Small Cell Lung Cancer
Conditions
Interventions
Group Pre-A: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 5x10e5/kg
Group Pre-A: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 1x10e6/kg
Group Pre-A: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 1.5x10e6/kg
Group A: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 2x10e6/kg
Group B: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 5x10e6/kg
Group C: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, Dose: 7.5x10e6/kg
Dose expansion Group: CAR-T Cell + Bridging radiotherapy:Intravenous inject CAR-T cells, using the recommended dose
Dose expansion Group: CAR-T Cell :Intravenous inject CAR-T cells, using the recommended dose
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Patients with recurrent or refractory small cell lung cancer (SCLC) confirmed by histology or cytology who have relapsed or progressed after treatment with one previous platinum-based regimen; 2. Patients can provide sufficient tumor tissue (fresh or paraffin sections, etc.); 3. Age 18 ~70 (including boundary), for both men and women; 4. ECOG performance status of 0-1; 5. Life expectancy >=3 months; 6. At least one extracranial measurable lesion (RECIST v1.1) exists;for lesion after radiotherapy, must be confirmed that the lesion has progressed ; 7. Patients in limited-stage at the initial diagnosis must undergo radical thoracic radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or radical thoracic dose radiotherapy cannot be performed for specific reasons; 8. Patients with brain metastasis can be included if treated and are stable and meet the following conditions: (1) Treatment was completed for at least 2 weeks before PBMCs collection, without imaging CNS progression; (2) Patients with CNS disease must be asymptomatic for more than 7 days or more (unless the investigator determines that the symptoms are irreversible), and antiepileptic drugs for the treatment of malignant CNS must be discontinued for at least 7 days (but stable doses are allowed); (3) Radiation therapy for brain metastases must be no less than 3 months before the end of radiotherapy. 9. Adequate hematologic and organ function, as defined by the following laboratory findings: (1) Absolute neutrophil count (ANC)>=1.5x10^9/ L (1500 / µL) (no treatment with granulocyte colony stimulating factor); (2) Lymphocyte count>=0.5×10^9/L(500 /µL); (3) Platelet count =100×109/L(100000 /µL)(in the absence of blood transfusion); (4) Hemoglobin >=90g/L(9.0g/dL); (5) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)<= 2.5× upper limit of normal (ULN), with the following exceptions: 1) Patients with confirmed liver metastasis: AST and ALT <=5× ULN; 2) Patients with confirmed liver or bone metastases: ALP<= 5 ×ULN; (6) Total bilirubin:<=1.5×ULN; (7) Creatinine clearance=60 mL/min (calculated using the Cockcroft-Gault formula); (8) For patients not on anticoagulation: International normalized ratio (INR) and activated partial thromboplastin time (aPTT) <=1.5×ULN. 10. For patients receiving anticoagulation therapy: a stable anticoagulation regimen; 11. The test results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C and syphilis were negative at screening; 12. Female patients or male reproductive age patients and their partners should agree to effective contraception from sighing ICF to 6 months after the last BHP01 infusion.
Exclusion criteria
Exclusion criteria: 1. Patients with known primary CNS tumor, or meningeal metastasis, or patients with unstable CNS metastasis (symptomatic, requiring hormonal therapy within 4 weeks before investigational treatment, or no radiographic evidence of stabilization of the lesion for more than 4 weeks); 2. Received major surgical procedures (except for diagnosis) within 4 weeks before PBMCs collection, or are expected to require major surgical procedures during the study; 3. Received Chinese herbal medicine or Chinese patent medicine for anti-tumor indications within 7 days before PBMCs collection; 4. Patients with a history of idiopathic pulmonary fibrosis, mechanical pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia or idiopathic pneumonia, or evidence of active pneumonia by chest computer tomography (CT) at screening [a history of radiation pneumonia (fibrosis) in the irradiated field may participate in this study]; 5. Poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage procedures (once a month or more frequently); 6. Poorly controlled or symptomatic hypercalcemia (ionic calcium> 1.5 mmol/L, calcium> 12 mg/dL or corrected calcium> ULN); 7. Presence of active or previous autoimmune diseases or immunodeficiencies, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, etc.; 8. Severe infection within 4 weeks before the start of PBMCs collection, including but not limited to hospitalization due to infection, bacteremia, severe pneumonia, or any active infection that may affect the patient's safety; 9. Serious cardiovascular and cerebrovascular diseases (such as heart disease =New York Heart Association class II, myocardial infarction or cerebrovascular accident), unstable arrhythmia or unstable angina pectoris within 3 months before PBMCs collection; 10. Treatment with any other anticancer drug or systemic immunostimulant (including but not limited to interferon and interleukin-2 [IL-2]) within 4 weeks prior to PBMCs collection or within 5 drug elimination half-lives (whichever is longer) ; 11. Use of systemic immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-inhibitors) within 2 weeks prior to peripheral apheresis, or anticipated need for systemic immunosuppressive medications during study treatment, with exceptions in the following cases: (1) Patients receiving short-term, low-dose systemic immunosuppressive drugs or one-time pulse therapy with systemic immunosuppressive drugs (e. g. 48 hours of corticosteroids for contrast allergic reactions) may be eligible for the study after confirmation by the medical monitor (2) Patients who received mineralocorticoids (e. g. flunandrocortisone), inhaled or low dose corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low dose corticosteroids for orthostatic hypotension or adrenal insufficiency were eligible for the study 12. Previous treatment with DLL 3 target drugs or CAR-T or other gene-modified T cells; 13. Received any other Investigational drug within 28 days prior to PBMCs collection; 14. A history of mental illness; 15. Incapacitated persons or persons with limited capacity; 16. pregnant or lactating females; Males or females who are unwilling to use adequate contraception; Females of childbearing potential are required to undergo a pregnancy study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR);Progression-free survival (PFS);Disease control rate (DCR);Duration of response (DoR); PFS rate at 6 month and 1 year;Overall survival (OS);OS rate at 1 year and 2 year; | — |
Countries
China
Contacts
Public ContactYou Lu
West China Hospital, Sichuan University
Outcome results
None listed