Relapsed/Refractory Small Cell Lung Cancer
Conditions
Interventions
Dose escalation Treatment group 1: GC511B CAR T-Cells a dose levels of DL1 ,Single IV infusion.
Dose escalation Treatment group 2: GC511B CAR T-Cells a dose levels of DL2,Single IV infusion
Dose escalation Treatment group 3:GC511B CAR T-Cells a dose levels of DL3,Single IV infusion
Dose escalation Treatment group 4:GC511B CAR T-Cells a dose levels of DL4,Single IV infusion
Dose expansion cohort 1:GC511B CAR T-Cells a dose levels of specific DL,Single IV infusion
Dose expansion cohort 2:GC511B CAR T-Cells a dose levels of specific DL,Single IV infusion
Dose expansion cohort 3:GC511B CAR T-Cells a dose levels of specific DL,Single IV infusion
Dose expansion cohort 4:GC511B CAR T-Cells a dose levels of specific DL,Single IV infusion
Sponsors
CancerCancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Age 1. Subjects must be >=18 years old at the time of signing the ICF;Subject type and disease characteristics; 2. ECOG performance status score of 0-2; 3. Expected survival of at least 12 weeks; 4. At least one target lesion (TL) meeting RECIST v1.1 criteria at baseline. Tumor assessment by CT scan or MRI must be performed within 28 days prior to single sampling; (1) Lesions previously treated with radiotherapy can be considered TL if they have clear boundaries, are measurable according to RECIST v1.1, and show clear progression during or after the most recent treatment; (2) If a fresh biopsy sample is to be obtained from a tumor lesion during the screening period, that lesion should not be selected as a TL unless imaging is performed at least approximately 2 weeks after the biopsy to allow for healing. Caution should be exercised when obtaining biopsy tissue during treatment if there is only one measurable TL; 5. Availability of archived or representative tumor material for assessing DLL3 expression; 6. Good organ function: (1) Hematologic function: 1) Hemoglobin >= 9 g/dL (no blood transfusion or erythropoietin treatment within 2 weeks prior to screening); 2) Absolute neutrophil count >= 1.5×10^9/L and absolute lymphocyte count >= 0.6×10^9/L (no G-CSF use within 2 weeks prior to screening); 3) Platelet count >= 75×10^9/L (no platelet transfusion or recombinant human thrombopoietin within 2 weeks prior to screening); (2) Liver function (based on normal values defined by the clinical research center): 1) Serum total bilirubin (TBL) = 60 mL/min calculated by the Cockcroft-Gault formula, or creatinine clearance >= 60 mL/min calculated from a 24-hour urine collection; 2) Urine protein = (value missing) on baseline urine dipstick, a 24-hour urine collection must be performed, and the total protein in 24 hours must be = 50%; 7. Ability to establish a venous access and, according to the investigator's judgment, suitable for PBMC collection; 8. Women of childbearing potential must not be breastfeeding, and women of childbearing potential must have a negative high-sensitivity serum pregnancy test result during screening; 9. All subjects of childbearing potential (including women of childbearing potential and men with partners) must agree to use medically acceptable highly effective contraception measures as described in Appendix G throughout the treatment period and for 2 years after the last CAR-T product infusion, or until CAR copy testing is negative (whichever occurs later); 10. Male subjects must agree not to donate sperm, and female subjects must agree not to donate oocytes throughout the treatment period and for 2 years after the last CAR-T product infusion, or until CAR copy testing is negative (whichever occurs later); 11. Able to sign the ICF (as described in Appendix A), including complying with the ICF and the requirements and restrictions listed in this protocol; 12. Subjects have pro
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Female subjects who are pregnant or breastfeeding, or female subjects who test positive for pregnancy during the screening period (women who are not of childbearing potential do not need pregnancy testing, such as those who have had a hysterectomy and/or bilateral oophorectomy, or menopause for >=12 months); 2. Subjects who have received a live vaccine within 4 weeks before leukapheresis or plan to receive any vaccine during the study period (excluding COVID-19 vaccines); 3. Subjects with a history of other acquired or congenital immunodeficiency diseases; subjects who have undergone organ or bone marrow transplantation; 4. Subjects who have experienced severe arterial/venous thromboembolic events or cerebrovascular accidents within 6 months prior to leukapheresis, such as deep vein thrombosis (excluding asymptomatic untreated muscular vein thrombosis), pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, angina, etc.; asymptomatic lacunar cerebral infarction that does not require clinical intervention is excluded; 5. Subjects with hereditary or acquired bleeding or thrombotic tendencies (such as hemophilia, coagulation disorders, splenomegaly); subjects currently receiving thrombolytic or anticoagulant therapy; subjects requiring continuous antiplatelet therapy; 6. Subjects with a QTc interval >450 ms (male) or >470 ms (female) during screening; subjects with a family or personal history of long or short QT syndrome; subjects with a clinically significant history of ventricular arrhythmias, or currently receiving antiarrhythmic drugs, or have an implanted defibrillator for arrhythmia treatment; 7. Subjects with other diseases that may seriously endanger the safety of subjects or affect the completion of the trial, such as peptic ulcer, intestinal obstruction, intestinal paralysis, pulmonary fibrosis, renal failure, uncontrolled diabetes, etc.; 8. Subjects with active or ongoing infections requiring systemic treatment (subjects may begin study treatment 2 weeks after completing anti-infective treatment); 9. Any history of autoimmune nervous system diseases, including but not limited to: multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy. Other active autoimmune or inflammatory diseases, including but not limited to inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, autoimmune hyperthyroidism (Graves' disease), or rheumatoid arthritis. Exceptions to this criterion are as follows: (1) Subjects with vitiligo or autoimmune alopecia; (2) Subjects with autoimmune hypothyroidism (e.g., post-Hashimoto's thyroiditis) whose condition is stable with hormone replacement therapy; (3) Any chronic inflammatory or autoimmune skin disease that does not require systemic treatment; (4) Subjects without active disease in the past 5 years may enroll in this study, but must first consult with the investigator; (5) Subjects with celiac disease that can be controlled solely through dietary management; 10. Subjects known to have life-threatening hypersensitivity reactions or intolerance to cyclophosphamide or fludarabine, or with severe allergic constitution; subjects allergic to human serum albumin, dimethyl sulfoxide, etc.; 11. Active or chronic infectious diseases, including: (1) HBV infe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity (DLT) Rate;Adverse Events (AEs);changes in vital signs, laboratory values, physical examinations ,EGC to baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| Calculate the CK parameters of GC511B, including but not limited to Tmax, Cmax, Tlast, Clast, AUClast, and AUC0-28d ;Evaluate the Replication-competent lentivirus(RCL) in peripheral blood;Objective Response Rate (ORR);Best Overall Response (BOR);Duration of Response (DoR);Disease Control Rate (DCR);Time to Response (TTR);Percentage change in tumor size;Progression Free Survival(PFS);Overall Survival (OS);Quantify the expression level of DLL3 via immunohistochemistry (IHC) ; | — |
Countries
China
Contacts
Public ContactNing Li
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed