Malignant Melanoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Triple-Negative Breast Cancer
Conditions
Brief summary
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.
Interventions
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
Sponsors
VastBiome
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women ≥18 years of age 2. 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 3. Diagnosed with stages I-IV primary NSCLC, MM, TNBC or RCC 4. 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 5. Able to provide informed consent and answer study questionnaires in either English or Spanish 6. Able to provide stool specimens for research purposes
Exclusion criteria
1. Mental incapacity 2. Incarcerated individuals 3. Pregnancy (by self-report of pregnancy status) 4. Experiencing active brain metastasis/metastases 5. Treatment with checkpoint inhibitor in off-label capacity or through a clinical/interventional trial 6. Active participation in an immuno-oncology clinical/interventional trial or pharma-sponsored observational study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) ] | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome samples correlation | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) | 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). |
| Microbiome correlation to blood biomarkers | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) | 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. |
| Blood samples correlation | Time Frame: prior to initiation of checkpoint therapy (i.e. Baseline) and at the end of Cycle 2 (at approximately 6-8 weeks) | 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). |
Countries
United States
Contacts
Primary ContactHanane Arib, MS
Backup ContactPeter McCaffrey, MD
Outcome results
None listed