The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Study Overview
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Brief Summary
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The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types.

Official Title
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The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Conditions
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Non-Small-Cell Lung Carcinoma, Malignant Melanoma, Renal Cell Carcinoma, Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: Checkpoint Inhibitor, Immune


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥18 years of age Screened negative for COVID-19 symptoms at time of consent, as per institutional policy and as applicable for the duration of the COVID-19 pandemic Diagnosed with stages I-IV primary NSCLC, MM, TNBC or RCC Plan to be treated at a partner cancer site with a checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti-CTLA-4) as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent Able to provide informed consent and answer study questionnaires in either English or Spanish Able to provide stool specimens for research purposes Exclusion Criteria: Mental incapacity Incarcerated individuals Pregnancy (by self-report of pregnancy status) Experiencing active brain metastasis/metastases Treatment with checkpoint inhibitor in off-label capacity or through a clinical/interventional trial Active participation in an immuno-oncology clinical/interventional trial or pharma-sponsored observational study

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

| Intervention/Treatment |
| --- |
|Drug: Checkpoint Inhibitor, Immune|anti-PD-1, anti-PD-L1, or anti-CTLA-4 as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in microbiome composition from baseline to after Cycle 2 of checkpoint therapy (6-8 weeks) by analyzing longitudinally-collected stool specimens of 800 patients with primary NSCLC, MM, RCC, and TNBC | Microbiome evaluation with whole metagenome shotgun sequencing to assess changes in the relative abundance of microbial taxa (measured as percentage abundance per microbial species and changes in percentage abundance between baseline and cycle 2 timepoints) in patients who are receiving checkpoint blockade immunotherapy as the standard of care | prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 of checkpoint blockade immunotherapy (at approximately 6-8 weeks) ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome samples correlation | Definition of a correlation between the gut microbiome and circulating cytokines (specifically IL-2, IL-10, TNF-alpha, IFN-gamma, and G-CSF) and therapeutic response (defined using RECIST criteria). | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) | 
| Microbiome correlation to blood biomarkers | Definition of a correlation between the gut microbiome (measured as percent abundance of microbial taxa derived from whole-metagenome shotgun sequencing) and plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) in patients receiving checkpoint blockade immunotherapy. | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) | 
| Blood samples correlation | Definition of a correlation between plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) and therapeutic response (defined using RECIST criteria). | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) |