Single-Arm Trial of EBV-Specific TCR-T Cells With Anti-PD1 Auto-secreted Element in the Treatment of EBV-Positive Head and Neck Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- The Maximum Tolerated Dose
研究概览
简要总结
Epstein-Barr virus (EBV) infections is known to be a high-risk factor to induce nasopharyngeal cancers. To date, EBV-related head and neck squamous cell carcinoma (HNSCC) is still a major concern in east Asia, especially in China. Concurrent therapies for HNSCC have limited response rate and high chance of relapse. However, EBV-induced cancers provided an ideal target for T cell-based immunotherapy due to the non-self origins. Engineered T cells bearing a TCR (TCR-T) that can specifically recognize the presented EBV antigen become a viable approach to treat this type of cancer. Though engineered T therapies have been well-recognized in hematological cancers, solid cancer treatment has been a major hurdle due to the immune-suppressive tumor microenvironment. One key mechanism of tumor-elicited suppression is the PDL1-PD1 interaction which induces T cell exhaustion. Therefore, TCR-T cells armed with a PD1 antagonist could further enhance the efficacy of TCR-T in solid cancers.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Expected to live longer than 12 weeks
- •Pathology confirmed as EBV positive HNSCC, either metastatic or recurrent disease
- •Creatinine <2.5mg/dl
- •ALT/AST is lower than three times ULN.
- •No contraindications of leukocyte collection
- •Before entering the trial, women must adopt a reliable method of contraception until 30 days after infusion.
- •Understand this trial and have signed an informed consent
排除标准
- •Patients with symptomatic brain metastasis
- •With other uncontrolled malignant tumors.
- •Hepatitis B or Hepatitis C activity period, HIV infected patients
- •Any other uncontrolled disease that interferes with the trial
- •Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis and cerebral hemorrhage
- •Untreated hypertension or hypertensive patients
- •A person with a history of mental illness that is difficult to control
- •Researchers do not consider it appropriate to participate in this trial
- •Patients who have been using immunosuppressive agents for a long time after organ transplants, except for recent or current inhaled corticosteroids
- •Subjects who have been pregnant or nursing, or who plan for pregnancy within 2 months of treatment or after the end of treatment
- •An illness affects a person who signs a written consent or complies with a study procedure, or who is unwilling or unable to comply with the research requirements
研究组 & 干预措施
EBV TCR-T
EBV-specific TCR-T cell with anti-PD1 auto-secreted element
干预措施: EBV-specific TCR-T cell with anti-PD1 auto-secreted element (Drug)
结局指标
主要结局
The Maximum Tolerated Dose
时间窗: 8 weeks
Verify the MTD of TCR-T cells for EBV antigen for treatment. 18 patients will be enrolled in this project, using a dose-escalation approach. The first group of patients will receive 5x10e6/kg TCR-T cells, the second group will receive 1x10e7/kg TCR-T cells, the third group will receive 5x10e7/kg TCR-T cells, the forth group will receive 1x10e8/kg. After confirmation of safety for 5×10e7 dose group, we then added IL-2 on this dose level for consecutive 6 patients. The remaining 6 pts are for enrollment of 1×10e8/kg dose level.
次要结局
未报告次要终点
研究者
Qingzhu Jia, M.D.
Doctor
Xinqiao Hospital of Chongqing