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
- 3
- 主要终点
- Incidence rates of adverse events (AEs) after infusion of ET140202 T cells
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
研究组 & 干预措施
ET140202 T cells
ET140202 Receptor (+) T Cells
干预措施: ET140202 autologous T cell product (Biological)
结局指标
主要结局
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
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
次要结局
- 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)
- 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 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 partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)