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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fast CAR T cells | Experimental | Pretreatment was given 5 days before CAR T infusion for 3 consecutive days, and CAR T cell infusion was performed on the 0th day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fast CAR T cells | Biological | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity(DLT) | Safety | After 28 days of infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) | Tolerability | After 28 days of infusion |
| Objective response rate (ORR) | Clinical response will be assessed by RECIST 1.1 |
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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:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yong Xia | Contact | 021-67091399 | xiay@shcell.com |
| Name | Affiliation | Role |
|---|---|---|
| Jinxing Lou | Shanghai Mengchao Cancer Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Mengchao Cancer Hospital | Recruiting | Shanghai | Shanghai Municipality | China |
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| 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 |
| Peak Plasma Concentration (Cmax) | Pharmacokinetics (PK) | Month 12 |
| AUC | Pharmacokinetics (PK) | Day 28 |
| 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 |