临床试验/NCT03874897

NCT03874897已完成1 期

An Open Label, Single/Multiple Dose Exploratory Clinical Study to Evaluate the Safety, Efficacy, and Cytokinetics of Autologous Humanized Anti-claudin18.2 Chimeric Antigen Receptor T Cell in Advanced Solid Tumor Subjects

Peking University3 个研究点分布在 1 个国家目标入组 134 人开始时间: 2019年3月26日最近更新: 2024年4月30日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 134
试验地点: 3
主要终点: Dose-limiting toxicity (DLT)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

An open label, single/multiple dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor.

详细描述

This study is an open, single/multiple infusion, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of CAR-CLDN18.2 T cell therapy, and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumor with positive claudin 18.2 expression and failed to standard systemic treatment.

研究设计

研究类型: Interventional
分配方式: Non Randomized
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

•Aged 18 to 75 years, male or female;
•Subjects with pathologically confirmed solid tumors (ie, advanced gastric cancer, esophagogastricgastroesophageal junction cancer, and pancreatic cancer) and have been failed to at least first-one prior line of systemic treatment;
•Tumor tissue samplessample was positive for claudin 18.2 positive through for claudin18.2 IHC staining;assay(≥2+, and ≥40%);
•Estimated life expectancy > 12 weeks;
•According to the RECIST 1.1, there is at least one measurable or unmeasurable tumor lesionslesion；
•ECOG physical status score 0 ~ 1, within 24 hours prior to apheresis, and at baseline (prior to pre-treatment);
•Sufficient venous access for mononuclear cell collection (abbreviation: apheresis)
•Subjects should have adequate organ functions before screening and pre-treatment (at baseline).
•Female subjects of childbearing age must undergo a serum pregnancy test at screening and prior to preconditioning and the results must be negative, and are willing to use a very effective and reliable method of contraception within 1 year after the last study treatment. The methods that can be used are: bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusion; or approved oral, injection or hormone-imparting contraceptive methods; or barrier contraceptive method: containing spermicidal foam / Gel/film/cream/suppository condom or occlusive cap (diaphragm or cervix/cap);
•Men who have actively sexual intercourse with women with child-bearing potential, must agree to use barrier-based contraception if they have no vasectomy, for example, a condom containing a spermicidal foam/gel/film/paste/suppository, or use a contraceptive method for their spouse (see article 9 of the inclusion criteria). Moreover, all men are absolutely forbidden to donate sperm within 1 year after receiving the last study treatment infusion；
•Subject participates in this clinical trial and sign Informed Consent Form voluntarily.

排除标准

•Pregnant or lactating women;
•HIV, Treponema pallidum or HCV serologically positive;
•Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection (HBsAg positive, or HBcAb positive and HBV DNA positive);
•Subjects have clinically significant thyroid dysfunction determined by investigator (serum thyroid hormone assays TT4, TT3, FT3, FT4, and serum thyroid stimulating hormone TSH) which is not suitable for entering into the study;
•The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and, hyperpigmentation or other tolerable events determined by investigator or laboratory abnormalities allowed by the protocol;
•Subjects who are using steroidshave recieved ≥15 mg/day glucocorticoid systemically currently within 7 days prior to apheresis; those using inhaled steroids recently or currently are not excluded;
•Previously allergic to immunotherapy and related drugs, history of severe allergiespreconditioning drug such as cyclophosphamide, fludarabine, or allergiestocilizumab or allergic to components of CT041CAR-CLDN18.2T injection, allergic to β-lactam antibiotics;the CT041 infusion;
•Previously received any chimeric antigen receptor-modified T-cells(including CAR-T、TCR-T) .
•Subjects have untreated or symptomatic brain metastases;
•Subjects have central or extensivelywith centralcor diffused metastases in lung and .extensiveor diffused metastases in liver;liveror with rapid tumor progression since screening period evaluated by the investigator preconditioning (at baseline)；
•The largest target tumor lesion>4cm
•Subjects with unstable or active ulcers and gastrointestinal bleeding currently;
•Subjects with a history of organ transplantation or awaiting organ transplantation;
•Subjects requiring anticoagulant therapy;
•Subjects requiring continuous anti-platelet therapy;
•Subjects who have undergone major surgery or significant trauma within 4 weeks prior to apheresis, or who are expected to undergo major surgery during the study;
•There are no other serious diseases that may limit subjects' participation in this trial;
•The investigator assessed that the subject was unable or unwilling to comply with the requirements of the study protocol;
•Blood oxygen saturation ≤ 95% before pre-treatmentapheresis or preconditioning (accept finger oxygen detection method);
•Prior to pretreatmentpreconditioning, subjects developed, including but not limited to, new arrhythmias that could not be controlled with drugs, hypotension requiring pressor agent, bacterial, fungal or viral infections that required intravenous antibiotics. Creatinine clearance rate <40mL / min; The investigator judges that the subject is not suitable for continuing the trial. Subjects who use antibiotics to prevent infection can continue the trials if judged by the investigator;
•The subject has a central nervous system disease sign or an abnormal neurological test result with clinical significance;
•The subject is currently suffered from or have suffered from other incurable malignant tumors within previous 3 years, except in situ cervical cancer or skin basal cell cancer.

研究组 & 干预措施

CAR-CLDN18.2 T-Cells

Experimental

The subjects enrolled will be sequentially assigned to the corresponding dose level.

干预措施: CAR-CLDN18.2 T-Cells (Drug)

Cohort 1

Experimental

CT041 monotherapy in patients with GI cancers who failed standard chemotherapy

干预措施: CAR-CLDN18.2 T-Cells (Drug)

Cohort 2

Experimental

CT041 plus anti-PD1 therapy in patients with GI cancers who failed standard chemotherapy

干预措施: CAR-CLDN18.2 T-Cells (Drug)

Cohort 2

Experimental

CT041 plus anti-PD1 therapy in patients with GI cancers who failed standard chemotherapy

干预措施: PD-1 Monoclonal Antibody (Drug)

Cohort 3

Experimental

CT041 sequential treatment after first-line therapy in GC/GEJ

干预措施: CAR-CLDN18.2 T-Cells (Drug)

Cohort 3

Experimental

CT041 sequential treatment after first-line therapy in GC/GEJ

干预措施: Chemotherapy (Drug)

Cohort 4

Experimental

prior treatment failure to anti-CLDN18.2 monoclonal antibody

干预措施: CAR-CLDN18.2 T-Cells (Drug)

结局指标

主要结局

Dose-limiting toxicity (DLT)

时间窗: 28 days of single infusion

Safety

Maximum tolerated dose (MTD)

时间窗: 28 days of single infusion

tolerability

次要结局

Antitumor efficacy-Progression-free survival (PFS)(1 year)
Antitumor efficacy-Duration of response (DOR)(1 year)
Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)(26 weeks)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(1 year)
Antitumor efficacy-Duration of disease control (DDC)(1 year)
Antitumor efficacy-Overall survival (OS)(1 years)
Antitumor efficacy-Objective response rate (ORR)(1 year)
Antitumor efficacy-Disease control rate (DCR)(1 year)
Long term survival follow up(15 years)

研究者

发起方

Peking University

申办方类型

Other

责任方

Principal Investigator

主要研究者

Shen Lin

Professor

Peking University

研究点 (3)

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