A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors
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 and severity of adverse events (AEs) and severe adverse events (SAEs)
研究概览
简要总结
A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.
详细描述
This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic 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 year-old, male or female
- •Voluntarily willing to participate in the study and sign the written informed consent form
- •Life expectation ≥12 weeks
- •European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
- •Histologically-confirmed recurrent/metastatic advanced solid tumors
- •Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators
- •Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive
- •Human leukocyte antigen (HLA)-A*02 allele matched
- •Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion
- •Adequate organ functions
- •Adequate venous access for APH
- •Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), 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 1 year post infusion, and sperm donation is prohibited during the study
- •Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion
排除标准
- •Pregnant or lactating women
- •Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
- •Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
- •Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- •Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
- •Systematic autoimmune disorders requiring long-term systematic treatment
- •Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT)
- •History of organ transplant
- •Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion
- •Subjects with other serious diseases that may restrict them from participating in this study
- •Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc
- •Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants
- •Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening
- •Not satisfying wash-out period for APH
- •Previously allergic or intolerable to JWTCR001 or its components
- •Unable or unwilling to comply with the study protocol, judged by the investigators
- •Other situations implying that the subject might not be appropriate to participate in the study
研究组 & 干预措施
TCR-MAGE-A4 T-Cells
The subjects enrolled will be sequentially assigned to the corresponding dose level.
干预措施: TCR-MAGE-A4 T-Cells (Drug)
结局指标
主要结局
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 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 JWTCR001 infusion that met any of the following criteria. Any Grade ≥3 non-hematologic toxicity associated with JWTCR001 that has not resolved to Grade ≤2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators. Grade ≥3 hematological toxicities. 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 TCR-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 clinically-significant abnormalities in laboratory testings
时间窗: 2 years
Clinically-significant abnormalities in laboratory testings.
次要结局
- Copy number of the vector transgene of JWTCR001 in peripheral blood(2 years)
- MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood(2 years)
- Antitumor efficacy-Progression-free survival (PFS)(2 years)
- Antitumor efficacy-Duration of response (DOR)(2 years)
- Antitumor efficacy-Time to response (TTR)(2 years)
- Antitumor efficacy-Overall survival (OS)(2 years)
- Antitumor efficacy-Objective response rate (ORR)(2 years)
- Antitumor efficacy-Disease control rate (DCR)(2 years)
研究者
Shen Lin
Professor
Peking University