A Biomarker Exploratory Study of Dual Blockade of PD1/PDL1 and CTLA4 and Anti-angiogenic Therapy
NCT Number: NCT06549907
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: MSS Metastatic Colorectal Cancers|MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy
Interventions: OTHER: Multi-omics testing|OTHER: MRI
Sponsor: Peking University Cancer Hospital & Institute
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 50
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-01-10
Completion Date: 2028-09-30
Locations: Jian Li, Beijing, Beijing, 100142, China

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.

Primary Outcome Measures: Baseline 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., 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, 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., 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., 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., Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Secondary Outcome Measures: 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., 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., 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., 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., 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., Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose|MR image characteristics, MR image characteristics at baseline and their changes when tumor responded or progressed, Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose