CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

Официальное название

Phase I Trial to Evaluate Safety and Preliminary Efficacy of CLDN6/GPC3/Mesothelin/AXL-CAR-NK in Patients With CLDN6/GPC3/Mesothelin/AXL-positive Advanced Solid Tumors

Обзор

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

Подробное описание

1. Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study; 2. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed; 3. To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD); 4. Evaluate the clinical results as needed. 5. Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

Вмешательства

• Биопрепарат Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells
  Engineering Claudin6, GPC3, Mesothelin, or AXL targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, GPC3, Mesothelin, or AXL, and then transfusing them back the patients. In some cases, the CAR-NK cells will be combined with CBD or NAD to enhance the therapeutic efficacy.

Первичные конечные точки

• Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 [Срок оценки: After CAR-NK cells infusion, up to 52 weeks.]

Вторичные конечные точки (3)

• Objective Response Rate (ORR) [Срок оценки: After CAR-NK cells infusion, up to 52 weeks.]
• Disease control rate (DCR) [Срок оценки: up to 52 weeks.]
• Duration of response (DOR) [Срок оценки: up to 36 months]

Критерии участия

Критерии включения

• patients with advanced ovarian cancer or other cancers with expression of claudin6.
• Life expectancy >12 weeks
• Adequate heart,lung,liver,kidney function
• Available autologous transduced NK cells with greater than or equal to 20% expression of Claudin6, GPC3, Mesothelin, or AXL-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Критерии исключения

• Had accepted gene therapy before;
• Tumor size more than 25cm;
• Severe virus infection such as HBV,HCV,HIV,et al
• Known HIV positivity
• History of liver/renal transplantation
• Active infectious disease related to bacteria, virus,fungi,et al
• Other severe diseases that the investigators consider not appropriate;
• Pregnant or lactating women
• Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
• Other conditions that the investigators consider not appropriate. -

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Second Affiliated Hospital of Guangzhou Medical University — Гуанчжоу

Публикации

• Li J, Hu H, Lian H, Yang S, Liu M, He J, Cao B, Chen D, Hu Y, Zhi C, Shen Y, Ye X, He B, Zhao M, Fan W, Xu L, Leidner R, Wu Q, Yang L, Zhang Z. NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer. Int J Biol Sci. 2024 Feb 11;20(5):1578-1601. doi: 10.7150/ijbs.88539. eCollection 2024. PMID 38481806

Идентификаторы

NCT: NCT05410717 · ZZCARNK-017

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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