as assessed by committee review of dose limiting toxicities (DLTs) and incidence and severity of adverse events (AEs) after infusion
次要结局
- Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess the persistence of ET140202 T cells circulating in blood over time.(up to 2 years)
- Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess the expansion of ET140202 T cells in the blood shortly after infusion.(up to 2 years)