Clinical Trial: NCT03198052 - My Cancer Genome

NCT03198052

Description:

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.

Related Conditions:

Cancer

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03198052

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: CAR-T on lung cancer
NCT ID: NCT03198052

Conditions

Lung Cancer
Cancer
Immunotherapy
CAR-T Cell

Interventions

Drug	Synonyms	Arms
CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3	Administration of CAR-T cells through vein or interventional technique.	CAR-T cell therapy group

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
CAR-T cell therapy group	Experimental	Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.	CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3

Eligibility 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. -

Maximum Eligible Age:	75 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Number of Patients with Dose Limiting Toxicity
Time Frame:	three months
Safety Issue:
Description:	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

Measure:	Percent of Patients with best response as either complete remission or partial remission.
Time Frame:	three months
Safety Issue:
Description:	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.

Measure:	Median CAR-T cell persistence
Time Frame:	Six years
Safety Issue:
Description:	Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Second Affiliated Hospital of Guangzhou Medical University

Trial Keywords

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

Last Updated

December 1, 2020

Clinical Trials /

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