Administration of T Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch in Subjects With Lung Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of participants with adverse event
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
iC9.GD2.CAR.IL-15 T Therapy
Experimental: Single Arm 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 will receive iC9.GD2.CAR.IL-15 T cells were manufactured from their collected blood sample.
干预措施: iC9.GD2.CAR.IL-15 T Infusion (Biological)
结局指标
主要结局
Number of participants with adverse event
时间窗: Up to 4 weeks
The number of participants with adverse events (AE)s will be reported as a measure of the safety and tolerability of C9.GD2.CAR.IL-15 T. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Cytokine Release Syndrome (CRS)
时间窗: Up to 4 weeks
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38\^ o C , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.
Neurotoxicity
时间窗: Up to 4 weeks
Neurotoxicity will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Immune effector cell-associated neurotoxicity syndrome (ICANS) Consensus Grading criteria. ICANS grading criteria are outlined in the protocol on a scale from 1 (mild) to 4 (critical) based on the Immune Effector Cell-Associated Encephalopathy (ICE) Score. Grade 1:Score: 7-9 (mild impairment), Grade 2:Score: 3-6 (moderate impairment), Grade 3: Score: 0-2 (severe impairment), Grade 4: Score: Subject in critical condition, and/or obtunded and cannot perform an assessment of tasks.
次要结局
- Progression Free Survival (PFS)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Duration of Benefit(Up to 2 years)
- Disialoganglioside Expression and tumor response rate correlations(Up to 2 years)
- Identification of Recommended phase 2 dose (RP2D)(Up to 4 weeks)
- Overall Response Rate (ORR)(Up to 4 weeks)
- Duration of Response (DOR)(Up to 2 years)
- Disialoganglioside (GD2) Expression(Baseline)