Mesothelin/GPC3/GUCY2C-CAR-T Cells Against Cancers

Mesothelin/GPC3/GUCY2C Targeted CAR-T for Immunotherapy of Pancreatic Cancer: Phase I Clinical Trial

The second generation of mesothelin targeted CAR-T cells that secret a fusion protein of IL21 and scfv against PD1 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-T cells for immunotherapy of human cancer patients with Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the Mesothelin-CAR-T cell immunotherapy on human cancers will firstly be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Pancreas Cancer; Solid Tumor, Adult; CAR-T Cell Therapy; Mesothelin
• Intervention / Treatment: Biological: CAR-T cells

Detailed Description

1. Choose appropriate patients with advanced pancreatic cancer or other cancers, with written consent for this study;
2. Perform biopsy to determine the expression of Mesothelin of the tumors 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 Mesothelin 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 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: Zhenfeng Zhang, MD, PHD; Phone Number: +862039195966; Email: zhangzhf@gzhmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with advanced cancer that expresses 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 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

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 Mesothelin-CAR T 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
Median CAR-T cell persistence	Median CAR-T cell persistence will be measured by quantitative rt-PCR.	Six years
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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Collaborators: Fapon Biotherapy Inc.
• Investigators: Principal Investigator: Zhenfeng Zhang, MD, PhD, Second Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Estimated): March 10, 2026
• Study Completion (Estimated): March 10, 2033

Study Registration Dates

• First Submitted: March 10, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 11, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: CAR-T; Solid Tumor; Pancreas Cancer; Mesothelin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: ZZFC004CAR-018

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