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

Pancreas Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05779917
• Other study ID #: ZZFC004CAR-018
• Status: Recruiting
• Phase: Phase 1
• Start date: March 10, 2023
• Est. completion date: March 10, 2033

Study information

• Verified date: March 2023
• Source: Second Affiliated Hospital of Guangzhou Medical University
• Contact: Zhenfeng Zhang, MD, PhD
• Phone: 0086-020-39195965
• Email: zhangzhf[@]gzhmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 10, 2033
• Est. primary completion date: March 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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. -

Related Conditions & MeSH terms

• CAR-T Cell Therapy
• Pancreas Cancer
• Pancreatic Neoplasms
• Solid Tumor, Adult

Intervention

Biological:
• CAR-T cells
Transfer CAR-T cells into patients for anti-ancer therapy.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University	Fapon Biotherapy Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Median CAR-T cell persistence	Median CAR-T cell persistence will be measured by quantitative rt-PCR.	Six years