An Exploratory Study on the Treatment of Advanced Solid Tumors by Secretory PD1 Nanoantibody Targeting Mesothelin Fast CAR T Cells

Shanghai Cell Therapy Group Co.,Ltd1 site in 1 country12 target enrollmentJune 1, 2023

ConditionsSolid Tumor

Overview

Phase: Early Phase 1
Intervention: Not specified
Conditions: Solid Tumor
Sponsor: Shanghai Cell Therapy Group Co.,Ltd
Enrollment: 12
Locations: 1
Primary Endpoint: Dose-limiting toxicity(DLT)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of fast autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies in patients with solid tumors.

Detailed Description

The main aim of this study is to determin the safety and efficacy of BZT2312 in patients with solid tumors. BZT2312 is an autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies. This study comprises of a screening phase(less than or equal to 28 days prior to apheresis) followed by apheresis(will occur upon enroiiment); Apheresis phase(less than or equal to 10 days prior to infusion ) followed by lymphodepletion. lymphodepletion phase (from day -5 to day -3) followed by infusion.Treatment Phase including infusion of BZT2312 on Day0 and then post-infusion assessments from Day1 to Day 28; and a Post-treatment Phase(Day 29 and up to end of the study). Efficacy will be explored to assessed and safety will be closely monitored during the study.

Registry

clinicaltrials.gov

Start Date

June 1, 2023

End Date

December 31, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Cell Therapy Group Co.,Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients diagnosed with advanced solid tumors through histopathological diagnosis have a positive rate of ≥ 50% for mesothelin expression membrane in tumor tissue samples, PD-L1 positive expression, and sample sources 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:
•absolute neutrophil count must be greater than ≥ 1.5×109/L, lymphocyte count must be greater than ≥ 0.5×109/L, platelets must be greater than ≥ 90×109/L, hemoglobin must be greater than ≥ 90g/L without transfusion within 7 days or dependency on EPO;
•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);
•International normalized ratio (INR) or the PT is not greater than one and one half times (≤ 1.5) the upper limit of normal;
•Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%

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;
•Patients who are allergic to BZT2312 components;
•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;