Tumor Immunotherapy and Microbiome Analysis

Study Overview
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Brief Summary
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The composition of the gut microbiome has been associated with response and the development of toxicities on immune checkpoint inhibitors (ICIs) in multiple tumor types. The aim of this study is to examine the gut microbiome composition in patients undergoing standard of care treatment for advanced/unresectable and/or metastatic solid tumors with ICIs. Fecal samples and peripheral blood samples will be collected to further characterize the diversity of gut bacteria and to study potential mechanisms by which gut bacteria impact the immune response.

Detailed Description
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This is a prospective study of gut microbial markers. Patients with histologically confirmed advanced/unresectable or metastatic solid tumors who are planned to initiate standard of care ICIs or are undergoing standard of care treatment with ICIs will be approached for participation in the study.

Official Title
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Tumor Immunotherapy and Microbiome Analysis

Conditions
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Advanced Solid Tumor

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign written and voluntary informed consent Adult patients aged >=18, male or female Eastern Cooperative Group (ECOG) performance status 0-2 Histologic diagnosis of an advanced/unresectable or metastatic solid tumor Measurable disease as per RECIST 1.1 criteria Be suitable for or receiving ICI treatment Prior immunotherapy allowed Be willing and able to provide fecal and blood specimens for analysis as per protocol Exclusion Criteria: Subjects with a history of inflammatory bowel disease, chronic diarrhea or malabsorption syndromes and significant prior bowel resection as judged by the study investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects with advanced solid tumors starting immunotherapy<br>Subjects with advanced solid tumors planned to initiate standard of care immune checkpoint inhibitors | |
| Subjects with advanced solid tumors receiving ICIs<br>Subjects with advanced solid tumors already receiving standard of care immune checkpoint inhibitors | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative abundance and composition of immunotherapy response-associated bacterial species in patients with advanced/unresectable or metastatic solid tumors | Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing | 6 months | 
| Relative abundance and composition of immunotherapy toxicity-associated bacterial species in patients with advanced/unresectable or metastatic solid tumors | Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing; IgA sequencing of fecal samples from patients who develop diarrhea/colitis | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the composition of the intestinal microbiome induced by ICIs | Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing | 6 months | 
| Relative abundance of bacterial DNA in peripheral blood samples | Blood microbial abundance measured via qPCR | 6 months | 
| Changes in immune cell subsets in the systemic circulation upon progression on ICIs correlated with changes in microbiome composition | Flow cytometry of blood at baseline and at development of progressive disease and analysis of microbiome composition at baseline and at development of progressive disease | 2 years | 
| Identification of serum metabolites in systemic circulation and correlation with intestinal microbiome composition | Analysis of serum metabolites using chromatography coupled to tandem mass spectrometry | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Checkpoint Inhibitor, Microbiome, Immune-Mediated Toxicity