Clinical trial NCT06549907: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: MSS Metastatic Colorectal Cancers
MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2024-08-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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 plus anti-angiogenic therapy

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.

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)

Primary outcomes:
measure: Baseline proportion and location of different immune cell subsets associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Baseline tumor gene alterations associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Baseline clinical characteristics associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Baseline tumor-associated proteins associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Baseline intestinal flora associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Secondary outcomes:
measure: Early changes (within 8 weeks) of proportion and location of different immune cell subsets after treatment associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Early changes (within 8 weeks) of tumor gene alterations after treatment
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Early changes (within 8 weeks) of tumor-associated proteins after treatment associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Early changes (within 8 weeks) of intestinal flora after treatment associated with efficacy
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Longitudinal on-treatment changes of proportion and location of different immune cell subsets at baseline, tumor shrinkage and progression
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: MR image characteristics
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Jian Li
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jian Li
role: STUDY_DIRECTOR
References: