Maximizing Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Mechanisms of resistance to anti-PD-1 blockade
研究概览
简要总结
This study explores the role of T cells in monitoring disease status and response during anti-PD-1/PD-L1 treatment in patients with melanoma, lung and other cancer types. Measuring levels of specific targets such as Bim and soluble PD-L1 during therapy may help track treatment resistance and clinical outcomes. This information may also help researchers determine why some people with melanoma, lung and other cancer types respond to PD-1/PD-L1 treatment and others do not.
详细描述
PRIMARY OBJECTIVES:
I. Establish the role of Bim for monitoring disease status during anti-PD-1 therapy.
II. Identify the mechanisms of resistance to anti-PD-1 blockade. III. Quantify and modulate levels of NKG7 messenger ribonucleic acid (mRNA) in CD8+ T cells.
OUTLINE: This is an observational study.
Patients undergo blood sample collection throughout the study. Patients also undergo optional stool sample collection and have their medical records reviewed on study. In addition, patients provide previously-collected tissue sample, if available.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Are 18 years of age or older
- •Have histologic evidence of locally or regionally advanced or stage IV malignancy
- •Are considered appropriate for starting therapy with anti-PD-1/anti-PD-L1 monoclonal antibody by their treating physician (prior therapy with immune checkpoint inhibitor (ICI) is allowed)
- •Have an understanding of the protocol and its requirements, risks, and discomforts
- •Are willing to undergo peripheral blood collection at the time points mentioned in the protocol
- •Are able and willing to sign an informed consent
排除标准
- •Inability on the part of the patient to understand the informed consent or be compliant with the protocol
- •Patients receiving any concurrent anti-cancer therapy or investigational agents (with the exception of an anti-PD-1/anti-PD-L1 agent as mentioned above)
- •Patients who are pregnant, nursing, or are of childbearing potential and are unwilling to employ adequate contraception
结局指标
主要结局
Mechanisms of resistance to anti-PD-1 blockade
时间窗: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Will be assessed by reviewing blood samples to determine whether high sPD-L1 levels are associated with higher Bim levels in CD11ahigh PD-1+CD8+ T cells and decreased response to single-agent anti-PD1 blocking antibody in patients with cancer.
Quantify and modulate levels of NKG7 mRNA in CD8+ T cells
时间窗: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
CD8+ T cells will be isolated from the peripheral blood of patients with advanced cancer, and messenger ribonucleic acid (mRNA) will be isolated. Qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR) assays will be performed on these samples in order to determine the levels of six different mRNA splice variants of NKG7. Results will be compared to clinical outcome.
Role of Bim for monitoring disease status during anti-PD-1 therapy
时间窗: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Will be assessed by serial measurements of Bim levels in tumor-reactive CD8+ T cells from the peripheral blood of patients with advanced cancer undergoing therapy with an anti-PD-1 monoclonal antibody and correlate them with clinical outcome.
次要结局
未报告次要终点