GPC3/Mesothelin-CAR-γδT Cells Against Cancers

June 22, 2024 updated by: Second Affiliated Hospital of Guangzhou Medical University

GPC3/Mesothelin Targeted CAR-γδT for Immunotherapy of Solid Cancer: Phase I Clinical Trial

The third generation of GPC3/mesothelin targeted CAR-γδT cells have been constructed and their anti-cancer function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test anti-cancer function of the CAR-γδT cells for immunotherapy of human cancer patients with GPC3 or Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin-CAR-γδT cell immunotherapy on human cancers will firstly be evaluated.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  1. Choose appropriate patients with advanced solid cancers, with written consent for this study;
  2. Perform biopsy to determine the expression of GPC3 or Mesothelin of the tumors by western blotting or IHC;
  3. Collect blood from the patients and isolate mononuclear cells, select and grow γδT cells and transfect the γδT cells with GPC3 or Mesothelin targeting CAR, amplify the transfected γδT cells as needed, test the quality and killing activity of the CAR-γδT cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as required;
  4. To enhance the killing capability, cotreatment the patients with PD1/PDL1/CTLA4 antibodies may be applied;
  5. Evaluate the clinical results as needed.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510260
        • Recruiting
        • The Second Affiliated Hospital of Guangzhou Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

1. Patients with advanced cancer that expresses GPC3 or Mesothelin protein; 2. Life expectancy >12 weeks; 3. Adequate heart, lung, liver, kidney, and blood function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of GPC3/Mesothelin-CAR determined by flow-cytometry and killing of Mesothelin-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. -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: γδT cell therapy for solid tumor
Biological: Cell therapy for solid tumors
Transfer γδT cells into patients for anti-ancer therapy.
Experimental: CAR-γδT cell therapy for solid tumor
Biological: Cell therapy for solid tumors
Transfer γδT cells into patients for anti-ancer therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients with Dose Limiting Toxicity
Time Frame: Six months
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the γδT cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
Six months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Patients with best response as either complete remission or partial remission.
Time Frame: Six 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.
Six months
Median γδT cell persistence
Time Frame: Six years
Median γδT cell persistence will be measured by quantitative rt-PCR.
Six years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Investigators

  • Principal Investigator: Zhenfeng Zhang, MD, PhD, Second Affiliated Hospital of Guangzhou Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2024

Primary Completion (Estimated)

November 30, 2030

Study Completion (Estimated)

December 30, 2036

Study Registration Dates

First Submitted

December 22, 2023

First Submitted That Met QC Criteria

January 6, 2024

First Posted (Actual)

January 9, 2024

Study Record Updates

Last Update Posted (Actual)

June 26, 2024

Last Update Submitted That Met QC Criteria

June 22, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZZCAR-γδT-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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