Non-Small Cell Lung Cancer
Conditions
Keywords
Chimeric Antigen Receptor Dendritic Cells, Chimeric Antigen Receptor T-Cells, Non-Small Cell Lung Cancer
Brief summary
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of EphA2-targeted CAR-DC combined with CAR-T cell therapy in patients with non-small cell lung cancer.
Detailed description
Main purpose: To evaluate the safety of EphA2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced non-small cell lung cancer during the dose-escalation phase. To determine the maximum tolerated dose of EphA2-targeted CAR-DCs when administered in combination with CAR-T cells. Secondary purpose: To assess the overall response rate (ORR), including complete response (CR) and partial response (PR), as well as overall survival (OS) and disease-free survival (DFS) in patients receiving the combination therapy. To evaluate the in vivo persistence, immunophenotype, and functional activity of CAR-T cells and CAR-DCs following infusion.
Interventions
BIOLOGICALEphA2-targeted CAR-T Cells
Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2
BIOLOGICALEphA2-targeted CAR-DCs
Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Pathologically confirmed stage IV non-small cell lung cancer (NSCLC) with at least one measurable lesion according to RECIST 1.1 criteria (i.e., a lesion with the longest diameter ≥10 mm on spiral CT scan or a lymph node with a short axis ≥15 mm). 2. Tumor tissue tested positive for EphA2 expression by immunohistochemistry (≥20%). 3. Disease progression after standard treatment or no available standard treatment (patients must have received at least two prior systemic therapies, including but not limited to chemotherapy and immune checkpoint inhibitors; patients with actionable driver mutations must have failed targeted therapy). 4. ECOG performance status: 0-1. 5. Expected survival ≥6 months. 6. Toxicities related to prior anti-tumor treatments must have resolved to baseline levels or ≤ Grade 1 (excluding residual alopecia); Grade ≤2 neurotoxicity is acceptable. Washout periods: 4 weeks for chemotherapy and immunotherapy, 2 weeks for targeted therapy. 7. Adequate organ function, including: * Adequate hematologic function: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥75×10\^9/L, hemoglobin ≥9 g/dL. No transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin allowed within 14 days before blood tests. * Adequate hepatic function: Total bilirubin (TBIL) \<1.5× upper limit of normal (ULN); AST and ALT \<2.5×ULN. For patients with Gilbert's syndrome, TBIL \<2×ULN; if liver metastases are present, AST and ALT \<5×ULN. * Adequate renal function: Serum creatinine (Cr) ≤1.5×ULN, or if Cr \>1.5×ULN, creatinine clearance (CrCl) ≥60 mL/min calculated using the Cockcroft-Gault formula. * Adequate coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) \<1.5×ULN; international normalized ratio (INR) \<1.5 or within the target range if on anticoagulant therapy. 8. Subjects of reproductive potential must be willing to use effective contraception. 9. Ability to understand and voluntarily sign the informed consent form. 10. Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria
1. Pathologically confirmed mixed histology, such as adenosquamous carcinoma of the lung. 2. Tumor-related emergencies requiring urgent treatment, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression. 3. Significant cardiovascular diseases, including: * Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmia, or having undergone angioplasty, stent implantation, or coronary artery bypass surgery. * Clinically significant QT/QTcF prolongation (QT/QTcF \> 470 ms in females or \> 450 ms in males). 4. Clinically significant bleeding tendency or coagulation disorders, such as hemophilia. 5. HIV or syphilis infection; active hepatitis B or C: * Hepatitis B: HBV-DNA ≥ 1000 IU/mL. * Hepatitis C: Positive HCV RNA with abnormal liver function. 6. History of involuntary commitment due to psychiatric disorders or other psychological conditions deemed unsuitable for treatment by the investigator. 7. Presence of other autoimmune diseases, or long-term use of immunosuppressive agents or corticosteroids. 8. Poor medication compliance. 9. Any other condition that the investigator considers grounds for exclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Incidence and severity of adverse events | First 3 month post CAR-T cells and CAR-DCs infusion | To evaluate adverse events occurring within the first three months following infusion of EphA2-targeted CAR- T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies. |
| Efficacy: Remission Rate | 3 months post CAR-T cells and CAR-DCs infusion | To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Rate | Up to 24 months post CAR-T cells and CAR-DCs infusion | — |
| Duration of Response | Up to 24 months post CAR-T cells and CAR-DCs infusion | — |
| Progression-Free Survival | Up to 24 months post CAR-T cells and CAR-DCs infusion | — |
| Objective Response Rate in Participants Receiving Different Doses of CAR-DCs | Up to 24 months post CAR-T cells and CAR-DCs infusion | The proportion of participants in each CAR-DCs dose cohort (5x10\^6, 1x10\^7, 3x10\^7, and 9x10\^7 cells) who achieve an objective tumor response, including completeremission (CR) or partial remission (PR). All participants received a fixed dose of EphA2-targeted CAR-T cells (2x10\^6 cells/kg) following CAR-DCs infusion. |
| Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs | Up to 24 months post CAR-T cells and CAR-DCs infusion | To evaluate adverse events occurring following infusion of EphA2-targeted CAR-DCs and CAR-T cells. Participants will receive CAR-DCs at one of four dose levels (5x10\^6, 1x1 0\^7, 3x10\^7, and 9x10\^7 cells), followed by a fixed dose of EphA2-targeted CAR-T cells(2x10\^6 cells/kg). The assessment includes the incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies. |
| In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring | First 2 weeks post CAR-T cells and CAR-DCs infusion | The copy number of CAR-T cells and CAR-DCs in PBMCs will be measured by qPCR to assess in vivo persistence. Serum cytokine levels, including IL-2, IL-4, IL-6, IFN-γ, TNF-α, IL-10, IL-12, and IL-17A, will be quantified by ELISA to evaluate immune activation following cell infusion. |
| Overall Survival | Up to 24 months post CAR-T cells and CAR-DCs infusion | — |
Countries
China
Contacts
Primary ContactYing Yuan
Backup ContactShanshan Weng
Outcome results
None listed