An Exploratory Study by Fast CAR T Cells

Exploratory Study on the Treatment of Advanced Solid Tumor With Non-viral Vector Multi-targeted Autosecretory Multifunctional Antibody CAR-T Cell Injection

The main goal of this trial is to evaluate the safety and tolerability of CAR T cell therapy for advanced solid tumors with positive mesothelin and MUC1.Patients were screened, peripheral blood mononuclear cells (PBMC) were isolated from eligible patients, and cells were prepared. Pretreatment was performed within 5 days before infusion, and CAR T cells were infused on day 0 (the dose was determined according to the requirements of climbing/expansion). The safety intensive observation period was 28 days after infusion, and the clinical efficacy after infusion was evaluated on days 28-34. The follow-up observation and evaluation were carried out according to the follow-up visit point, and the follow-up period was 1 year. From the second year, the telephone follow-up period was entered.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: Fast CAR T cells

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yong Xia; Phone Number: 021-67091399; Email: xiay@shcell.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Mengchao Cancer Hospital
      • Contact: Lou jinxing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with advanced solid tumors through histopathological diagnosis have a positive rate of ≥ 50% for mesothelin expression membrane and ≥ 50% for MUC1 expression in tumor tissue samples. PD-L1 expression is positive, and the sample source is within 2 years；
• Late stage malignant solid tumor patients who have failed standard treatment or are intolerant to such treatment and do not have a standard effective treatment plan ；
• Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
• Life expectancy >3 months；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；

• Satisfactory organ and bone marrow function as defined by the following：

  1. absolute neutrophil count must be greater than ≥ 1.5×10^9/L, lymphocyte count must be greater than ≥ 0.5×10^9/L, platelets must be greater than ≥ 90×10^9/L, hemoglobin must be greater than ≥ 90g/L without transfusion within 7 days or dependency on EPO;
  2. Total bilirubin must be less than or equal to two times (≤2.0x) the institutional normal upper limit; transaminases, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), must be less than or equal to 2.5 times (≤2.5x) the institutional normal upper limit (≤5x if there is hepatic metastasis);
  3. International normalized ratio (INR) or the PT is not greater than one and one half times (≤ 1.5) the upper limit of normal;
  4. Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%；
  5. Cardiac function: cardiac ejection fraction (LVEF) must be greater than fifty percent (≥50%) by echocardiogram or MUGA one month before enrollment.
• Subjects must have measureable disease as defined by RECIST 1.1 criteria;
• Subjects sufficiently understand the trial and willingly sign the informed consent；
• Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for at least 12 months following the last dose of the study cell infusion and until no CAR-T cells can be detected after two consecutive PCR tests.

Exclusion Criteria:

• Subjects who have undergone other anti-tumor treatments (including radiation therapy, chemotherapy, small molecule, biological or immunotherapy, and other study drugs) other than lymphocytes depletion allowed by the protocol within one month prior to CAR-T infusion;
• Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad;
• Pregnant or breastfeeding women;
• Positive serological reactions for HIV and syphilis; Hepatitis B surface antigen positive, hepatitis B core antibody positive, and hepatitis B virus DNA copy number higher than the detection limit and/or greater than or equal to 1000 copies/mL; Or Hepatitis C virus infected individuals;
• Any uncontrollable active infection, coagulation disorders, or any other major illness;
• Patients with autoimmune diseases, organ transplantation and other immune related diseases under treatment, or long-term use of immunosuppressive drugs such as glucocorticoids: a. Glucocorticoids: users cannot stop using CAR-T cells 72 hours before infusion; b. Immunosuppressants other than glucocorticoids cannot be stopped ≥ 4 weeks before enrollment;
• History of severe cardiac or pulmonary disease, including hypertension that cannot be controlled by medication, and any of the conditions occurred within the past 6 months: congestive heart failure (New York Heart Association functional classification ≥3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically significant heart disease;
• Detectable clinically relevant central nervous system (CNS) metastases and/or pathology such as epilepsy/seizure, brain Ischemia/ hemorrhage, dementia, cerebellar disease, or autoimmune disease affecting central nervous system.
• Patients at high risk of causing bleeding or perforation;
• Patients who had undergone major surgical procedures or significant trauma within 4 weeks before apheresis, or who were expected to require major surgery during the study period;
• Patient has a known history of a hematologic malignancy, or of another malignant primary solid tumor concurrently, with the exception of :Patients with in situ cervical cancer or breast cancer with no evidence of disease for ≥ 3 years after curative treatments;Patients who underwent successful definitive resection of in situ cancer with no evidence of disease for ≥5 years;
• Other circumstances that were deemed by the investigator to be inappropriate for trial participation.

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: Fast CAR T cells; Pretreatment was given 5 days before CAR T infusion for 3 consecutive days, and CAR T cell infusion was performed on the 0th day	Biological: Fast CAR T cells; This study designed three dose groups, each with a dosage of 5.0 × 10^5/kg、1.0×10^6/kg、5.0×10^6/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity(DLT)	Safety	After 28 days of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Clinical response will be assessed by RECIST 1.1	Month 12
Peak Plasma Concentration (Cmax)	Pharmacokinetics (PK)	Month 12
Progression-free survival (PFS)	PFS of patients receiving Fast CAR T cells	Month 12
Overall survival (OS)	OS of patients receiving Fast CAR T cells	Month 12
Pharmacodynamics (PD)	D of IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN-γ, TNF-α and MCP1 will be analysed after CAR T cell infusion	Day 28
Maximum tolerated dose (MTD)	Tolerability	After 28 days of infusion
AUC	Pharmacokinetics (PK)	Day 28

Collaborators and Investigators

• Sponsor: Shanghai Cell Therapy Group Co.,Ltd
• Investigators: Principal Investigator: Jinxing Lou, Shanghai Mengchao Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): March 6, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: BZE2203-A-01

Drug and device information, study documents

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