GPC3/Mesothelin-CAR-γδT Cells Against Cancers

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: Lung Cancer; Mesothelioma; Pancreas Cancer; Liver Cancer; Solid Tumor, Adult; CAR-T Cell Therapy
• Intervention / Treatment: Biological: Cell therapy for solid tumors

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

• Study Contact: Name: Zhenfeng Zhang, MD, PhD; Phone Number: 0086-020-39195965; Email: zhangzhf@gzhmu.edu.cn
• Study Contact Backup: Name: Bingjia He, MD; Phone Number: +862039195965; Email: 464677938@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • Recruiting
      • The Second Affiliated Hospital of Guangzhou Medical University
      • Contact: Deji Chen, MD,PhD; Phone Number: +86-020-34153532; Email: chendeji2003@163.com
      • Contact: Zhenfeng Zhang, MD,PhD; Email: zhangzhf@gzhmu.edu.cn

Participation Criteria

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.

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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

How is the study designed?

Design Details

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

Number of Arms

2

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	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.	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	Median γδT cell persistence will be measured by quantitative rt-PCR.	Six years

Collaborators and Investigators

• 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

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: Solid Tumor; Mesothelin; GPC3; γδT; CAR-γδT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenoma; Neoplasms, Mesothelial; Pancreatic Neoplasms; Mesothelioma
• 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