Exploring Relevant Immune-based Biomarkers and Circulating Tumor Cells During Treatment With Immunotherapy in Genitourinary Malignancies (CTC Immune Based Biomarkers)

Study Overview
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Brief Summary
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This pilot study purpose of this study is to describe peripheral circulating immune cell profiles at baseline and change on treatment with immune checkpoint inhibitors in renal cell carcinoma and urothelial carcinoma.

Official Title
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Exploring Relevant Immune-based Biomarkers and Circulating Tumor Cells During Treatment With Immunotherapy in Genitourinary Malignancies

Conditions
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Carcinoma, Renal Cell, Carcinoma, Urothelial

Intervention / Treatment
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* Device: Immune cell and CTC detection procedures


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group A Renal Cell Carcinoma: Patients will be eligible for inclusion in this study if ALL of the following criteria apply: Histologically confirmed or radiological diagnosis of renal cell carcinoma. Clear cell and non-clear cell carcinoma (such as papillary, chromophobe, collecting duct, and medullary) allowed. Evidence of locally advanced, high grade or metastatic disease in any site on most recent imaging scan Planned initiation of treatment with any of the following: Immune modulatory agent targeting any of the following: PD-1, PD-L1, CTLA-4, CD27, OX40, LAG3 or tumor infiltrating lymphocytes (TIL) Immune modulatory agent consisting of any of the following: CAR-T, bispecific antibody or vaccine trial. Age > 18 years. Ability to understand and the willingness to sign a written informed consent document. Group B Urothelial Carcinoma: Patients will be eligible for inclusion in this study if ALL of the following criteria apply: Histologically confirmed diagnosis of urothelial carcinoma. Non-transitional cell carcinoma (such as adenocarcinoma and squamous cell carcinoma) allowed. Evidence of locally advanced, high grade or metastatic disease in any site on most recent imaging scan Planned initiation of treatment with any of the following: Immune modulatory agent targeting any of the following: PD-1, PD-L1, CTLA-4, CD27, OX40, LAG3 or tumor infiltrating lymphocytes (TIL) Immune modulatory agent consisting of any of the following: CAR-T, bispecific antibody or vaccine trial. Age > 18 years. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: A patient will not be eligible for inclusion in this study if any of the following criteria apply: 1. History of intercurrent or past condition that would make participation in this protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s).

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 |
| --- | --- |
| Group A: Renal Cell Carcinoma<br>Subjects in Group A (patients with locally advanced, high grade or metastatic renal cell carcinoma starting immunotherapy) will have blood collected at baseline, at the time of a standard of care cytoreductive surgery (if applicable), 12 weeks, 24 weeks, 52 weeks and upon disease progression on treatment for analysis of peripheral blood mononuclear cells (PBMCs), circulating tumor cells (CTCs), metabolites, cytokines and angiokines. Urinary and fecal specimens will be collected at baseline, at the time of a standard of care cytoreductive surgery (if applicable), 12 weeks, 24 weeks, 52 weeks and upon disease progression. Tissue will be collected at the time of a standard of care cytoreductive surgery (if applicable). | Device: Immune cell and CTC detection procedures<br>* Immune cell profiling assays (in blood and archival tumor samples) and circulating tumor cell assays (in blood samples)<br>|
| Group B: Urothelial Carcinoma<br>Subjects in Group B (patients with locally advanced, high grade or metastatic urothelial carcinoma starting immunotherapy) will have blood collected at baseline, at the time of a standard of care cytoreductive surgery (if applicable), 12 weeks, 24 weeks, 52 weeks and upon disease progression on treatment for analysis of peripheral blood mononuclear cells (PBMCs), circulating tumor cells (CTCs), metabolites, cytokines and angiokines. Urinary and fecal specimens will be collected at baseline, at the time of a standard of care cytoreductive surgery (if applicable), 12 weeks, 24 weeks, 52 weeks and upon disease progression. Tissue will be collected at the time of a standard of care cytoreductive surgery (if applicable). | Device: Immune cell and CTC detection procedures<br>* Immune cell profiling assays (in blood and archival tumor samples) and circulating tumor cell assays (in blood samples)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of T-cells before and after treatment with immune therapies |  | Baseline and Disease progression (up to two years) | 
| Change in the number of B-cells before and after treatment with immune therapies |  | Baseline and Disease progression (up to two years) | 
| Change in the number of myeloid cells before and after treatment with immune therapies |  | Baseline and Disease progression (up to two years) | 
| Number of patients with detectable circulating tumor cells (CTCs) |  | Disease progression (up to two years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The prevalence of tumor-infiltrating lymphocytes for all subjects at baseline |  | Baseline | 
| The prevalence of tumor-associated macrophages for all subjects at baseline |  | Baseline | 
| The change in CTCs over time |  | Baseline, week 4, week 8, week 12 and progression (up to two years) | 
| The distribution of CTCs difference scores across the ordered tumor response categories of CR, PR, SD, and PD |  | Disease progression (up to two years) | 
| The change in tumor burden over time measured by RECIST |  | Baseline, Week 12, Progression (up to two years) |