Relapsed/Refractory Primary Small-Cell Lung Cancer
Conditions
Interventions
First Dose Cohort:Administer 5.0×10^5 CAR-T cells/kg (+/-20%) based on body weight. If safety is acceptable (no DLT occurring within 28 days after cell infusion), proceed to Dose Level 2
if a DLT occurs, increase the number of enrolled participants and transition to the traditional "3+3" dose escalation design. The same escalation approach will be applied from Dose Level 2 to Dose Lev
Second Dose Cohort:Infusion of 1.0×10^6 CAR-T cells per kilogram of body weight (+/- 20%)
Third Dose Cohort:Administer 3.0×10^6 CAR-T cells/kg (+/-20%) based on body weight.
Dose escalation will be conducted using the conventional "3+3" design, starting from dose level 3.
1. Initially, 3 e
(2) If >=2 out of 3 participants experience DLT, de-escalate to the previous dose level (if the current dose is the lowest, terminate the trial)
(3) If 1 out of 3 participants experiences DLT, enroll an additional 3 participants in the same dose level (total n=6) for further evaluation.
1) If only 1 out of 6 participants experiences D
2) If >=2 out of 6 participants experience DLT (i.e., >=2/6), de-escalate to the previous dose level (if the current dose is the lowest, terminate the trial).
2. When de-escalating to a previous dose
(2) If the previous dose level already has 6 participants enrolled, terminate the trial, and define this dose as the maximum tolerated dose (MTD).
Fourth Dose Cohort:Infusion
Sponsors
Eastern Theater Command General Hospital of the Chinese People's Liberation Army (Jinling Hospital, Affiliated to Nanjing University Medical School)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Willing and able to communicate with the investigators, understand and comply with study requirements, voluntarily participate in the study, and provide written informed consent (Informed Consent Form, ICF), and be willing and able to adhere to visit schedules, dosing regimens, laboratory tests, and other clinical study procedures. 2. Age between 18 and 75 years (inclusive of 18 and 75), either sex. 3. ECOG performance status of 0 or 1. 4. Expected survival time >= 12 weeks. 5. Confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC) by histopathological or cytological examination. 6. Patients who have failed or are intolerant to prior standard therapies, and have no other effective treatment options available. *Intolerance is defined as drug-related adverse reactions or side effects from systemic therapy (including but not limited to targeted therapy or immunotherapy) that prevent continued treatment. 7. Must provide a qualified tumor tissue sample prior to enrollment, or be willing to undergo a tumor biopsy. The tumor tissue sample must test positive for DLL3 by immunohistochemistry (IHC). 8. At least one measurable target lesion according to RECIST v1.1 criteria. 9. Bone marrow function must meet the following criteria (no transfusion of platelets or red blood cells, and no use of thrombopoietin [TPO], granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-11, or other corrective agents within 14 days prior to screening): (1) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; (2) Absolute lymphocyte count (ALC) >= 0.5 × 10^9/L; (3) Platelet count (PLT) >= 75 × 10^9/L; (4) Hemoglobin (HGB) >= 90 g/L. 10. Liver and kidney function must be essentially normal, defined as: (1) Serum creatinine (Cr) = 60 mL/min, calculated by the Cockcroft-Gault formula; (2) Alanine aminotransferase (ALT) <= 2 × ULN (<5 × ULN in patients with liver metastases); aspartate aminotransferase (AST) <= 2 × ULN (<5 × ULN in patients with liver metastases); (3) Total bilirubin (TBil) <= 1.5 × ULN. 11. Coagulation function must be essentially normal, defined as: (1) Prothrombin time (PT) <= 1.5 × ULN; (2) International normalized ratio (INR) <= 1.5 × ULN; (3) Activated partial thromboplastin time (APTT) <= 1.5 × ULN. 12. Capable of establishing adequate venous access for apheresis, with no contraindications to leukapheresis. 13. For female participants of childbearing potential or male participants whose partners are of childbearing potential: Must agree to abstain from sexual activity or use effective contraception (including but not limited to intrauterine devices) from the time of signing the ICF until at least 6 months after cell infusion. Note: Female participants who have undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined as absence of menstruation for more than 12 consecutive months without medical cause) are considered not to have childbearing potential.
Exclusion criteria
Exclusion criteria: 1. Female participants who are pregnant or lactating, or who have a positive baseline serum pregnancy test. 2. Participants with a history of severe allergic reaction to any drug or its components used in this study. 3. Participants who received any investigational drug within 28 days prior to cell infusion, or who are currently enrolled in another clinical trial (excluded: participants enrolled in observational, non-interventional studies, or those in the follow-up phase of an interventional clinical trial). 4. Participants with a history of other known malignancies within the past 5 years, except for previously cured localized tumors such as cervical carcinoma in situ, basal cell carcinoma of the skin, and prostate carcinoma in situ. 5. Participants with any active autoimmune disease or history of autoimmune disease, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, autoimmune hepatitis, interstitial lung disease, inflammatory bowel disease, antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, multiple sclerosis, or glomerulonephritis; or those requiring long-term immunosuppressive therapy. Exclusions: participants with vitiligo or alopecia, any chronic dermatological condition not requiring systemic treatment, or other conditions deemed clinically insignificant by the investigator. 6. Participants with clinically significant thyroid dysfunction, as determined by the investigator (serum free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH] measurements should be performed; total thyroxine [TT4] and total triiodothyronine [TT3] may be assessed if necessary), and deemed unsuitable for enrollment; participants with thyroid function stabilized by treatment may be considered for inclusion. 7. Participants with a history of immunodeficiency, including positive human immunodeficiency virus (HIV) testing, or other acquired or congenital immunodeficiency disorders. 8. Participants with a history of grade =3 thromboembolic events within the past 6 months (including but not limited to pulmonary embolism, main portal vein thrombosis, or deep vein thrombosis of the lower extremities), or those currently receiving thrombolytic or anticoagulant therapy due to high thrombotic risk. 9. Participants with clinically significant cardiovascular disease or symptoms, including: (1) Congestive heart failure (New York Heart Association [NYHA] class >2) within the past year; (2) History of unstable angina within the past year; (3) Myocardial infarction within the past year; (4) Clinically significant malignant arrhythmias (excluding atrial fibrillation or paroxysmal supraventricular tachycardia); (5) Clinically significant QTcF prolongation (male QTcF >450 msec or female QTcF >470 msec); (6) Uncontrolled hypertension despite optimal medical therapy within the past month (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg). 10. Clinically significant ascites, defined as ascites requiring non-pharmacological intervention (e.g., paracentesis) for symptom control within the 3 months prior to apheresis. Participants receiving stable-dose diuretics for ascites for =2 months prior to apheresis are eligible. 11. Uncontrolled pleural effusion or pericardial effusion within 3 months prior to apheresis, requiring repeated drainage procedures (monthly or more frequently). 12. Cancer-related spinal cord compression, leptomeningeal disease, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of DLT or the attainment of MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| The incidence of all adverse events and serious adverse events, and their association with the study product and leukapheresis.;Efficacy endpoints (including ORR, DOR, PFS, and OS assessed according to RECIST v1.1);Clinical PK endpoints: Expansion and persistence of TC-D101 in peripheral blood, assessed by flow cytometry and qPCR.; | — |
Countries
China
Contacts
Public ContactLv Tangfeng
Eastern Theater Command General Hospital of the Chinese People's Liberation Army (Jinling Hospital, Affiliated to Nanjing University Medical School)
Outcome results
None listed