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Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

Primary Purpose

Liver Cancer, Lung Cancer, Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
Sponsored by
Second Affiliated Hospital of Guangzhou Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring liver Cancer, Lung Cancer, Solid Tumor, TIL, CAR-TIL, PD1, CTLA4, GPC3, Mesothelin, B7-H3, CRISPRA-CAS9

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TILs/CAR-TILs treatment

Arm Description

Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.

Outcomes

Primary Outcome Measures

Safety of TILs/CAR-TILs treatment in advanced solid cancers
Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

Secondary Outcome Measures

Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers
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.

Full Information

First Posted
April 4, 2021
Last Updated
February 26, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
Collaborators
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04842812
Brief Title
Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
January 1, 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Guangzhou Medical University
Collaborators
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Choose appropriate patients with advanced lung or other cancers, with written consent for this study; Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol; 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; 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; Evaluate the clinical results as needed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer, Lung Cancer, Breast Cancer, Colo-rectal Cancer, Brain Tumor, Solid Tumor, Adult, PD1, CTLA4
Keywords
liver Cancer, Lung Cancer, Solid Tumor, TIL, CAR-TIL, PD1, CTLA4, GPC3, Mesothelin, B7-H3, CRISPRA-CAS9

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
TILs treatment of solid cancers
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TILs/CAR-TILs treatment
Arm Type
Experimental
Arm Description
Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.
Intervention Type
Biological
Intervention Name(s)
TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
Intervention Description
TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.
Primary Outcome Measure Information:
Title
Safety of TILs/CAR-TILs treatment in advanced solid cancers
Description
Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame
up to 36 months
Secondary Outcome Measure Information:
Title
Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers
Description
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.
Time Frame
15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced cancers that failed to current available therapies; Life expectancy >12 weeks; Adequate heart, lung, liver, kidney functions; Available for tumor biopsy or cancerous effusions; Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. Exclusion Criteria: Had accepted gene therapy before; Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity; Active infectious disease related to bacteria, virus, fungi, et al; Other severe diseases that the investigators consider not appropriate; Pregnant or lactating women; Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day); Other conditions that the investigators consider not appropriate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhenfeng Zhang, MD, PhD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Bingjia He, MD
Phone
+862039195965
Email
464677938@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PhD
Organizational Affiliation
Second Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Second Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
ZIP/Postal Code
510260
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PhD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Bingjia He
Phone
+862039195965
Email
464677938@qq.com
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PHD
First Name & Middle Initial & Last Name & Degree
Peng Li, PHD

12. IPD Sharing Statement

Plan to Share IPD
No

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Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

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