A Phase 1, Single-arm, Open-label, Dose-escalation Study of JWATM204 as T Cell-targeted Immunotherapy in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Rate of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.
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
- •18-75 years-old, male or female
- •Voluntarily willing to participate in the study and sign the written informed consent form
- •Life expectation ≥12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
- •Histologically-confirmed hepatocellular carcinoma (HCC)
- •No benefits from curative surgery or other local therapies are expected at screening, judged by investigators
- •Radiologically-confirmed progression disease after at least one prior line of systematic treatment and limited benefits from current available options for hepatocellular carcinoma are expected at screening, judged by investigators
- •Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained GPC-3 positive
- •Per RECIST v1.1, at least one measurable lesion
- •Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
- •No active infections of hepatitis B virus
- •Adequate organ functions
- •Adequate venous access for apheresis
- •Non-hematological AEs induced by previous treatment must have recovered to CTCAE ≤1, except for alopecia and peripheral neuropathy
- •Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1year post infusion, and sperm donation is prohibited during the study
- •Women of childbearing potential must have negative serum β-human chorionic gonadotropin (β-hCG) test result at screening and 48 hours prior to lymphodepletion
排除标准
- •Active brain metastasis
- •Primary lesion or infused lesions with the longest diameter ≥15 cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator
- •Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- •Systematic autoimmune disorders requiring long-term systematic immunosuppression
- •Previously treated with any genetically engineered modified T-cell therapy nor other cell-gene therapy
- •Active infections of hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis
- •Uncontrolled or active infection at screening, prior to apheresis, 72 hours prior to lymphodepletion or 5 days prior to JWATM204 infusion
- •With severe cardiovascular disease History or presence of clinically-relevant central nervous system (CNS) disorders
- •With clinically-significant CNS disorders
- •Current presence of or previously with hepatic encephalopathy
- •≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants
- •Pregnant or lactating women
- •Not satisfying pre-defined wash-out period for apheresis
- •Received plasma exchange within 14 days prior to apheresis
- •Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study
- •Vaccinated with live vaccinations against infectious diseases within 8 weeks prior to JWATM204 infusion
- •Previously allergic or intolerable to JWATM204 or its components
结局指标
主要结局
Rate of dose-limiting toxicities (DLTs)
时间窗: 28 days
Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWATM204 infusion that met any of the following criteria. Any grade ≥3 nonhematologic toxicity associated with JWATM204 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators Hematologic toxicity Grade ≥3 anaphylaxis Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment. ≥ grade 3 autoimmune toxicity during treatment Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours. Grade ≥3 CAR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to grade ≤2 within 72 hours. Grade 5 events of any nonmalignant cause.
Rate and severity of adverse events (AEs) and severe adverse events (SAEs)
时间窗: 2 years
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Rate and severity of clinically-significant abnormalities in laboratory testings
时间窗: 2 years
Clinically-significant abnormalities in laboratory testings.
次要结局
- Disease Control Rate (DCR)(2 years)
- Copy number of the vector transgene of JWATM204 in peripheral blood(1 year)
- Objective response rate (ORR)(2 years)
- Progression-free survival (PFS)(2 years)
- Overal survival (OS)(2 years)