A Biomarker Exploratory Study of Efficacy and Prognosis of Dual Blockade of PD1/PDL1 and CTLA4 in Combination of Anti-angiogenic Treatment in MSS Metastatic Colorectal Cancers and MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Baseline intestinal flora associated with efficacy
研究概览
简要总结
This study is a single-center prospective exploratory research, aiming to identify clinical characteristics and biomarkers associated with the therapeutic effects of dual PD1/PDL1 and CTLA4 blockade plus anti-angiogenic therapy and investigate MR image characteristics during treatment in patients with MSS metastatic colorectal cancer and MSI solid tumors resistant to PD-1/PD-L1 antibody monotherapy.
详细描述
This study is a single-center prospective exploratory research. Patients with MSS metastatic colorectal cancer and MSI solid tumors resistant to PD-1/PD-L1 antibody monotherapy who are treated with dual PD1/PDL1 and CTLA4 blockade combined with anti-angiogenic therapy in the Department of Gastrointestinal Oncology of Peking University Cancer Hospital will be enrolled. Their clinical-pathological features and specimens will be collected at baseline, at each tumor assessment point, and at disease progression.
This study aims to identify clinical characteristics and biomarkers associated with the therapeutic effects through multi-omics approaches, and to investigate MR image characteristics during treatment. Samples include tissue, blood, urine and stool, and multi-omics approaches include single-cell sequencing, spatial transcriptome sequencing, macro transcriptome sequencing, whole exome sequencing, microproteomics, immunohistochemistry, and multiplex fluorescence immunohistochemistry.
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
- •Pathologically confirmed MSS metastatic colorectal cancers or MSI solid tumors refractory to PD1/PDL1 antibody monotherapy
- •Receiving dual blockade of PD1/PDL1 and CTLA4 in combination of anti-angiogenic treatment with or without other therapies
排除标准
- •●Having malignancies in non-gastrointestinal system that have not been cured (Lynch syndrome not included)
结局指标
主要结局
Baseline intestinal flora associated with efficacy
时间窗: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Intestinal flora will be assessed by macro transcriptome sequencing using pre-treatment stool samples.
Baseline tumor gene alterations associated with efficacy
时间窗: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline tumor gene alterations will be assessed by whole exome sequencing using pre-treatment tissue or blood samples
Baseline proportion and location of different immune cell subsets associated with efficacy
时间窗: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Proportion and location of different immune cell subsets will be assessed by single-cell sequencing, spatial transcriptome sequencing, immunohistochemistry, and multiplex fluorescence immunohistochemistry using pre-treatment samples.
Baseline clinical characteristics associated with efficacy
时间窗: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline clinical characteristics include age of onset, gender, family history, pathological type of tumor, primary tumor site, metastatic site, tumor size, and previous treatment.
Baseline tumor-associated proteins associated with efficacy
时间窗: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Tumor-associated proteins will be assessed by microproteomics using pre-treatment blood or urine samples.
次要结局
- Early changes (within 8 weeks) of proportion and location of different immune cell subsets after treatment associated with efficacy(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Early changes (within 8 weeks) of tumor-associated proteins after treatment associated with efficacy(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Early changes (within 8 weeks) of tumor gene alterations after treatment(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Early changes (within 8 weeks) of intestinal flora after treatment associated with efficacy(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Longitudinal on-treatment changes of proportion and location of different immune cell subsets at baseline, tumor shrinkage and progression(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- MR image characteristics(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)