Non-small cell lung cancer
Conditions
Interventions
experimental group:CAR-T Cell infusion
Sponsors
The First Affiliated Hospital of Nanchang University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily signed informed consent with good compliance and follow-up; 2. Aged between 18 and 75 years, regardless of gender; 3. Patients with advanced, locally advanced, or recurrent metastatic NSCLC confirmed by histology or cytology; 4. Patients who have failed previous standard treatment; Patients with recurrence within 6 months of postoperative chemoradiotherapy; Or patients who give up treatment for various reasons after first-line treatment is ineffective; 5. tumor tissue samples IHC staining Claudin6 Mucin1 / Mesothelin positive; 6. Expected survival > 12 weeks; 7. At least one stably assessed target lesion according to RECIST1.1, defined as: longest diameter of non-lymph node lesion >= 10mm, or short diameter of lymph node lesion >= 15mm; 8. Adequate venous access for mononuclear cell collection (monocapheresis for short) and no contraindications for lymphocyte collection; 9. Physical status score 0-1 in the eastern Tumor cooperative group (ECOG) within 24 hours before single harvest; 10. Subjects should meet the following test results before screening and lymphocyte pretreatment (baseline). If abnormal laboratory tests do not meet the following criteria, they will be allowed to have a reexamination within one week to confirm whether it is due to laboratory error. If they still do not meet the criteria, the screening will be considered as failure: Blood routine (no blood transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) and other supportive treatments should be performed within 7 days before the test) : WBC >= 2.5 x 10^9/L, LY >= 0.5 x 10^9/L, PLT >= 75 x 10^9/L, Hb >= 8.0 g/dL; Blood biochemistry: Endogenous creatinine clearance rate >= 40 mL/min (Cockcroft Gault formula), ALT <= 2.5 x ULN, AST <= 2.5 x ULN, total bilirubin <= 2 x ULN; Serum lipase and amylase < 1.5 ULN; Alkaline phosphatase <= 2.5 ULN; If bone or liver metastasis occurred, AST, ALT and alkaline phosphatase < 5ULN; Prothrombin time (PT) was prolonged <= 4s; 11. Negative pregnancy test for women of childbearing age; Both men and women must agree to use effective contraception during treatment and for one year thereafter.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women; 2. Positive serology of HIV, treponema pallidum or HCV; 3. Any uncontrolled active infection, including but not limited to active tuberculosis, infected with HBV; 4. Clinically significant thyroid dysfunction (serum thyroid hormone measurements TT4, TT3, FT3, FT4 and serum thyroid stimulating hormone TSH) was judged inappropriate for the study; 5. Toxic and side effects caused by previous treatment of the subject have not recovered to CTCAE=1, except for hair loss, pigmentation and other tolerable events judged by the investigator and abnormal laboratory examination permitted by the protocol; 6. Systemic use of glucocorticoids >= 15mg/ day within 7 days prior to monotherapy, and recent or current use of inhaled glucocorticoids were not excluded; 7. Subjects who are allergic or intolerant to fludarabine, cyclophosphamide and albumin paclitaxel or tozizumab, or are allergic to ingredients in CLDN6/MUC1/MSLN CAR T cell infusion preparations, or have previous penicillin allergy confirmed positive by skin test, or have previous history of other severe allergies such as anaphylactic shock; 8. Prior treatment with any genetically engineered T cells other than this product (including CAR T, TCR-T cells, etc.) 9. There are untreated brain metastases or symptoms of brain metastases; 10. Extensive liver metastasis, or extensive bone metastasis; 11. Subjects who have a history of organ transplantation or are waiting for organ transplantation; 12. subjects requiring anticoagulant therapy such as warfarin or heparin; 13. subjects requiring long-term antiplatelet therapy; 14. Subjects who underwent major surgery or significant trauma within 4 weeks prior to monopheresis, or who are expected to require major surgery during the study period; 15. There are other serious medical conditions that may limit subjects' participation in this study, such as: Poorly controlled diabetes (HBA1C > 8% after treatment), poorly controlled hypertension (blood pressure > 160mmHg/100mmHg), severe cardiac dysfunction (left ventricular ejection fraction LVEF < 50%), myocardial infarction or unstable arrhythmia or unstable angina within the last 6 months, Pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, or clinically significant pulmonary function abnormalities; 16. The investigator assessed that the subject was unable or unwilling to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity;Incidence of adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| 3-month complete remission rate;cellular pharmacokinetics;Cellular pharmacodynamics; | — |
Countries
China
Contacts
Public ContactYu Bentong
The First Affiliated Hospital of Nanchang University
Outcome results
None listed