Autologous CAR T-Cells Targeting the GD2 Antigen for Lung Cancer

Официальное название

Administration of T Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch in Subjects With Lung Cancer

Обзор

This is a phase 1, single-center, open-label study that enrolls adult subjects with extensive stage lung cancer or stage IV non-small cell lung cancer that is platinum-refractory and received PD-1 and/or PD-L1 therapy. The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen (iC9-GD2.CAR.IL-15 T cells) in subjects with lung cancer. How much (dose) of the iC9-GD2.CAR.IL-15 T cells are safe to use without causing too many side effects and what is the maximum dose that could be tolerated will be studied. Modified immune cells as an experimental treatment that combines antibodies and T cells will be used. Antibodies are proteins that protect the body from foreign invaders like bacteria. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill viruses and other cells, including tumor cells. Although antibodies and T cells have been used to treat cancer and they both have shown promise, neither alone has been able to cure most patients. This study will combine T cells and antibodies to create a more effective treatment. The treatment that is being researched in this study is called autologous T lymphocyte chimeric antigen receptor cells targeted against the disialoganglioside (GD2) antigen that expresses Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9). The short name for this treatment is iC9.GD2.CAR.IL-15 T cells therapy is an experimental therapy and has not been approved by the Food and Drug Administration. There are two steps. In the first step, blood will be collected from the subjects to prepare the iC9-GD2.CAR.IL-15 T cells. T cells will be isolated from the blood and modified to make iC9-GD2.CAR.IL-15. In the second step, the iC9-GD2.CAR.IL-15 T cells produced from the subject's own blood will be administered to the subject.

Вмешательства

• Биопрепарат iC9.GD2.CAR.IL-15 T Infusion
  iC9-GD2.CAR.IL-15 T-cells product will be administered via intravenous injection over 5 - 10 minutes.

Первичные конечные точки

• Number of participants with adverse event [Срок оценки: Up to 4 weeks]
• Cytokine Release Syndrome (CRS) [Срок оценки: Up to 4 weeks]
• Neurotoxicity [Срок оценки: Up to 4 weeks]

Вторичные конечные точки (8)

• Identification of Recommended phase 2 dose (RP2D) [Срок оценки: Up to 4 weeks]
• Overall Response Rate (ORR) [Срок оценки: Up to 4 weeks]
• Progression Free Survival (PFS) [Срок оценки: Up to 2 years]
• Overall Survival (OS) [Срок оценки: Up to 2 years]
• Duration of Response (DOR) [Срок оценки: Up to 2 years]
• Duration of Benefit [Срок оценки: Up to 2 years]
• Disialoganglioside (GD2) Expression [Срок оценки: Baseline]
• Disialoganglioside Expression and tumor response rate correlations [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Written informed consent to undergo cell procurement explained to, understood by, and signed by the subject.
• Subject has a life expectancy of ≥ 12 weeks.
• Subject must be platinum-refractory and either currently receiving or has previously received a PD1/PDL1 inhibitor
• Use of systemic corticosteroids at doses ≥10 mg prednisone daily or it's equivalent; those receiving <10 mg daily may be enrolled at the discretion of the investigator.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement.
• Subject has demonstrated adequate organ function.

Критерии исключения

1 . Subject has less than 12 weeks of life expectancy.

2\. Subject did not receive platinum-based chemotherapy

3\. Subject does not have adequate organ function.

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

США · 1 центр

• Lineberger Comprehensive Cancer Center — Chapel Hill

Публикации

• Ouyang W, Xu Z, Guan S, Hu Y, Gou X, Liu Z, Guo W, Huang Y, Zhang L, Zhang X, Li T, Yang B. Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer. Int J Biol Sci. 2025 Jan 20;21(3):1322-1341. doi: 10.7150/ijbs.105973. eCollection 2025. PMID 39897044

Идентификаторы

NCT: NCT05620342 · LCCC2115-ATL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗