Clinical Study on the Efficacy and Safety of CAR-DC in the Treatment of Advanced Solid Tumors

Обзор

This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC), glypican-3 (GPC3) and carcinoembryonic antigen (CEA).

Подробное описание

Dendritic cell (DC) plays a vital role in T cell priming and anti-tumor immune activation. A novel kind of engineered DC, chimeric antigen receptor-dendritic cell (CAR-DC) can reverse the immune suppression in tumor-microenvironment (TME) to enhance anti-tumor therapy. This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of CAR-DC in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC) , glypican-3 (GPC3) AND carcinoembryonic antigen (CEA). A total number of 10 patients will receive two rounds of intravenous infusions of 30 million CAR-DC at an interval of 14 days and receive follow-up visits after the second round of infusion up to 1 or 2 years.

Вмешательства

• Биопрепарат CAR-DC treatment
  The patients will receive intravenous injection (iv) of 30 million CAR-DC for two rounds at an interval of 14 days.

Первичные конечные точки

• To evaluate the objective response rate (ORR) of CAR-DC therapy [Срок оценки: 2 years]
• To evaluate the disease control rate (DCR) of CAR-DC therapy [Срок оценки: 2 years]
• The quality of life assessment of CAR-DC therapy [Срок оценки: 2 years]

Вторичные конечные точки (3)

• To evaluate the cytokine release syndrome (CRS) of CAR-DC therapy [Срок оценки: 2 years]
• To evaluate the neurotoxicity of CAR-DC therapy [Срок оценки: 2 years]
• To evaluate the survival time of CAR-DC in patient peripheral blood [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Aged 18-70, regardless of gender;
• Diagnosed as EphA2or Claudin18.2, TROP2, HER2, GCC, GPC-3, CEA positive advanced solid tumors, such as lung cancer, liver cancer, colorectal cancer, gastric cancer, etc; Note: Advanced solid tumors refer to locally advanced (stage III patients) and metastatic advanced (stage IV patients) TNM staging by the American Cancer Society (AJCC).
• Immunohistochemical analysis of pathological tissue approves positive expression for one of the following antigens, including EphA2, Claudin18.2, TROP2, HER2, GCC, GPC-3 and CEA, with expression intensity ≥ 2+;
• Failed response to standard treatment or unwilling/intolerant to all standard treatment regimens;
• Imaging indicates measurable tumor lesions;
• ECOG PS score: 0-2;
• Expected survival time is greater than 3 months;
• Maintaining good organ function and bone marrow reserve capacity:

• Bone marrow: Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L, platelet count ≥ 50 × 10\^9/L, hemoglobin ≥ 80 g/L, and no blood transfusion or biological regulator treatments (such as granulocyte colony-stimulating factor, red blood cell growth factor, etc.) within 14 days prior to screening;
• Kidney: creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate (Ccr) ≥ 50 mL/min (according to the Cockcroft-Gault formula); Urine output>10 mL/h within 16-24 hours;
• Coagulation: International Normalized Ratio (INR) ≤ 1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (excluding those receiving therapeutic anticoagulants);
• Other: Blood oxygen saturation ≥ 90%, negative fecal occult blood test, etc.
• The patient is willing to enroll and signs a written informed consent form, and is able to undergo diagnosis, treatment, and visits according to the protocol.

Критерии исключения

• Pregnant and lactating women; (The pregnancy test results are included in the CRF)
• The patient can not guarantee effective contraceptive measures (such as condoms or birth control pills) within one year after enrollment;
• Patients with brain metastases exhibiting significant psychiatric and neurological symptoms;
• Serious heart diseases such as arrhythmia;
• Autoimmune diseases;
• Active bacterial, fungal, and other infections;
• Infectious diseases: such as HIV, syphilis, tuberculosis, viral hepatitis and other diseases;
• Patients are receiving medications such as glucocorticoids, thrombolytic drugs, and antipsychotic drugs;
• Patients are believed not suitable for this clinical trial for other reasons by investigators.

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

• Peking University Shenzhen Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT07504445 · 2024-164 (Research) -02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗