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临床试验/NCT03349255
NCT03349255终止1 期

Phase 1, Open-label, Two Routes IV and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-CAR T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

Aeon Therapeutics (Shanghai) Co., Ltd.1 个研究点 分布在 1 个国家目标入组 3 人开始时间: 2017年10月6日最近更新:
适应症
干预措施

试验速览

阶段
1 期
状态
终止
发起方
入组人数
3
试验地点
1
主要终点
Toxicity profile of ET1402L1-CART-cell treatment

研究概览

简要总结

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC

详细描述

The molecular target for ET1402L1-CART is alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ET1402L1-CART is a second generation (CD28/CD3ζ) chimeric antigen receptor (CAR) engineered with a human single-chain variable antibody fragments (scFv) against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-CART-cells in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Patients with lesion(s) localized in liver will be enrolled in the IA arm, with the ET1402L1-CART-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the IV arm, with the ET1402L1-CART-cells administered through intravenous infusion.

研究设计

研究类型
Interventional
分配方式
Non Randomized
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

入选标准

  • AFP-expressing HCC and serum AFP >100 ng/mL.
  • Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 20 mm.
  • Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
  • Child-Pugh score of A or B
  • Life expectancy > 4 months
  • Age at time of enrollment is ≥18 years of age.
  • Adequate organ function as defined below:
  • A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute.
  • Patients must have a serum direct bilirubin ≤2 x ULN, ALT and AST ≤5 times the institutional upper limits of normal.
  • Ejection Fraction measured by echocardiogram or MUGA >45% (evaluation done within 6 weeks of screening does not need to be repeated)
  • DLCO or FEV1 >45% predicted
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
  • Platelet count ≥ 50,000/mm3 (10^9/L)
  • Negative serum pregnancy test for women with childbearing potential
  • Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

排除标准

  • Patients with decompensated cirrhosis: Child-Pugh Score C
  • Patients with an organ transplantation history
  • Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
  • Patients with dependence on corticosteroids
  • Patients with active autoimmune diseases requiring systemic immunosuppressive therapy
  • Patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery
  • Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
  • Patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.).
  • Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. Patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled.
  • Patients with other uncontrolled diseases, such as active infections:
  • Acute or chronic active hepatitis B or hepatitis C.
  • HIV-infection
  • Women who are pregnant

研究组 & 干预措施

intravenous (i.v.) arm

Experimental

autologous ET1402L1-CART cells administered by intravenous (IV) infusion

干预措施: autologous ET1402L1-CART cells (Biological)

intra-hepatic artery (i.a.) arm

Experimental

autologous ET1402L1-CART cells administered by intra-hepatic artery (IA) infusion

干预措施: autologous ET1402L1-CART cells (Biological)

结局指标

主要结局

Toxicity profile of ET1402L1-CART-cell treatment

时间窗: 28 days up to 2 years

Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET1402L1-CART T cells related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits.

Number of patients with dose-limiting toxicity

时间窗: 28 days up to 2 years

A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET1402L1-CART-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.

次要结局

  • AFP expression in tumors(4-8 weeks)
  • Time to baseline for serum cytokine levels(24 weeks)
  • Rate of disease response by RECIST in the liver(2 years)
  • AFP serum levels(2 years)
  • Anti-tumor responses(4 months, 1 year, 2 years)
  • CART cell engraftment(2 years)
  • Rate of disease response by RECIST at non-liver sites(2 years)
  • Tmax of serum cytokine levels(24 weeks)
  • AUC of serum cytokine levels(24 weeks)

研究者

发起方
Aeon Therapeutics (Shanghai) Co., Ltd.
申办方类型
Industry
责任方
Sponsor

研究点 (1)

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