Recurrent ovarian epithelial cancer
Conditions
Interventions
Experimental group:FC004 (MSLN-directed CAR-T cells)
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects should meet all of the following criteria: 1. Voluntarily joined the study, have signed the informed consent, and with good compliance; 2. Ovarian epithelial cancer confirmed by histology; 3. The expression intensity of mesothelin was higher than 2+ or the positive rate of tumor cells was over 40%; 4. Treatment failure or recurrence of disease after receiving second-line or above standard treatment; 5. Age 18-75; 6. Have at least one measurable lesion according to RECIST 1.1 criteria; 7. American Eastern Collaboration Group (ECOG) score 0-2; 8. Expected to survive for more than 3 months; 9. Major organ function is normal, that is, meet the following criteria: Neutrophil absolute value count >= 1.5×10^9/L, lymphocyte absolute value >= 0.5×10^9/L, platelet >= 50×10^9/L, hemoglobin >= 80 g/L, Aspartate transferase (AST) and alanine transferase (ALT) <=2.5 times the upper limit of normal (UNL) (<=5.0×ULN is acceptable if abnormal liver function is due to malignant metastasis), total bilirubin < 1.5×UNL, serum creatinine < 1.5×UNL; 10. Subjects with potential fertility need to use at least one medically approved contraceptive method (such as an IUD, contraceptive pill or condom) during the study treatment period (screening period to 12 months after cell transfusion treatment); Serum/urine HCG test must be negative before the first dose; And must be non-lactating.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded in this study: 1. Participants in other clinical trials within 28 days before the first dose; 2. Have previously received other cell therapies such as CAR-T/ TCRT /TIL or are allergic or intolerant to therapeutic drugs (including chemotherapy preconditioning drugs and tocilizumab), or are allergic to excipients of cell therapy products; 3. Have active autoimmune diseases requiring systemic treatment within 2 years prior to the first dosing, or autoimmune diseases that the investigator determines are likely to recur or are planned for treatment. The following are excluded: skin diseases that do not require systematic treatment (e.g. vitiligo, alopecia, psoriasis or eczema); Hypothyroidism due to autoimmune thyroiditis requires only stable dose hormone replacement therapy; Type 1 diabetes requiring only steady dose of insulin replacement therapy; Asthma has been completely relieved in childhood, and no intervention is required in adulthood; The researchers judged that the disease would not recur in the absence of external triggers; 4. Subjects requiring systemic treatment with corticosteroids (>10mg/ day equivalent dose of prednisone) or other immunosuppressive drugs within 14 days prior to the first dosing. The following exceptions: If there is no active autoimmune disease, treatment with inhaled, ophthalmic, or topical corticosteroids or other corticosteroids at doses not exceeding 10mg/ day of prednisone or equivalent is permitted. 5. Received anti-tumor therapy such as surgery, chemotherapy, radiotherapy, immunotherapy, and biotherapy within 28 days before the first dose (except endocrine therapy); Has not fully recovered from toxicity and/or complications caused by antitumor therapy, i.e. = 450 ms for men and 470 ms for women) occurred within 6 months before the first dose (QTc interval Fridericia) Formula calculation); New York Heart Association (NYHA) heart function grade > II or left ventricular ejection fraction (LVEF) = 500 IU/ml; Or HCV antibody positive and HCV virus copy number > upper limit of normal) or syphilis; 12. Have another malignant tumor that is currently progressing, or has received effective anti-tumor therapy within the past 3 years (except for various cancers in situ [such as breast, bladder, cervical carcinoma in situ] or skin basal cell or squamous cell carcinoma that has been treated with potentially curable therapy); 13. Have a history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 14. Have a history of immunodeficiency, including HIV testing positive, or have other acquired or congenital immunodeficiency diseases; 15. Received living vaccine 30 days before the first dose; 16. The investigator considers that the subject is not
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities;Adverse events;maximum tolerated dose;RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Overall survival;Pharmacokinetics (including CAR gene copy number and CAR+ peripheral cells));Pharmacodynamics (including tumor biomarkers and cytokines); | — |
Countries
China
Contacts
Public ContactLan Chunyan
Sun Yat-sen University Cancer Center
Outcome results
None listed