U87 CART in Treatment of Advanced Solid Tumor

Pancreatic Cancer Clinical Trial

Official title:

Clinical Study to Evaluate the Safety and Efficacy of U87 CART in Treatment of Advanced Solid Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05605197
• Other study ID #: U87-3
• Status: Recruiting
• Phase: Phase 1
• Start date: October 19, 2022
• Est. completion date: October 8, 2025

Study information

• Verified date: November 2023
• Source: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Contact: Maoquan Li, doctor
• Phone: 021-66300114*3506
• Email: cjr.limaoquan[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, open-label, phase 1 study to evaluate the safety and efficacy of U87 CART in treating advanced solid tumor .

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: October 8, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Voluntary informed consent is given;

2. Age 18 to 75;

3. Patients with pathologically confirmed advanced solid tumor who have failed first-line therapy; or patients who are intolerant to first-line standard therapy and voluntarily give up standard therapy;

4. Immunohistochemical (IHC) staining of tumor tissue samples from patients was positive for U87 specific antigen (= 2 +, and the expression rate was = 20%);

5. Expected survival =12 weeks;

6. Measurable tumor lesions according to RECIST 1.1;

7. ECOG performance score 0-1;

8. Sufficient venous access for mononuclear cell collection;

9. HBc Ab positive, HBsAg negative can be included in the group when the PCR detection of HBV DNA is negative;

10. Patients should maintain adequate organ function;

11. Dyspnea (CTCAE v5.0) = Grade 1; Blood oxygen saturation>91% without oxygen inhalation;

12. 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:

1. Pregnant or lactating women;

2. Uncontrolled active infections;

3. Active Syphilis, HIV, hepatitis B or hepatitis C infection;

4. Congenital immunodeficiency;

5. Have serious allergic reaction to any drug to be used in this study;

6. Other incurable malignant tumors in the past three years;

7. History or presence of clinically relevant CNS pathology such as epilepsy, Cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease;

8. 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;

9. Subjects requiring anticoagulation or long-term antiplatelet therapy;

10. Subjects who have undergone major surgery or significant trauma within four weeks before enrolled in the study.

11. Other situations that the investigator thinks are not suitable for participating in this study.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Solid Tumor, Adult

Intervention

Drug:
• U87 CAR-T
Subjects will be pretreated with cyclophosphamide 250~500 mg/m2( body surface area) for 3 days prior to Intravenous injection of U87, followed by intraartery of U87 14 days later with intravenous IL-2. Researchers can perform intratumoral injection based on their judgment.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.

Locations

Country	Name	City	State
China	China Shanghai 10th People's Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd	Shanghai 10th People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease control rate (DCR) of U87 CAR-T cells treatment in advanced solid tumor. [Effectiveness]	Disease control rate: including CR, PR and SD(Assessed based on RECIST 1.1 criteria)	2 years post CAR T cell infusion
Secondary	Objective response rate (ORR) of U87 CAR-T cells treatment in advanced solid tumor. [Effectiveness]	Objective response rate includes:CR?PR(Assessed based on RECIST1.1 criteria)	2 years post CAR T cell infusion
Secondary	Duration of Response (DOR) of U87 CAR-T cells treatment in advanced solid tumot[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
Secondary	Progress-free survival(PFS) of U87 CAR-T cells treatment in advanced solid tumor[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
Secondary	Overall survival(OS) of U87 CAR-T cells treatment in advanced solid tumor [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
Secondary	Pharmacokinetics of U87 CAR-T cells	Peak value of eripheral blood (Cmax)	2 years post CAR T cell infusion
Secondary	Pharmacokinetics of U87 CAR-T cells	Area under the eripheral blood concentration versus time curve (AUC)	2 years post CAR T cell infusion
Secondary	Pharmacokinetics of U87 CAR-T cells	Time of peak value	2 years post CAR T cell infusion
Secondary	Pharmacodynamics of U87 CAR-T cells	Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN ?, IL-2, TNFa, ferritin and CRP at each time point	2 years post CAR T cell infusion