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 sites in 1 country134 target enrollmentMarch 26, 2019

ConditionsAdvanced Solid Tumor

InterventionsCAR-CLDN18.2 T-Cells PD-1 Monoclonal Antibody Chemotherapy

DrugsCAR-CLDN18.2 T-Cells PD-1 Monoclonal Antibody Chemotherapy

Overview

Phase: Phase 1
Intervention: CAR-CLDN18.2 T-Cells
Conditions: Advanced Solid Tumor
Sponsor: Peking University
Enrollment: 134
Locations: 3
Primary Endpoint: Dose-limiting toxicity (DLT)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

March 26, 2019

End Date

January 26, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Peking University

Responsible Party

Principal Investigator

Shen Lin

Professor

Peking University

Eligibility Criteria

Inclusion Criteria

•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；

Exclusion Criteria

•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)；