JWATM214，an Armored GPC3-directed CAR-T ，in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma ：a Single-arm, Open-label，Dose-escalation Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Treatment-related adverse events (AEs)
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 armored 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 guideline or consensus for hepatocellular carcinoma are expected at screening, judged by investigators
- •Fresh samples or FFPE, immunohistochemistry (IHC)-stained GPC-3 positive with intensity ++ or +++
- •Per RECIST v1.1, at least one measurable lesion
- •Manageable lung metastasis
- •Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
- •No active HBV infections
- •Adequate organ functions
- •Adequate venous access for APH
- •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-hCG test result at screening and 48 hours prior to lymphodepletion
排除标准
- •Cholangiocarcinoma or histological-mixed hepatocellular cholangiocarcinoma
- •Active brain metastasis
- •Primary lesion or infused lesions with the longest diameter ≥15cm, 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 (TCR-T/CAR-T) or other CGT
- •Active HCV, HIV, or syphilis
- •History of organ transplant
- •Uncontrolled or active infection at screening, prior to APH, 72 hours prior to lymphodepletion or 5 days prior to JWATM214 infusion
- •With severe cardiovascular disease
- •History or presence of clinically-relevant CNS disorders
- •Current presence of hepatic encephalopathy
- •≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants
- •Active digestive ulcer or gastrointestinal bleeding within 3 months prior to screening
- •Pregnant or lactating women
- •Not satisfying wash-out period for APH
- •Unable or unwilling to comply with the study protocol, judged by the investigator
- •Other situations implying that the subject might not be appropriate to participate in the study
- •Previously allergic or intolerable to JWATM214 or its components
研究组 & 干预措施
CAR-GPC3 T cells
The safety and efficacy of JWATM214 will be evaluated in a 'BOIN'-designed dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10^8, 3×10^8, and 10×10^8, whereas the dosage 0.5×10^8 and 30×10^8 CAR-T cells will be selected as optional back-up doses for potential escalation or de-escalation.
干预措施: CAR-GPC3 T cells (Biological)
结局指标
主要结局
Treatment-related adverse events (AEs)
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.
Dose-limiting toxicities
时间窗: 28 days
DLT (Dose-limiting toxicity) was an adverse event that occurred within 28 days after JWATM214 infusion that met any of the following criteria. 1. Any grade ≥3 nonhematologic toxicity associated with JWATM214 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators 2. Hematologic toxicity 3. Grade ≥3 anaphylaxis 4. Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment. 5. ≥ grade 3 autoimmune toxicity during treatment 6. Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours. 7. 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. 8. Grade 5 events of any nonmalignant cause.
RP2D of JWATM214 in HCC patients
时间窗: 2 years
Recommended phase 2 dose of JWATM214
次要结局
- progression-free survival (PFS)(2 years)
- Objective response rate (ORR).(1 years)
- Disease Control Rate(2 years)
- overall survival (OS)(2 years)
- PK of JWATM214 in the peripheral blood (qPCR)(1 years)