An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140203 T Cells and Determine the Recommended Phase II Dose (RP2D) in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-1)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT
研究概览
简要总结
Open-label, dose escalation, multi-center, Phase I / II study to assess the safety of an autologous T-cell product (ET140203) in adult subjects with Alpha-fetoprotein (AFP)-positive/Human Leukocyte Antigen (HLA) A-2-positive advanced hepatocellular carcinoma (HCC).
详细描述
The purpose of this study is to investigate an autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140203 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.
The trial was intended to be a Phase 1/2 trial, but the sponsor terminated the trial prior to moving to Phase 2 to direct their efforts to the pediatric study (ARYA-2) for this product.
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
- •Histologically confirmed HCC with serum AFP >100ng/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 two (2) different anti-HCC systemic agents
- •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 A6 or better
- •Absolute neutrophil count greater than or equal to 1,500/mm^3
- •Platelet count greater than or equal to 75,000/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 with the exception of cholangiocarcinoma (CCA) or any malignancy with an expected survival ≥ 3 years without any treatment (exception: hormone/androgen-deprivation 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 50% of the liver
研究组 & 干预措施
ET140203 TCells
ET140203 T Cells
干预措施: ET140203 autologous T cell product (Biological)
结局指标
主要结局
The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT
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 ET140203 T cells
时间窗: 28 days
Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion
Severity rates of adverse events (AEs) after infusion of ET140203 T cells
时间窗: 28 days
Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.
Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells
时间窗: 28 days
Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
次要结局
- Assess the efficacy of ET140203 T cells in adults with advanced HCC.(up to 2 years)
- Determine the pharmacokinetics of ET140203 T cells after infusion.(up to 2 years)