A Biomarker Exploratory Study of Dual Blockade of PD1/PDL1 and CTLA4 and Anti-angiogenic Therapy

Recruiting

• Conditions: MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy; MSS Metastatic Colorectal Cancers
• Interventions: Other: Multi-omics testing; Other: MRI

• Registration Number: NCT06549907
• Lead Sponsor: Peking University Cancer Hospital & Institute

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.

Study Timeline

• Study First Submitted: 2023-11-10
• Study Start: 2024-01-10
• Status Verified: 2024-08
• Study First Submitted QC: 2024-08-08
• Last Update Submitted: 2024-08-08
• Study First Posted: 2024-08-12
• Last Update Posted: 2024-08-12
• Primary Completion: 2028-09-30
• Study Completion: 2028-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Exploratory group	Multi-omics testing	Patients treated with dual blockade of PD1/PDL1 and CTLA4 in combination of anti-angiogenic treatment
Exploratory group	MRI	Patients treated with dual blockade of PD1/PDL1 and CTLA4 in combination of anti-angiogenic treatment

Primary Outcome Measures

Name	Time	Method
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.
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 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 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.

Secondary Outcome Measures

Name	Time	Method
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.
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 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 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.
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

Trial Locations

Locations (1)

Jian Li; 🇨🇳 Beijing, Beijing, China