Advanced solid tumors
Conditions
Interventions
Treatment:CAR-T cells
Sponsors
Shanghai Tenth People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: (1) Patients must have a histological or cytological diagnosis of advanced solid tumors, such as ovarian cancer, hepatobiliary cancer and colorectal cancer; (2) Patients must have failed established standard medical anti-cancer therapies; (3) 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; (4) Life expectancy > 3 months; (5) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (6) Subjects must meet blood coagulation parameters and have adequate venous peripheral access for apheresis. Patients must also have adequate mononuclear cells for CAR T cell manufacturing; (7) Staining of MSLN must be greater than 50% of the cells in the tumor tissue and with apparent expression in the membrane. PD-L1 expression must be positive. Tissue obtained for the biopsy must be = 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; b. Total bilirubin must be less than or equal to two times (= 60ml/min/1.73m2 [eGFR=186 *(age)-0.203 * SCr-1.154(mg/dl)* 0.742 for female]; d. International normalized ratio (INR) or the PT is not greater than one and one half times (= 91% f. Cardiac function: cardiac ejection fraction (LVEF) must be greater than fifty percent (>=50%) by echocardiogram or MUGA one month before enrollment. (9) Subjects must have measureable disease as defined by RECIST 1.1 criteria; (10) Subjects sufficiently understand the trial and willingly sign the informed consent; (11) For concurrent medication: a. Systemic therapeutic corticosteroids must be stopped 72 hours before CAR-T infusion. However, patients using physiologic replacement doses of corticosteroids, or its equivalent, will be considered eligible; b. Immunosuppressive therapy must be stopped within four (4) weeks prior to enrollment; (12) 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
Exclusion criteria: (1) Prior therapy with targeted therapy or cell therapy against MSLN; (2) Prior therapy with anti-PD-1 agents; (3) Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad; (4) Active bacteria, viral or fungal infection, and not contained after anti-infective therapy (positive results in the blood = 3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically significant heart disease; (8) 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; (9) Patient has a history or current evidence of any condition such as neurotic, psychiatric, immune, metabolic and infectious disease, on any therapy, or laboratory abnormality that might confound the results of the study, interfere with the patients participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator. (10) Patient has a known history of a hematologic malignancy, or of another malignant primary solid tumor concurrently, with the exception of : a. Patients with in situ cervical cancer or breast cancer with no evidence of disease for >= 3 years after curative treatments; b. Patients who underwent successful definitive resection of in situ cancer with no evidence of disease for >= 5 years; (11) Has had chemotherapy, radioactive, small molecules, biological cancer therapy, immunotherapy or other investigational drugs within 4 weeks prior to the initiation of the study; (12) Pregnant or breastfeeding women; (13) Investigators think that patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patients participation for the full duration of the study and cooperation with the requirements of the trial, uncontrolled medical, psychological, familial, sociological, or geographical conditions, or is not in the best interest of the patient to participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate;Clinical response;Progression-free survival;Overall survival;Pharmacokinetics of aPD1-MSLN-CAR T cells;Pharmacodynamics of aPD1-MSLN-CAR T cells; | — |
Countries
China
Contacts
Public ContactQing Xu
Shanghai Tenth People's Hospital
Outcome results
None listed