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

Official title

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

Overview

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

• Other Multi-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.
• Other MRI
  MRI will be conducted to investigate image characteristics during treatment

Primary outcome measures

• Baseline proportion and location of different immune cell subsets associated with efficacy [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 [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 [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 [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 [Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

Secondary outcome measures (6)

• Early changes (within 8 weeks) of proportion and location of different immune cell subsets after treatment associated with efficacy [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 [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 [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 [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 [Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]
• MR image characteristics [Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Jian Li — Beijing

Identifiers

NCT: NCT06549907 · CGOG-EXPLORE-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗