U87 CART in Treatment of Advanced Solid Tumor

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

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

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Solid Tumor, Adult
• Intervention / Treatment: Drug: U87 CAR-T

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maoquan Li, doctor; Phone Number: 021-66300114*3506; Email: cjr.limaoquan@vip.163.com
• Study Contact Backup: Name: Shilong Han, doctor; Phone Number: 021-66303247

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • China Shanghai 10th People's Hospital
    • Contact: Li mao quan, doctor; Phone Number: 3506 021-66300114; Email: cjr.limaoquan@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: U87 CAR-T cells; The Patients are enrolled into 2 dose level cohorts in sequence

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.

What is the study measuring?

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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Collaborators: Shanghai 10th People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): October 8, 2025

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 29, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: U87-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No