Autologous T-cells engineered to express CARs targeting Mesothelin and Claudin18.2, for Unresectable locally advanced or metastatic pancreatic adenocarcinoma (Pancreatic Ductal Adenocarcinoma, PDAC), administered as two separate sequential infusions following lymphodepleting chemotherapy
Expected survival time ≥3 months;
Histologically or cytologically confirmed pancreatic adenocarcinoma that is advanced (unresectable or metastatic). Patients should have received, or be intolerant of, standard first-line therapy (e.g., gemcitabine/nab-paclitaxel, FOLFIRINOX) for advanced disease. A short course of current first-line therapy is allowed for the purpose of bridging to manufacturing, but evidence of disease progression on or after at least one line is required prior to infusion (for the dose-expansion phase, patients must have progressed on ≥1 prior systemic regimen).
ECOG Performance Status: 0 or 1 (fully active or restricted in strenuous activity but ambulatory).
Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
Single group
Mesothelin and Claudin 18.2 CAR-T cells
Biological/VaccineThe intervention in this clinical trial involves a novel approach using Mesothelin and Claudin 18.2 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. Mesothelin and Claudin 18.2 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, Mesothelin and Claudin 18.2 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial Mesothelin and Claudin 18.2 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.
Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells
Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.
Rate of successful manufacture and expansion of the Mesothelin and Claudin 18.2 chimeric antigen receptor (CAR) T cells
satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)
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