Abstract CT178: Prevalence of PD-L1 expression in 1st-line (1L) locally advanced/unresectable or metastatic urothelial carcinoma (UC)
Authors: Grivas Petros , Morgans Alicia K. , Lotan Yair , Gregg Jeffrey , Geynisman Daniel , Friedlander Terence , Agarwal Piyush K. , Tesic-Schnell Marija , Bernstein Andrew , Makari Doris , Meeks Joshua J. 
Published: August 2019

Abstract
Background: Treatments for 1L advanced, unresectable, or metastatic UC include platinum-based chemotherapy, immune checkpoint blockade, or clinical trial enrollment. Not all patients benefit from, or are eligible for, specific therapies due to comorbidities and performance status. There is an urgent need for biomarker-directed strategies to enable patient selection and improve outcomes. Currently the only clinically used molecular biomarker is programmed cell death ligand-1 (PD-L1) protein expression in tumor tissue. Although variably defined with different assays, higher PD-L1 expression generally correlates with increased response rates to immune checkpoint blockade. Improved understanding of the prevalence and potential prognostic role of PD-L1 testing can further enhance its clinical utility and guide novel clinical trial designs.
Methods: This observational study will enroll 250 patients diagnosed with advanced UC either prior to or during 1L therapy, as initiated at the discretion of participating clinicians from 60 US community sites. The primary endpoint is prevalence (with exact [Clopper-Pearson] 95% CI) of PD-L1 high expression by VENTANA SP263 Assay on pretreatment tumor tissue (classified as PD-L1 high if ≥25% of tumor cells [TCs] exhibit staining; or if immune cells [IC] present &gt;1% and IC with staining ≥25%; or IC present =1% and IC with staining =100%). Secondary endpoints include the association of pretreatment PD-L1 expression with pretreatment tumor tissue mutational burden (tTMB), descriptions of treatment response and outcomes (objective response rate based on RECIST 1.1, progressive-free survival [PFS], and overall survival [OS]) and assessment of their correlations with PD-L1 expression. Exploratory endpoints include the association of pretreatment tumor tissue PD-L1 with pretreatment blood-based tumor mutational burden (bTMB), changes in circulating tumor DNA levels, the correlation between tTMB and bTMB values, and the association of those biomarkers with PFS and OS. Enrollment will take place over 24 months. Patients will be followed for up to 30 months after enrollment. With 250 patients, the 95% CI for 30%, 45%, and 60% observed prevalence of PD-L1 high expression are (24.4%, 36.1%), (38.9%, 51.2%), and (53.6%, 66.1%), respectively; the various secondary and exploratory analyses will be descriptive.
Citation Format: Petros Grivas, Alicia K. Morgans, Yair Lotan, Jeffrey Gregg, Daniel Geynisman, Terence Friedlander, Piyush K. Agarwal, Marija Tesic-Schnell, Andrew Bernstein, Doris Makari, Joshua J. Meeks. Prevalence of PD-L1 expression in 1st-line (1L) locally advanced/unresectable or metastatic urothelial carcinoma (UC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT178.