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

NCT ID: NCT06972576

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-09
• Study Completion Date: 2027-04-30

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-T and CAR-DC Combination Therapy

This arm involves the sequential administration of two biological interventions with EphA2-targeted CAR-DCs administered first, followed by EphA2-targeted CAR-T cells.

Group Type: EXPERIMENTAL

EphA2-targeted CAR-T Cells

Intervention Type: BIOLOGICAL

Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2

EphA2-targeted CAR-DCs

Intervention Type: BIOLOGICAL

Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2

Interventions

EphA2-targeted CAR-T Cells

Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2

Intervention Type: BIOLOGICAL

EphA2-targeted CAR-DCs

Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ying Yuan

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Locations

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ying Yuan

Role: CONTACT

yuanying1999@zju.edu.cn

+86-13858193601

Shanshan Weng

Role: CONTACT

2310053@zju.edu.cn

+86-13758118823

Facility Contacts

Ying Yuan

Role: primary

yuanying1999@zju.edu.cn

+86-13858193601

Other Identifiers

2022-0164

Identifier Type: -

Identifier Source: org_study_id