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.
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.
Study Type
OBSERVATIONAL
Enrollment
50
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.
MRI will be conducted to investigate image characteristics during treatment
Jian Li
Beijing, Beijing Municipality, China
RECRUITINGBaseline proportion and location of different immune cell subsets associated with efficacy
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.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline tumor gene alterations associated with efficacy
Baseline tumor gene alterations will be assessed by whole exome sequencing using pre-treatment tissue or blood samples
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline clinical characteristics associated with efficacy
Baseline clinical characteristics include age of onset, gender, family history, pathological type of tumor, primary tumor site, metastatic site, tumor size, and previous treatment.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline tumor-associated proteins associated with efficacy
Tumor-associated proteins will be assessed by microproteomics using pre-treatment blood or urine samples.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline intestinal flora associated with efficacy
Intestinal flora will be assessed by macro transcriptome sequencing using pre-treatment stool samples.
Time frame: 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 proportion and location of different immune cell subsets after treatment associated with efficacy
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-and post-treatment samples.
Time frame: 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 tumor gene alterations will be assessed by whole exome sequencing using pre-and post-treatment tissue or blood samples.
Time frame: 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
Tumor-associated proteins will be assessed by microproteomics using pre-and post treatment blood or urine samples.
Time frame: 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
Intestinal flora will be assessed by macro transcriptome sequencing using pre- and post-treatment stool samples.
Time frame: 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
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-and post-treatment samples.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Ting Xu
CONTACT
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MR image characteristics
MR image characteristics at baseline and their changes when tumor responded or progressed
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose