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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат EphA2-targeted CAR-T Cells
  Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2
• Биопрепарат EphA2-targeted CAR-DCs
  Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting EphA2

Первичные конечные точки

• Safety: Incidence and severity of adverse events [Срок оценки: First 3 month post CAR-T cells and CAR-DCs infusion]
• Efficacy: Remission Rate [Срок оценки: 3 months post CAR-T cells and CAR-DCs infusion]

Вторичные конечные точки (7)

• Progression-Free Survival [Срок оценки: Up to 24 months post CAR-T cells and CAR-DCs infusion]
• Overall Survival [Срок оценки: Up to 24 months post CAR-T cells and CAR-DCs infusion]
• Relapse Rate [Срок оценки: Up to 24 months post CAR-T cells and CAR-DCs infusion]
• Duration of Response [Срок оценки: 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 [Срок оценки: First 2 weeks post CAR-T cells and CAR-DCs infusion]
• Objective Response Rate in Participants Receiving Different Doses of CAR-DCs [Срок оценки: Up to 24 months post CAR-T cells and CAR-DCs infusion]
• Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs [Срок оценки: Up to 24 months post CAR-T cells and CAR-DCs infusion]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Any other condition that the investigator considers grounds for exclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT06972576 · 2022-0164

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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