MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy, MSS Metastatic Colorectal Cancers
Conditions
Brief summary
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.
Detailed description
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.
Interventions
OTHERMulti-omics testing
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.
OTHERMRI
MRI will be conducted to investigate image characteristics during treatment
Sponsors
Peking University Cancer Hospital & Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
●Having malignancies in non-gastrointestinal system that have not been cured (Lynch syndrome not included)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline proportion and location of different immune cell subsets associated with efficacy | 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 tumor gene alterations associated with efficacy | 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 clinical characteristics associated with efficacy | 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 | 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. |
| Baseline intestinal flora associated with efficacy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| MR image characteristics | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | MR image characteristics at baseline and their changes when tumor responded or progressed |
| 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 | Baseline tumor gene alterations will be assessed by whole exome sequencing using pre-and post-treatment tissue or blood samples. |
| 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 | Tumor-associated proteins will be assessed by microproteomics using pre-and post treatment blood or urine samples. |
| 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 | Intestinal flora will be assessed by macro transcriptome sequencing using pre- and post-treatment stool samples. |
| 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 | 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. |
Countries
China
Contacts
Primary ContactZhenghang Wang
Backup ContactTing Xu
Outcome results
None listed