U87 CART in Treatment of Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This is a single center, open-label, phase 1 study to evaluate the safety and efficacy of U87 CART in treating advanced Pancreatic Cancer.

Detailed Description
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Following consent, patients must have tumor tissue evaluated by IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (U87). Following manufacture of the drug product, subjects will receive preconditioning prior to U87 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

Official Title
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Clinical Study to Evaluate the Safety and Efficacy of U87 CART in Treatment of Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: U87 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary informed consent is given; Age 18 to 75; Patients with pathologically confirmed advanced pancreatic cancer who have failed first-line therapy; or patients who are intolerant to first-line standard therapy and voluntarily give up standard therapy; Immunohistochemical (IHC) staining of tumor tissue samples from patients was positive for U87 specific antigen (≥ 2 +, and the expression rate was ≥ 20%); Expected survival ≥12 weeks; Measurable tumor lesions according to RECIST 1.1; ECOG performance score 0-1; Sufficient venous access for mononuclear cell collection; HBc Ab positive, HBsAg negative can be included in the group when the PCR detection of HBV DNA is negative; Patients should maintain adequate organ function; Dyspnea (CTCAE v5.0) ≤ Grade 1; Blood oxygen saturation>91% without oxygen inhalation; Pregnancy test was negative in women of childbearing age; Both male and female subjects should agree to use effective contraceptives during the treatment period and within the following year; Exclusion Criteria: Pregnant or lactating women; Uncontrolled active infections; Active Syphilis, HIV, hepatitis B or hepatitis C infection; Congenital immunodeficiency; Have serious allergic reaction to any drug to be used in this study; Other incurable malignant tumors in the past three years; History or presence of clinically relevant CNS pathology such as epilepsy, Cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease; Have undergone cardiac angioplasty or stent implantation within 12 months, or have a history of myocardial infarction, unstable angina or other clinically significant heart diseases; Subjects requiring anticoagulation or long-term antiplatelet therapy; Subjects who have undergone major surgery or significant trauma within four weeks before enrolled in the study. Other situations that the investigator thinks are not suitable for participating in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: U87 CAR-T cells<br>The Patients are enrolled into 2 dose level cohorts in sequence | Drug: U87 CAR-T<br>* Subjects will be pretreated with cyclophosphamide 250 500 mg/m2( body surface area) for 3 days prior to Intratumoral injection of U87, followed by intraartery of U87 14 days later with intravenous IL-2. This study will explore two dose of dose 1 (DL-1): 1×106 (±20%) to dose 2 (DL-2): 1×107 (±20%),each group was enrolled in 3 6 patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability] | Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Dose-limiting toxicity after U87 CAR-T cells infusion. | 28 days post administration of CAR-T-cells | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness] | Disease control rate: including CR, PR and SD(Assessed based on RECIST 1.1 criteria) | 2 years post CAR T cell infusion | 
| Objective response rate (ORR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness] | Objective response rate includes：CR、PR(Assessed based on RECIST1.1 criteria) | 2 years post CAR T cell infusion | 
| Duration of Response (DOR) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness] | DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause | 2 years post CAR T cell infusion | 
| Progress-free survival(PFS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness] | PFS will be assessed from the first U87 CAR-T cells infusion to death from any cause or the first assessment of progression(Assessed based on RECIST1.1 ） criteria) | 2 years post CAR T cell infusion | 
| Overall survival(OS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness] | OS will be assessed from the first U87 CAR-T cells infusion to death from any cause (Assessed based on RECIST 1.1 criteria) | 2 years post CAR T cell infusion | 
| Pharmacokinetics of U87 CAR-T cells | Peak value of eripheral blood (Cmax) | 2 years post CAR T cell infusion | 
| Pharmacokinetics of U87 CAR-T cells | Area under the eripheral blood concentration versus time curve (AUC) | 2 years post CAR T cell infusion | 
| Pharmacokinetics of U87 CAR-T cells | Time of peak value | 2 years post CAR T cell infusion | 
| Pharmacodynamics of U87 CAR-T cells | Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, IL-2, TNFα, ferritin and CRP at each time point | 2 years post CAR T cell infusion |