MSLN-positive advanced malignant solid tumor
Conditions
Interventions
Intervention group:MSLN STAR-T cell infusion
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-70 years, no gender limit; 2. Advanced malignant solid tumors confirmed by histology or cytology, including malignant mesothelioma (pleura, peritoneum, etc.), pancreatic cancer, ovarian cancer, intrahepatic bile duct cancer, lung cancer, gastric cancer, colorectal cancer, etc.; 3. Patients with advanced malignant solid tumor who relapse after systematic treatment or cannot tolerate existing treatment, including but not limited to: (1) Patients with malignant mesothelioma who have previously received at least first-line treatment failure; (2) Patients with pancreatic cancer who had previously failed at least first-line therapy; (3) Gastric cancer patients who had failed at least second-line treatment; (4) Ovarian cancer patients who had received at least second-line platinum-sensitive or platinum-resistant treatment in the past; (5) Patients with intrahepatic cholangiocarcinoma who had received at least first-line treatment failure; (6) Patients with advanced non-small cell lung cancer (non-squamous cell carcinoma) : patients with EGFR, ALK, ROS1, MET and other driver genes positive who developed disease progression or intolerance after targeted therapy; Patients with negative EGFR, ALK, ROS1, MET and other driver genes developed disease progression or intolerance after receiving >=1 line therapy; (7) Patients with colorectal cancer who had failed at least second-line treatment in the past; 4. Mesenchymal (MSLN) was positive in tumor tissue samples (>10% by IHC detection); 5. During screening, there were measurable target lesions on imaging (according to RECIST1.1), with the length diameter of non-lymph node lesions >=1.0cm or the short diameter of lymph node lesions >=1.5cm; 6. ECOG score 0-1; 7. Expected survival >=3 months; 8. Having the conditions to establish the peripheral blood mononuclear cell collection pathway and having enough cells to prepare STAR-T cells; 9. Good bone marrow and organ function: (1) Blood routine: absolute neutrophil count (ANC) >=1.5x10^9/L; Hemoglobin (Hb) >=85g/L; Platelet count >=75x10^9/L; (2) Blood biochemistry: total bilirubin (TBIL) = 91% in non-oxygenated state; 10. Patients of childbearing age must undergo serological pregnancy tests during the screening period and the results are negative; And willing to use a reliable method of contraception during the trial and 24 months after the cell infusion; Male patients whose partners are women of reproductive age should be surgically sterilized or agree to use a reliable method of contraception during the trial period and for 24 months after cell transfusion; 11. The patients voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
Exclusion criteria: 1. There are active infected persons who are difficult to control during screening; Meet one of the following criteria: Hepatitis B surface antigen (HBsAg) positive and/or Hepatitis Be antigen (HBeAg) positive, Hepatitis Be antibody (HBe-Ab) and/or Hepatitis B core antibody (HCB-AB) positive and HBV-DNA copy number greater than the lower limit, hepatitis C antibody (HCV-Ab) positive and HCV-RNA copy number greater than the lower limit, human immunodeficiency virus (HIV) antibody positive, treponema pallidum (TP-Ab) antibody positive; 2. Patients with or with a history of central nervous system diseases, such as epilepsy, stroke, severe brain injury, aphasia, paralysis, etc.; 3. Patients with active BMS who did not require any radiation, surgery, or steroid therapy to control metastatic symptoms 1 month before screening were enrolled; 4. Systemic lupus erythematosus, combined with active or uncontrolled autoimmune diseases (such as Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.); 5. Currently receiving therapeutic dose or systemic corticosteroid therapy (prednisone >=20mg/ day or equivalent dose of other corticosteroids); 6. Toxicity or complications caused by previous intervention or treatment do not return to CTCAE v5.0<=2 or below (except for hair loss and laboratory test outliers judged by the investigator as not clinically significant); 7. Previously received other genetically modified T cell products (such as MSLN CAR T or TCR-T cells), or targeted MSLN therapy; 8. Patients who have received any of the following medications or treatments during a specified time before apheresis: (1) Received any chemotherapy within 2 weeks prior to anemiculture or within 5 half-lives, whichever is shorter; (2) Received any large or small molecule targeted therapy, such as monoclonal antibody, antibody-coupled drug (ADC), or double antibody, within 4 weeks or 5 half-lives, whichever is shorter; (3) Patients who had received radiotherapy within 6 weeks prior to anapheresis were allowed to be included if the disease progressed at the radiotherapy site or if there were positive lesions such as CT images at other sites without radiotherapy; If there were positive lesions on CT and other images in other sites without radiotherapy, radiotherapy was allowed for a single lesion 2 weeks before monocele; 9. There is uncontrolled pleural effusion, pericardial effusion or ascites (ascites defined as: ascites with positive signs of ascites on physical examination or ascites requiring intervention (only those with ascites shown on imaging without intervention can be included); 10. Other malignancies were diagnosed within 3 years prior to screening, except for treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ; 11. Other serious medical conditions that may limit participants' participation in the study. Examples include poorly controlled diabetes, left ventricular ejection fraction (LVEF) <50%, New York Heart Association (NYHA) heart function Class III or IV heart failure; Myocardial infarction, unstable arrhythmia, or unstable angina within 6 months; History of pulmonary embolism within 1 year; Moderate or above chronic obstructive pulmonary disease, interstitial lung disease (except radiologically insignificant interstitial changes), and clinically significant abnormalities in lung function; Or gastrointestinal bleeding of clinical significance; 12.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity;Maximum tolerated dose;Adverse event; | — |
Countries
China
Contacts
Public ContactShen Lin
Outcome results
None listed