Clinical trial NCT05779917: Mesothelin/GPC3/GUCY2C-CAR-T Cells Against Cancers
Official title: Mesothelin/GPC3/GUCY2C Targeted CAR-T for Immunotherapy of Pancreatic Cancer: Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreas Cancer
CAR-T Cell Therapy
Mesothelin
Solid Tumor, Adult
Keywords: Pancreas Cancer
CAR-T
Mesothelin
Solid Tumor
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Fapon Biotherapy Inc.
First posted: 2023-03-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Use engineered CAR-T cells to kill cancer cells with mesothelin overexpression.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

-

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. -

Primary outcomes:
measure: Number of Patients with Dose Limiting Toxicity
timeFrame: six months
Secondary outcomes:
measure: Percent of Patients with best response as either complete remission or partial remission.
timeFrame: six months
measure: Median CAR-T cell persistence
timeFrame: Six years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Zhenfeng Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: