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

Completed

• Conditions: Urothelial Carcinoma

• Registration Number: NCT03788746
• Lead Sponsor: AstraZeneca

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2018-11-27
• Study First Submitted QC: 2018-12-23
• Study First Posted: 2018-12-28
• Study Start: 2019-01-17
• Primary Completion: 2022-01-12
• Study Completion: 2023-05-25
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 181

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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)	60 months	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.
To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay	24 months	Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.
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	54 months	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)

Trial Locations

Locations (1)

Research Site; 🇺🇸 Wenatchee, Washington, United States