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

NCT06972576 | Recruiting Phase 1

• 1 other identifier: 2022-0164
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Chimeric Antigen Receptor Dendritic Cells; Chimeric Antigen Receptor T-Cells; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety: Incidence and severity of adverse events

  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.

  First 3 month post CAR-T cells and CAR-DCs infusion

• Efficacy: Remission Rate

  To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)

  3 months post CAR-T cells and CAR-DCs infusion

Secondary Outcomes (7)

• Progression-Free Survival

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• Overall Survival

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• 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

• 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

Study Arms (1)

CAR-T and CAR-DC Combination Therapy

EXPERIMENTAL

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

Biological: EphA2-targeted CAR-T Cells; Biological: EphA2-targeted CAR-DCs

Interventions

EphA2-targeted CAR-T Cells BIOLOGICAL

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

CAR-T and CAR-DC Combination Therapy

EphA2-targeted CAR-DCs BIOLOGICAL

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

CAR-T and CAR-DC Combination Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Tumor tissue tested positive for EphA2 expression by immunohistochemistry (≥20%).
• 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).
• ECOG performance status: 0-1.
• Expected survival ≥6 months.
• 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.
• 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.
• Subjects of reproductive potential must be willing to use effective contraception.
• Ability to understand and voluntarily sign the informed consent form.
• Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Pathologically confirmed mixed histology, such as adenosquamous carcinoma of the lung.
• Tumor-related emergencies requiring urgent treatment, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
• 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).
• Clinically significant bleeding tendency or coagulation disorders, such as hemophilia.
• 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.
• History of involuntary commitment due to psychiatric disorders or other psychological conditions deemed unsuitable for treatment by the investigator.
• Presence of other autoimmune diseases, or long-term use of immunosuppressive agents or corticosteroids.
• Poor medication compliance.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ying Yuan

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Yuan

CONTACT

+86-13858193601; yuanying1999@zju.edu.cn

Shanshan Weng

CONTACT

+86-13758118823; 2310053@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: May 9, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 15, 2025

Record last verified: 2025-04

Locations

CN (1)