Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the prevalence of pre-treatment tumor tissue PD-L1 expression in patients diagnosed with advanced urothelial carcinoma.

Detailed Description
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Advanced urothelial carcinoma (UC) (locally advanced/unresectable or metastatic UC) is a fatal disease with 5-year survival rate of 5%. The most frequently studied diagnostic for advanced UC is the programmed death-ligand 1 (PD-L1) protein expression in tumor tissue. A better understanding of PD-L1 expression in a real world setting could help understand its clinical utility in the management and decision making in advanced UC and clinical trial design

Official Title
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A Prospective, Non-Interventional Study to Assess the Prevalence of PD-L1 Expression in the First-Line Setting of Locally Advanced/Unresectable or Metastatic Urothelial Carcinoma

Conditions
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Urothelial Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent Age ≥18 years old Patient must have advanced UC confirmed by their HCP; histologically- confirmed diagnosis of UC an dHCP-confirmed advanced UC. Patient must be either currently receiving 1L systemic treatment for their advanced UC or will be starting 1L systemic treatment (i.e. newly diagnosed advanced UC; 1L therapy is defined as the first systemic therapy given for advanced UC). Patient remains eligible for the study if they received neoadjuvant or adjuvant platinum-based chemotherapy if their recurrence was more than 12 months after their last chemotherapy dose. Radio-sensitizing chemotherapy as part of chemoradiation is NOT counted as neoadjuvant or adjuvant chemotherapy; thus, the 12-month interval mention above does not apply, and the patient would be eligible Patients with available tumor tissue sample (fresh or archival - up to 3 years old) that was collected as part of SoC any time prior to 1L treatment for advanced UC with a target of 18 slides (7 minimum) available for biomarker testing (PD-L1 and tTMB). Already prepared slides must have been cut within 6 months prior to PD-L1 testing. Exclusion Criteria: Patients concurrently enrolled in other clinical trials that prohibit their participation in a non-interventional study Patient has resectable localized UC and has refused surgery Patients with history of non-urothelial active malignancy that completed therapy within 2 years from study enrollment except: Any resected in situ carcinoma or non-melanoma skin cancer Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy) and in which no systemic therapy was indicated

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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 |
| --- | --- |
| Patients diagnosed with advanced urothelial carcinoma<br>Patients with a confirmed diagnosis of advanced urothelial carcinoma, prior to or during first line therapy, who have available tumor tissue samples collected as part of standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples. | The proportion of advanced UC patients with biomarker PD-L1 high results will be calculated. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay | Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status. | 24 months | 
| To describe the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) as well as treatment patterns in the 1L setting of advanced UC | 1L advanced UC treatment patterns (such as regimen/agents used, start (first dose) and stop (last dose) dates, reasons for cis/carboplatin ineligibility) will be collected. Objective Response: complete or partial response based on healthcare provider (HCP) assessment; Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria highly recommended Progression: evidence malignancy has become worse or spreads in the body (based on HCP assessment). Objective response and survival endpoints (overall, stratified by PD-L1 expression [high vs. low] including the following: ORR: The proportion of patients with a complete or partial response based on HCP assessment; PFS: The time from the start of 1L advanced UC treatment until progression or death (any cause); and OS: The time from start of 1L advanced UC treatment until death (any cause) | 54 months | 
| To assess the association between pre-treatment tumor tissue PD-L1 expression with objective response, PFS, and OS among treated patients (anti PD-L1/PD-1, chemotherapy, other) | Objective response, PFS, and OS (defined above) will be stratified by pre-treatment tumor tissue PD-L1 expression, and among patients treated with anti-PD-L1/PD-1 or chemotherapy or other. | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urothelial Carcinoma, Registry