NCT04684459招募中早期 1 期
Phase I Study of Specific CAR-T Dual-targeting HER2 and PD-L1 for HER2-positive Solid Tumors
Sichuan University1 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2021年3月12日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
CAR-T therapy has achieved unprecedented success in hematological tumors in recent years, but the progress of CAR-T cells in the treatment of solid tumors is facing difficulties. HER-2 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors. In this study, the PD-L1 inhibitory signal was transformed into an activation signal in the tumor microenvironment, and enhanced the killing activity and survival ability of CAR-T cells. The HER-2/PD-L1 dual-targeting CAR-T will be investigated in patients with HER2-positive solid tumors, and all enrolled subjects will receive HER2/PD-L1 CAR T cells via intravenous or thoracic/peritoneal cavity infusion.
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
- •Male or female, Age 18-75 years old; If the subjects are over 75 years old, the researchers will determine whether to enroll according to the basic health conditions of the subjects, regardless of gender. No upper age limit was set for chest/abdominal reinfusion CAR-T subjects.
- •Estimated life expectancy ≥ 3 months (according to investigator's judgement);
- •The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;
- •Patients diagnosed as ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, pancreatic cancer, colorectal cancer, transitional cell carcinoma, endometrial carcinoma, sarcoma, glioblastoma, cholangiocarcinoma, etc. have received standard systemic treatment, have systemic metastasis/serosal cavity metastasis or are not tolerated;
- •Expressing HER2 >20% of primary tumors or metastatic cells in the serous cavity by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH);
- •Absolute neutrophil count ≥ 1×10^9/L, platelet count ≥ 75×10^9/L, absolute lymphocyte count ≥0.5×10^8/L, hemoglobin ≥ 8.0 g/dl;
- •Creatinine clearance rate ≥60ml/min, Serum ALT/AST≤2.5 times of the normal level, and total bilirubin≤1.5 times of the normal level;
- •Cardiac ejection fraction ≥50%, no pericardial effusion;
- •No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy);
- •Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment;
- •Patients must take reliable contraceptive measures before entering the trial, during the research process until 1 year after CAR-T infusion; reliable contraceptive measures will be determined by the main investigator or designated personnel;
- •Voluntarily participate in the research, understand and sign the informed consent;
- •The side effect of the last anti-tumor treatment was reduced to ≤1 grade, except for hair loss.
排除标准
- •Allergic to cytokines;
- •Uncontrolled activity infection;
- •Acute or chronic (graft-versus-host disease) GVHD;
- •Accompanied by other uncontrolled malignant tumors;
- •Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;
- •Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;
- •Patients with grade 2-3 hypertension or poorly controlled;
- •History of mental illness that is difficult to control;
- •Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy;
- •The existing medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or the administration of the study drug;
- •Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy;
- •Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends;
- •Patient suffering from diseases that have signed written informed consent or comply with research procedures; or are unwilling or unable to comply with research requirements.
研究组 & 干预措施
CAR-T cell therapy
Experimental
Dual-targeting HER2 and PD-L1 CAR-T cell therapy
干预措施: Dual-targeting HER2 and PD-L1 CAR-T cells (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: 12 months
Baseline up to 28 days after CAR-T cells infusion
Incidence of Treatment-Related Adverse Events
时间窗: 12 months
AE during the first 28 days after CAR-T cell administration
次要结局
- ORR（objective response rate）(Month 1，month 3, month 6)
- DOR (duration of response)(12 months)
研究者
Yongsheng Wang
Director of Institute of Drug Clinical Trial of West China Hospital
Sichuan University
研究点 (1)
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