Gut and Tumor Microbiome in Patients With Advanced ER-positive and HER2-negative Breast Cancer or Advanced Melanoma Undergoing PD-1 Checkpoint Inhibitor Therapy.

Study Overview
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Brief Summary
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The purpose of this research study is to collect samples of blood and stool and analyse primary tumor from participants with breast cancer or melanoma to see how the bacteria in the body affect cancer and how well it responds to treatment. By comparing samples and data from multiple participants with breast cancer or melanoma, it may be possible to identify how a person's gut health and tumor microenvironment affects how they respond to certain cancer treatments.

Detailed Description
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After being informed about the study and potential risks, all participants giving written informed consent will provide a pre-treatment stool sample looking at the gut microbiome, primary tumor sequencing analysis to infer tumor microbiome, and a blood sample for the CyTOF whole blood Immune Profile. Blood tests (full blood count, renal profile, liver profile, C-reactive protein), medical history, concomitant medications, and the Eastern Cooperative Oncology Group (ECOG) performance level will be obtained through a mixture of self-reported and data collated from the electronic health record (EHR). Two food frequency questionnaires will be given to participants to complete at two timepoints: at screening and at end of study. There are 5 study visits. Participants will provide a stool sample for gut microbiome sequencing at weeks 2 and 4 of the study. During the Week 6 visit, participants will provide final stool samples for gut microbiome analysis, and a blood sample for CyTOF whole blood Immune Profile. ECOG performance status and adverse event data will be obtained from EHR.

Official Title
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A Multi-center, 2-arm Observational Study Exploring the Role of the Gut and Tumor Microbiome in the Differential Immune Profile of Patients With Either Advanced ER-positive and HER2-negative Breast Cancer (Arm-1) or Advanced Melanoma Undergoing PD-1 Checkpoint Inhibitor Therapy (Arm-2) as Part of Standard of Care Treatment.

Conditions
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Breast Cancer, Melanoma

Intervention / Treatment
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* Other: Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Arm-1: Advanced ER-positive and HER2-negative Breast Cancer Signed, written, voluntary, and informed consent Histological confirmation of advanced ER positive and HER2 negative breast cancer Fresh frozen tumor DNA sequencing has been completed by selected NGS vendor(s) at the time of or prior to treatment initiation Female participants between 18 - 85 years of age ECOG performance status that is equal to 0 or 1 at the time of screening. Must be willing to provide blood for immune profile analysis on study enrollment and at specified study time points Must be willing and able to perform stool sample collection Participants due to receive first-line therapy with palbociclib and letrozole or palbociclib and fulvestrant Arm-2: Advanced Melanoma Signed, written, voluntary, and informed consent Histological or cytological confirmation of unresectable Stage III or unresectable Stage IV melanoma Fresh frozen tumor DNA sequencing has been completed by selected NGS vendor(s) at the time of or prior to treatment initiation Adults aged between 18 and 85 years old ECOG performance status that is equal to 0 or 1 at the time of screening Participants due to receive first-line systemic treatment with PD-1 checkpoint inhibitor therapy Must be willing to provide blood for immune profile analysis Must be willing and able to perform stool sample collection Exclusion Criteria: Arm-1: Advanced ER-positive and HER2-negative Breast Cancer Adult males Mental incapacity, as determined by an investigator Participant is pregnant, breastfeeding, or plans to become pregnant during the course of the study Experiencing active brain metastasis/metastases Active participation in an immuno-oncology or interventional clinical trial Participation in any experimental trial in the 3 months prior to screening Participant has relapsed on prior endocrine therapy for this instance of cancer, or has discontinued any prior adjuvant endocrine therapy within 6 months of screening History of inflammatory bowel disease, chronic diarrhea or malabsorption syndromes, or significant prior bowel resection as judged by the study investigator Use of immunosuppressants, including steroids, within 4 weeks of the first sample collection Oral or intravenous antibiotic usage within 3 months of the first sample collection Arm-2: Advanced Melanoma Diagnosis of uveal or mucosal melanoma Mental incapacity, as determined by an investigator Participant is pregnant, breastfeeding, or plans to become pregnant during the course of the study Experiencing active brain metastasis/metastases Active participation in an immuno-oncology or interventional clinical trial Participation in any experimental trial in the 3 months prior to screening History of inflammatory bowel disease, chronic diarrhea or malabsorption syndromes, or significant prior bowel resection as judged by the study investigator Use of immunosuppressants, including steroids, within 4 weeks of the first sample collection Oral or intravenous antibiotic usage within 3 months of the first sample collection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| Arm 1: Advanced ER-positive and HER2-negative Breast Cancer<br>Advanced ER+ and HER2- breast cancer participants due to receive standard of care first-line therapy with palbociclib and letrozole or palbociclib and fulvestrant. | Other: Observation<br>* No Intervention<br>|
| Arm 2: Advanced Melanoma<br>Unresectable Stage III or unresectable Stage IV melanoma participants due to receive first-line systemic treatment with PD-1 checkpoint inhibitor therapy. | Other: Observation<br>* No Intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interaction between the gut microbiome, tumor microbiome and serum immune profile for patients with advanced ER-positive and HER2-negative breast cancer or advanced melanoma. | Microbiome data obtained from fecal samples will be compared using alpha and beta diversity metrics. | Screening, week 2, week 4, week 6 |