PREVAIL: Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
Outcome Measures
Primary Outcome Measures
- 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
- 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)
- 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.
Other Outcome Measures
- To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB [24 months]
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).
- 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) [60 months]
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.
- To examine the correlation between pre-treatment tTMB and bTMB values [24 months]
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.
- 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 [60 months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of written informed consent
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Age ≥18 years old
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Patient must have advanced UC confirmed by their HCP; histologically- confirmed diagnosis of UC an dHCP-confirmed advanced UC.
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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).
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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.
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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
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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:
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Patients concurrently enrolled in other clinical trials that prohibit their participation in a non-interventional study
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Patient has resectable localized UC and has refused surgery
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Patients with history of non-urothelial active malignancy that completed therapy within 2 years from study enrollment except:
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Any resected in situ carcinoma or non-melanoma skin cancer
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Little Rock | Arkansas | United States | 72211 |
| 2 | Research Site | Glendale | California | United States | 91204 |
| 3 | Research Site | Los Angeles | California | United States | 90048 |
| 4 | Research Site | Los Angeles | California | United States | 90067 |
| 5 | Research Site | Monterey | California | United States | 93940 |
| 6 | Research Site | Santa Rosa | California | United States | 95403 |
| 7 | Research Site | Denver | Colorado | United States | 80211 |
| 8 | Research Site | Englewood | Colorado | United States | 80113 |
| 9 | Research Site | Hartford | Connecticut | United States | 06106 |
| 10 | Research Site | Stamford | Connecticut | United States | 06904 |
| 11 | Research Site | Boca Raton | Florida | United States | 33486 |
| 12 | Research Site | Hialeah | Florida | United States | 33016-1815 |
| 13 | Research Site | Jacksonville | Florida | United States | 32256 |
| 14 | Research Site | Augusta | Georgia | United States | 30912 |
| 15 | Research Site | Roswell | Georgia | United States | 30076 |
| 16 | Research Site | Geneva | Illinois | United States | 60134 |
| 17 | Research Site | Harvey | Illinois | United States | 60426 |
| 18 | Research Site | Lake Barrington | Illinois | United States | 60010 |
| 19 | Research Site | Naperville | Illinois | United States | 60540 |
| 20 | Research Site | Greenwood | Indiana | United States | 46143 |
| 21 | Research Site | Lafayette | Indiana | United States | 47904 |
| 22 | Research Site | Muncie | Indiana | United States | 47303 |
| 23 | Research Site | Cedar Rapids | Iowa | United States | 52403 |
| 24 | Research Site | Waterloo | Iowa | United States | 50703 |
| 25 | Research Site | Kansas City | Kansas | United States | 66160 |
| 26 | Research Site | Wichita | Kansas | United States | 67226 |
| 27 | Research Site | Baton Rouge | Louisiana | United States | 70809 |
| 28 | Research Site | Shreveport | Louisiana | United States | 71106 |
| 29 | Research Site | Brewer | Maine | United States | 04412 |
| 30 | Research Site | Lewiston | Maine | United States | 04240 |
| 31 | Research Site | Grand Rapids | Michigan | United States | 49503-2563 |
| 32 | Research Site | Duluth | Minnesota | United States | 55805 |
| 33 | Research Site | Saint Cloud | Minnesota | United States | 56303 |
| 34 | Research Site | Bridgeton | Missouri | United States | 63044 |
| 35 | Research Site | Las Vegas | Nevada | United States | 89106 |
| 36 | Research Site | Berkeley Heights | New Jersey | United States | 07922 |
| 37 | Research Site | East Brunswick | New Jersey | United States | 08816 |
| 38 | Research Site | Englewood | New Jersey | United States | 07631 |
| 39 | Research Site | Freehold | New Jersey | United States | 07728 |
| 40 | Research Site | Little Silver | New Jersey | United States | 07739 |
| 41 | Research Site | Mount Laurel | New Jersey | United States | 08054 |
| 42 | Research Site | Albany | New York | United States | 12206 |
| 43 | Research Site | Johnson City | New York | United States | 13790 |
| 44 | Research Site | Port Jefferson Station | New York | United States | 11776 |
| 45 | Research Site | Greenville | North Carolina | United States | 27834 |
| 46 | Research Site | Cincinnati | Ohio | United States | 45267 |
| 47 | Research Site | Kettering | Ohio | United States | 45429 |
| 48 | Research Site | Myrtle Beach | South Carolina | United States | 29572 |
| 49 | Research Site | Knoxville | Tennessee | United States | 37920 |
| 50 | Research Site | Nashville | Tennessee | United States | 37209 |
| 51 | Research Site | Temple | Texas | United States | 76508 |
| 52 | Research Site | The Woodlands | Texas | United States | 77380 |
| 53 | Research Site | Virginia Beach | Virginia | United States | 23462 |
| 54 | Research Site | Olympia | Washington | United States | 98502 |
| 55 | Research Site | Renton | Washington | United States | 98055 |
| 56 | Research Site | Seattle | Washington | United States | 98101 |
| 57 | Research Site | Tacoma | Washington | United States | 98405 |
| 58 | Research Site | Wenatchee | Washington | United States | 98801 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Chair: Petros Grivas, MD, University of Washington
- Study Chair: Joshua Meeks, Northwestern University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D419BR00008