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

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

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 181

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Research Site
  • California
    • Glendale, California, United States, 91204
      • Research Site
    • Los Angeles, California, United States, 90048
      • Research Site
    • Los Angeles, California, United States, 90067
      • Research Site
    • Monterey, California, United States, 93940
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80211
      • Research Site
    • Englewood, Colorado, United States, 80113
      • Research Site
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Research Site
    • Stamford, Connecticut, United States, 06904
      • Research Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Research Site
    • Hialeah, Florida, United States, 33016-1815
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Research Site
    • Roswell, Georgia, United States, 30076
      • Research Site
  • Illinois
    • Geneva, Illinois, United States, 60134
      • Research Site
    • Harvey, Illinois, United States, 60426
      • Research Site
    • Lake Barrington, Illinois, United States, 60010
      • Research Site
    • Naperville, Illinois, United States, 60540
      • Research Site
  • Indiana
    • Greenwood, Indiana, United States, 46143
      • Research Site
    • Lafayette, Indiana, United States, 47904
      • Research Site
    • Muncie, Indiana, United States, 47303
      • Research Site
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Research Site
    • Waterloo, Iowa, United States, 50703
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
    • Wichita, Kansas, United States, 67226
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Research Site
    • Shreveport, Louisiana, United States, 71106
      • Research Site
  • Maine
    • Brewer, Maine, United States, 04412
      • Research Site
    • Lewiston, Maine, United States, 04240
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503-2563
      • Research Site
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Research Site
    • Saint Cloud, Minnesota, United States, 56303
      • Research Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Research Site
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
      • Research Site
    • East Brunswick, New Jersey, United States, 08816
      • Research Site
    • Englewood, New Jersey, United States, 07631
      • Research Site
    • Freehold, New Jersey, United States, 07728
      • Research Site
    • Little Silver, New Jersey, United States, 07739
      • Research Site
    • Mount Laurel, New Jersey, United States, 08054
      • Research Site
  • New York
    • Albany, New York, United States, 12206
      • Research Site
    • Johnson City, New York, United States, 13790
      • Research Site
    • Port Jefferson Station, New York, United States, 11776
      • Research Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site
    • Kettering, Ohio, United States, 45429
      • Research Site
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
    • Nashville, Tennessee, United States, 37209
      • Research Site
  • Texas
    • Temple, Texas, United States, 76508
      • Research Site
    • The Woodlands, Texas, United States, 77380
      • Research Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Research Site
  • Washington
    • Olympia, Washington, United States, 98502
      • Research Site
    • Renton, Washington, United States, 98055
      • Research Site
    • Seattle, Washington, United States, 98101
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site
    • Wenatchee, Washington, United States, 98801
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patient population with care managed in a community setting in the United States

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients diagnosed with advanced urothelial carcinoma; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB	bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Results for TMB can range from 0 (non-shedder) to very high values >50 mut/Mb (no maximum has been determined). The results for pre-treatment bTMB will be presented by PD-L1 results (high vs low).	24 months
To assess changes in ctDNA levels (variant allele fractions [VAFs]) at 3 points of sample testing: (1) Before starting 1L treatment (pre-treatment) (2) before initiating treatment on day 1 of cycle 3, and (3) at the time of progression (if applicable)	ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. VAF is the relative frequency of alleles at a particular locus in a population, expressed as a percentage, ranging from 0.3% to 100%. Changes in ctDNA levels at 3 points of sample testing will be assessed.	60 months
To examine the correlation between pre-treatment tTMB and bTMB values	bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Assay results for pre-treatment tTMB will be assessed by pre-treatment bTMB results.	24 months
To assess the prognostic value of pre-treatment and changes to ctDNA levels, and pre-treatment tTMB compared to bTMB, for outcomes of ORR, PFS, and OS	bTMB and ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Objective response, PFS, and OS (defined in secondary outcome measures) will be assessed by the following: changes to ctDNA levels (VAFs) at 3 timepoints (defined above); and pre-treatment tTMB assay results compared with pre-treatment bTMB assay results.	60 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Chair: Petros Grivas, MD, University of Washington; Study Chair: Joshua Meeks, Northwestern University

Publications and helpful links

Helpful Links

• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): January 12, 2022
• Study Completion (Actual): May 25, 2023

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: December 23, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; Registry
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: D419BR00008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No