Combined CAR-DC and CAR-T Cell Therapy for Non-small Cell Lung Cancer

Clinical Study of Combined EphA2-targeted CAR-DC and CAR-T Cell Therapy for Non-small Cell Lung Cancer

This study is testing a new combination therapy using special immune cells to see if it can help people with advanced non-small cell lung cancer feel better and live longer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: chemotherapy, immunotherapy, CAR-T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06972576 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and preliminary efficacy of a combination therapy using EphA2-targeted CAR-DCs and CAR-T cells in patients with advanced non-small cell lung cancer. It is an open-label, single-arm trial focusing on determining the maximum tolerated dose of the CAR-DCs while assessing overall response rates and survival outcomes. The study also aims to analyze the persistence and functional activity of the infused CAR-T cells and CAR-DCs in the patients.

Who should consider this trial

Good fit: Ideal candidates include patients with stage IV non-small cell lung cancer who have measurable lesions and have previously failed standard treatments.

Not a fit: Patients with early-stage non-small cell lung cancer or those who have not received prior systemic therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced non-small cell lung cancer who have limited alternatives.

How similar studies have performed: While CAR-T cell therapies have shown promise in hematological malignancies, this specific combination approach for non-small cell lung cancer is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Principal investigator: Ying Yuan — Second Affiliated Hospital, School of Medicine, Zhejiang University
• Study coordinator: Ying Yuan

Conditions: Non-Small Cell Lung Cancer, Chimeric Antigen Receptor Dendritic Cells, Chimeric Antigen Receptor T-Cells