在实体瘤中靶向 claudin18.2 的嵌合抗原受体 T 细胞。

计划状态

招聘

阶段

第 1 阶段

允许先接受免疫治疗

没有

CRC 指导的试验

没有

药物

CAR-CLDN18.2 T-Cells, Chemotherapy, PD-1 Monoclonal Antibody

标签

MSI-H/ MMRd、MSS/ MMRp
地点 位置状态
中国
Department of GI Oncology, Peking University Cancer Hospital
北京, 北京 100142
招聘
郑州大学第一附属医院
河南郑州 450052
招聘
The First Affiliated Hospital , Zhejiang University School of Medicine
Hangzhou, Zhejiang 310006
招聘

联系方式

Lin Shen
联系方式
861088196561 linshenpku@163.com
Jifang Gong
联系方式
861088196561 goodjf@163.com

纳入标准

纳入标准

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

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.

NCT ID

NCT03874897

添加审判日期

2019-03-14

更新日期

2022-03-14