Mesothelin-positive advanced solid tumors
Conditions
Interventions
Group 1:Chemotherapy pretreatment + GC503 cells (1-2x10^6 CAR+ T/kg)
Group 2:Chemotherapy pretreatment + GC503 cells (5-10x10^6 CAR+ T/kg)
Group 3:Chemotherapy pretreatment + GC503 cells (2.5-5.0x10^7 CAR+ T/kg)
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged 18-70 years (including critical value); 2. Patients diagnosed with locally advanced or metastatic malignant solid tumors by pathological examination have received at least one standard treatment regimen, and their disease is in a stable or progressive state, and they refuse to undergo subsequent chemotherapy of anti-tumor therapy; 3. Freshly punctured tumor tissue (if the patient has not received targeted mesothelin therapy, the previous tumor pathological tissue can be used), and the positive rate of mesothelin expression in the tumor cell membrane is confirmed by immunohistochemistry >= 10%; 4. Expected survival period >= 90 days; 5. ECOG score =10mm, and short diameter of malignant lymph node >=15mm; 8. Female patients of childbearing age must be in non-breastfeeding period, and the high-sensitivity serum pregnancy test during the screening period of fertile females must be negative. All patients must use medically approved contraceptive measures (such as intrauterine devices, contraceptives) throughout the treatment period and within 1 year after cell reinfusion, and male patients should also avoid sperm donation; 9. The organ function and bone marrow reserve status are good, and the following requirements must be met within 14 days before the screening without receiving blood transfusion, not using granulocyte colony-stimulating factor (G-CSF) treatment, and not using drugs to correct: (1) The absolute value of neutrophils is >= 1.5x10^9/L; (2) The absolute value of lymphocytes >= 0.8x10^9/L; (3) Platelet count >= 75x10^9/L; (4) Hemoglobin >= 9 g/dl; (5) Total bilirubin value 60ml/min; male creatinine clearance rate=[(140-age)xbody weight (kg)]/[0.818xcreatinine (umol/L)]; female creatinine clearance rate = [(140-age) x body weight (kg) x 0.85]/[0.818 x creatinine (umol/L)]; (8) Blood urea nitrogen = 3g/dl; (10) Stable coagulation function: prothrombin time (PT) = 55%, no moderate or more pericardial effusion; (13) Under the indoor air environment, the basic finger saturation is more than 92%; 10. Intravenous access can be established, and peripheral blood mononuclear cell collection can be performed according to the judgment of the investigator; 11. Voluntarily sign the informed consent; 12. The patient can communicate well with the researcher, is willing and able to comply with the research plan, and complete the research in accordance with the research regulations.
Exclusion criteria
Exclusion criteria: 1. Patients with moderate or more moderate pleural and ascites requiring puncture or catheter drainage to relieve symptoms; pericardial effusion with clinical symptoms; 2. Positive for hepatitis B surface antigen (HBsAg); positive for hepatitis B core antibody (HBcAb) and positive for HBV DNA copy number; positive for hepatitis C antibody (HCV-Ab); anti-Treponema pallidum antibody (TP-Ab) positive; Human immunodeficiency virus antibody (HIV-Ab) positive; meet any one of them; 3. Suffering from other malignant tumors, except for the following cases: cured non-melanoma skin cancer, cervical cancer in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, and other malignant tumors with disease-free survival of more than 5 years; 4. Active central nervous system invasion; 5. Received CNS-directed radiotherapy within 28 days before enrollment; 6. Have received bone marrow transplantation, stem cell transplantation or organ transplantation in the past; 7. Previously received targeted mesothelin therapy or CAR-T therapy or other gene editing T cell therapy; 8. Patients whose last antitumor therapy was less than 7 days before enrollment; 9. Participated in other clinical studies within 28 days before enrollment; 10. Received vaccination within 28 days before enrollment; 11. According to the investigator's judgment, there are comorbidities that require the use of systemic corticosteroid treatment or other immunosuppressive drug treatment during the study period; 12. Acute toxic and side effects caused by previous treatment have not recovered to grade 1 or below (except for hematological toxicity and alopecia); 13. Known to have life-threatening hypersensitivity reaction or other intolerance to cyclophosphamide or fludarabine or severe allergic constitution; hypersensitivity constitution, allergic to human serum albumin, DMSO, etc.; 14. Have received major surgery under general anesthesia within 28 days before enrollment, or have not recovered from previous surgical treatment and achieved clinical stability, or are expected to need major surgery under general anesthesia during the study; 15. Suffering from any unstable circulatory system disease within 180 days before enrollment, including but not limited to unstable angina pectoris, myocardial infarction, heart failure [New York Heart Association (NYHA) classification >= grade III], severe cardiac arrhythmia requiring medical treatment, or cardiac angioplasty or coronary stenting or heart bypass surgery within 180 days prior to enrollment; 16. Presence or history of central nervous system disease, such as epilepsy, cerebral ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the CNS; 17. Uncontrollable active infection (including but not limited to bacteria, fungi, viruses, tuberculosis, etc.) at the time of screening; 18. Active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sj?gren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except for hypothyroidism that can be controlled only by hormone replacement therapy); 19. Hemorrhagic and thrombotic tendency: have clinically significant bleeding symptoms or a clear bleeding tendency within 90 days before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.; hereditary or acquired bleeding and thrombotic tendency (such as hemophilia,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;Adverse event;Real-time fluorescent quantitative PCR method to detect the proliferation level, duration and infiltration of GC503 in peripheral blood, pleural effusion/ascites/pericardial effusion (if applicable) (such as PK parameters such as Cmax, Tmax, AUC of GC503);Flow cytometry to detect the proliferation level, duration, and infiltration of GC503 in peripheral blood, pleural effusion/ascites/pericardial effusion (if applicable) (such as GC503's Cmax, Tmax, AUC and other PK parameters); | — |
Secondary
| Measure | Time frame |
|---|---|
| Replication-type lentivirus (RCL) detection;Disease control rate (DCR);Duration of remission (DOR);Progression-free survival (PFS);Overall survival (OS);Incidence of GC503 antibody production in peripheral blood; | — |
Countries
China
Contacts
Public ContactZhang Yi
Outcome results
None listed