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Engineered TILs/CAR-TILs to Treat Advanced 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.
 
ClinicalTrials.gov Identifier: NCT04842812
Recruitment Status : Recruiting
First Posted : April 13, 2021
Last Update Posted : April 13, 2021
Sponsor:
Collaborator:
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

Brief Summary:
Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

Condition or disease Intervention/treatment Phase
Liver Cancer Lung Cancer Breast Cancer Colo-rectal Cancer Brain Tumor Solid Tumor, Adult PD1 CTLA4 Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, 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 or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;
  3. Grow TILs and engineered the tumor-effective TILs with CRISPRA-CAS9 technique to knockdown PD1 and electronic-transfection strategy to express scFvs that target PD1 and CTLA4; amplify the engineered T cells as needed, test the quality and killing activity of the TILs and then transfuse them back the patients via systemic or local injections via standard protocol, and follow up closely to collect related parameters as needed;
  4. To enhance the killing capability, tumor-noneffective TILs have also been genetically engineered to express various CARs targeting HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3/ROR1/GD2/AXL/Claudin6-DAP10 with knockdown of PD1/HPK1 as appropriate;
  5. Evaluate the clinical results as needed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: TILs treatment of solid cancers
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Engineered TILs/CAR-TILs With PD1 Knockout and Anti-PD1/CTLA4-scFv Secreting or CARs Against Various Antigens to Treat Advanced Solid Tumors
Actual Study Start Date : January 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 1, 2035

Arm Intervention/treatment
Experimental: TILs/CAR-TILs treatment
Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.
Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.




Primary Outcome Measures :
  1. Safety of TILs/CAR-TILs treatment in advanced solid cancers [ Time Frame: up to 36 months ]
    Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.


Secondary Outcome Measures :
  1. Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers [ Time Frame: 15 years ]
    Assessing various clinical response rates including complete response, partial response, stable disease, and progress disease during and after TILs/CAR-TILs treatment in advanced solid cancers.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with advanced cancers that failed to current available therapies;
  2. Life expectancy >12 weeks;
  3. Adequate heart, lung, liver, kidney functions;
  4. Available for tumor biopsy or cancerous effusions;
  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; Known HIV positivity;
  3. Active infectious disease related to bacteria, virus, fungi, et al;
  4. Other severe diseases that the investigators consider not appropriate;
  5. Pregnant or lactating women;
  6. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);
  7. 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): NCT04842812


Contacts
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Contact: Zhenfeng Zhang, MD, PhD +862039195966 zhangzhf@gzhmu.edu.cn
Contact: Bingjia He, MD +862039195965 464677938@qq.com

Locations
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China
Second Affiliated Hospital of Guangzhou Medical University Recruiting
Guangzhou, China, 510260
Contact: Zhenfeng Zhang, MD, PhD    +862039195966    zhangzhf@gzhmu.edu.cn   
Contact: Bingjia He    +862039195965    464677938@qq.com   
Principal Investigator: Zhenfeng Zhang, MD, PHD         
Sub-Investigator: Peng Li, PHD         
Sponsors and Collaborators
Second Affiliated Hospital of Guangzhou Medical University
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
Investigators
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Principal Investigator: Zhenfeng Zhang, MD, PhD Second Affiliated Hospital of Guangzhou Medical University
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Responsible Party: Second Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT04842812    
Other Study ID Numbers: TILs on cancers
First Posted: April 13, 2021    Key Record Dates
Last Update Posted: April 13, 2021
Last Verified: April 2021
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:
liver Cancer
Lung Cancer
Solid Tumor
TIL
CAR-TIL
PD1
CTLA4
GPC3
Mesothelin
B7-H3
CRISPRA-CAS9
Additional relevant MeSH terms:
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Neoplasms
Liver Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases