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HER2/Mesothelin/Lewis-Y/PSCA/MUC1/GPC3/AXL/EGFR/B7-H3/Claudin18.2-CAR-T Cells Immunotherapy Against Cancers

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ClinicalTrials.gov Identifier: NCT03198052
Recruitment Status : Recruiting
First Posted : June 23, 2017
Last Update Posted : December 1, 2020
Sponsor:
Collaborators:
Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

Brief Summary:
The third generation of CAR-T cells that target HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, or B7-H3 have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, or B7-H3 expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the HER2/Mesothelin/Lewis-Y/PSCA/MUC1/GPC3/AXL/EGFR/B7-H3 -CAR-T cell immunotherapy on human cancers will firstly be tested.

Condition or disease Intervention/treatment Phase
Lung Cancer Cancer Immunotherapy CAR-T Cell Biological: CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 Phase 1

Detailed Description:
  1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study;
  2. Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 of the tumor by western blotting or IHC;
  3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed;
  4. To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3-DAP10-CAR with knockdown of PD1/HPK1;
  5. Other cancers with these cell surface antigen expressions are also recruited if needed;
  6. Evaluate the clinical results as needed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Use engineered CAR-T cells to kill cancer cells with certain targets.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CAR-T Cells Targeting HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, B7-H3 or Claudin18.2 for Immunotherapy of Lung Cancer: Phase I Clinical Trial
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : August 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CAR-T cell therapy group
Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.
Biological: CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3
CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.
Other Name: Administration of CAR-T cells through vein or interventional technique.




Primary Outcome Measures :
  1. Number of Patients with Dose Limiting Toxicity [ Time Frame: three months ]
    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the PSCA/MUC1/GPC3/AXL/EGFR/B7-H3 -CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.


Secondary Outcome Measures :
  1. Percent of Patients with best response as either complete remission or partial remission. [ Time Frame: three months ]
    Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

  2. Median CAR-T cell persistence [ Time Frame: Six years ]
    Median CAR-T cell persistence will be measured by quantitative rt-PCR.



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
Criteria

Inclusion Criteria:

1. Patients with advanced cancer that expresses PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 protein; 2. Life expectancy >12 weeks; 3. Adequate heart,lung,liver,kidney function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 CAR determined by flow-cytometry and killing of PSCA,MUC1,GPC3, AXL, EGFR, or B7-H3 -positive targets greater than or equal to 20% in cytotoxicity assay; 5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

-

Exclusion Criteria:

  1. Had accepted gene therapy before;
  2. Severe virus infection such as HBV,HCV,HIV,et al;
  3. Known HIV positivity;
  4. Active infectious disease related to bacteria, virus,fungi,et al;
  5. Other severe diseases that the investigators consider not appropriate;
  6. Pregnant or lactating women;
  7. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);
  8. Other conditions that the investigators consider not appropriate. -

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 ClinicalTrials.gov identifier (NCT number): NCT03198052


Contacts
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Contact: Zhenfeng Zhang, MD,PhD 0086-020-34153532 zhangzhf@gzhmu.edu.cn
Contact: Peng Li, PhD +86 20 32015300 lipeng@invivobio.com.cn

Locations
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China, Guangdong
The First Affiliated Hospital of Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510072
Contact: Xianhong Xiang, MD,PHD         
Contact: Yonghui Huang, MD,PHD         
The Second Affiliated Hospital of Guangzhou Medical University Recruiting
Guangzhou, Guangdong, China, 510260
Contact: Zhenfeng Zhang, MD,PhD       zhangzhf@gzhmu.edu.cn   
Contact: Deji Chen, MD,PhD    +86-020-34153532    chendeji2003@163.com   
Sponsors and Collaborators
Second Affiliated Hospital of Guangzhou Medical University
Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
Investigators
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Principal Investigator: Zhenfeng Zhang, MD,PhD Second Affiliated Hospital of Guangzhou Medical University
Publications of Results:
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Responsible Party: Second Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT03198052    
Other Study ID Numbers: CAR-T on lung cancer
First Posted: June 23, 2017    Key Record Dates
Last Update Posted: December 1, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Second Affiliated Hospital of Guangzhou Medical University:
Lung Cancer
CAR-T Cell Therapy
PSCA
MUC1
HER2
Mesothelin
Lewis-Y
GPC3
AXL
EGFR
B7-H3
Claudin18.2
TGFβ
DAP10
HPK1
PD1
CTLA4
Tigit
Knockdown
SCFV
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases