Mesothelin-CAR-T Cells Against Cancers

Sponsor

Second Affiliated Hospital of Guangzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05779917

Collaborator

Fapon Biotherapy Inc. (Other)

Enrollment

Location

120

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreas Cancer CAR-T Cell Therapy Mesothelin Solid Tumor, Adult	Biological: CAR-T cells	Phase 1

Detailed Description

Choose appropriate patients with advanced pancreatic cancer or other cancers, with written consent for this study;
Perform biopsy to determine the expression of Mesothelin of the tumors by western blotting or IHC;
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;
To enhance the killing capability, cotreatment the patients with PD1/PDL1/CTLA4 antibodies may be applied;
Evaluate the clinical results as needed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Use engineered CAR-T cells to kill cancer cells with mesothelin overexpression.Use engineered CAR-T cells to kill cancer cells with mesothelin overexpression.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 10, 2023

Anticipated Primary Completion Date :

Mar 10, 2026

Anticipated Study Completion Date :

Mar 10, 2033

Outcome Measures

Primary Outcome Measures

Number of Patients with Dose Limiting Toxicity [six months]
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.

Secondary Outcome Measures

Percent of Patients with best response as either complete remission or partial remission. [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.
Median CAR-T cell persistence [Six years]
Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

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. -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong	China	510260

Sponsors and Collaborators

Second Affiliated Hospital of Guangzhou Medical University
Fapon Biotherapy Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Second Affiliated Hospital of Guangzhou Medical University

ClinicalTrials.gov Identifier:

NCT05779917

Other Study ID Numbers:

FC004

First Posted:

Mar 22, 2023

Last Update Posted:

Mar 22, 2023

Last Verified:

Mar 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Second Affiliated Hospital of Guangzhou Medical University

Additional relevant MeSH terms:

Pancreatic Neoplasms

Study Results

No Results Posted as of Mar 22, 2023