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Chimeric Antigen Receptor T Cells Targeting claudin18.2 in Solid Tumors.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03874897
Recruitment Status : Not yet recruiting
First Posted : March 14, 2019
Last Update Posted : March 19, 2019
CARsgen Pharmaceuticals Co.,Ltd
Information provided by (Responsible Party):
Shen Lin, Peking University

Brief Summary:
An open label, dose escalating/dose regimen finding clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: CAR-CLDN18.2 T-Cells Phase 1

Detailed Description:
This study is an open, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Lable, Dose Escalating/Dose Regimen Finding 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
Estimated Study Start Date : March 20, 2019
Estimated Primary Completion Date : March 20, 2020
Estimated Study Completion Date : March 20, 2021

Arm Intervention/treatment
Experimental: CAR-CLDN18.2 T-Cells
The subjects enrolled will be sequentially assigned to the corresponding dose level.
Drug: CAR-CLDN18.2 T-Cells

Pretreatment with fludarabine, cyclophosphamide,

• Chimeric Antigen Receptor T Cells Targeting Claudin18.2

Other Name: Chimeric Antigen Receptor T Cells Targeting Claudin18.2

Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) [ Time Frame: 28 days of single infusion ]

  2. Maximum tolerated dose (MTD) [ Time Frame: 28 days of single infusion ]

Secondary Outcome Measures :
  1. Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood) [ Time Frame: 26 weeks ]
    CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after infusion

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 1 year ]
    Adverse events occurring through 26 weeks and 12 months post infusion of CAR-CLDN18.2 T-Cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.

  3. Antitumor efficacy-Progression-free survival (PFS) [ Time Frame: 1 year ]
    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.

  4. Antitumor efficacy-Duration of response (DOR) [ Time Frame: 1 year ]
    The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause

  5. Antitumor efficacy-Duration of disease control (DDC) [ Time Frame: 1 year ]
    The period from the first evaluation of clinical benefit to the first evaluation of PD or any cause of death.

  6. Antitumor efficacy-Overall survival (OS) [ Time Frame: 2 years ]
    The period from the first infusion to any cause of death

  7. Antitumor efficacy-Objective response rate (ORR) [ Time Frame: 1 year ]
    The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation

  8. Antitumor efficacy-Disease control rate (DCR) [ Time Frame: 1 year ]
    The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged 18 to 75 years, male or female;
  2. Subjects with pathologically confirmed solid tumors (ie, advanced gastric cancer, esophagogastric junction cancer, and pancreatic cancer) and have been failed to standard systemic treatment;
  3. Tumor tissue samples was positive for claudin 18.2 IHC staining;
  4. Estimated life expectancy > 12 weeks;
  5. According to the RECIST 1.1, there is at least one target lesion, defined as: the longest diameter of the non-lymph node is ≥10 mm, or the shortest perpendicular diameter of the lymph node is ≥15 mm;
  6. ECOG physical status score 0 ~ 1;
  7. Sufficient venous access for mononuclear cell collection (abbreviation: apheresis)
  8. Subjects should have adequate organ functions before screening and pre-treatment (at baseline).
  9. Female subjects of childbearing age must undergo a serum pregnancy test at screening and prior to pretreatment 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);
  10. 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:

  1. Pregnant or lactating women;
  2. HIV, Treponema pallidum or HCV serologically positive;
  3. Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection (HBsAg positive, or HBcAb positive and HBV DNA positive);
  4. 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;
  5. The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and other tolerable events determined by investigator;
  6. Subjects who are using steroids systemically currently; those using inhaled steroids recently or currently are not excluded;
  7. Allergic to immunotherapy and related drugs, history of severe allergies or allergies to components of CT041CAR-CLDN18.2T injection, allergic to β-lactam antibiotics;
  8. Previously received any chimeric antigen receptor-modified T-cells (CAR-T) or cellular immunotherapy.
  9. Subjects have untreated or symptomatic brain metastases;
  10. Subjects have central or extensively metastases in lung.
  11. Subjects have extensive metastases in liver
  12. Subjects have heart disease eg. Uncontrolled hypertension after treatment (blood pressure > 160 mmHg / 100 mmHg) ;
  13. Subjects with unstable or active ulcers and gastrointestinal bleeding currently;
  14. Subjects with a history of organ transplantation or awaiting organ transplantation;
  15. Subjects requiring anticoagulant therapy or continuous anti-platelet therapy;
  16. 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;
  17. There are no other serious diseases that may limit subjects' participation in this trial
  18. The investigator assessed that the subject was unable or unwilling to comply with the requirements of the study protocol.
  19. Before the baseline and pre-treatment, the ECOG physical status score is >1 point;
  20. Blood oxygen saturation ≤ 95% before pre-treatment (accept finger oxygen detection method);
  21. Prior to pretreatment, 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;
  22. The subject has a central nervous system disease sign or an abnormal neurological test result with clinical significance;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03874897

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Contact: Lin Shen 861088196561
Contact: Jifang Gong 861088196561

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China, Beijing
Department of GI Oncology, Peking University Cancer Hospital
Beijing, Beijing, China, 100142
Sponsors and Collaborators
Peking University
CARsgen Pharmaceuticals Co.,Ltd
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Principal Investigator: Lin Shen Beijing Cancer Hospital

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Responsible Party: Shen Lin, Professor, Peking University Identifier: NCT03874897     History of Changes
Other Study ID Numbers: CT041-CG4006
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shen Lin, Peking University:
Advanced solid tumor
CAR-T cell therapy