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454 Background: According to population-based studies, there is a significant racial difference in patient characteristics, incidence, and survival among bladder cancer patients. Non-Hispanic whites have the highest incidence rate, followed by blacks. However, racial clinical trial disparities in clinical research are a critical problem around the world, with an underrepresentation of the black population. In the last years, multiple phase 2/3 trials have introduced the use of immunotherapy and targeted therapy in the treatment of bladder cancer. We aimed to assess the enrollment disparities in pivotal BC clinical trials. Methods: Published clinical trials were identified from the Bladder Cancer European Society of Medical Oncology (ESMO) guideline, considering the approved drugs and availability in clinical practice. The characteristics of participants, including race and geographic location, were collected. Results: A total of 1 phase 2 or 3 trials were identified, evaluating pembrolizumab, atezolizumab, avelumab, erdafitinib, durvalumab +/- tremelimumab and enfortumab vedotin, with a total of 7748 patients. The table summarizes the findings. Race information is available only in 8 of them, 4 in the original report and 4 in the results section of clinicaltrials.gov, with a pooled sample of 6573 patients. White, Asian and Black patients comprised 71.74% (4716 pts), 19.9% (1313 pts), and 0.66% (44 pts) of all patients, respectively. The percentage of white patients ranged from 51.6% to 88.6%, whereas the black population varied from 0.3% to 2.2%. Geographical location information is available only for 2 clinical trials, with a predominance of patients from the United States and Europe and an under-representation of patients from other continents. Conclusions: We observed a low rate of race reporting in bladder cancer published trials and a very significant under-representation of non-white participants in the pivotal trials for bladder cancer, with just 0.66% of black patients. Based on these finding, there are insufficient data to confirm the effectiveness or safety of new drugs in minority groups, especially blacks. To provide generalizable results, race reporting should be always included in licensing trials, and recruitment of black and other minority population to trials should be stimulated.[Table: see text]

552 Background: The possibility to predict the pathologic complete response (pT0) or downstaging (pT≤1) after neoadjuvant therapy may have profound impact on the management of MIBC and orient next-generation bladder-sparing trials. The VIRADS is a standardized reporting system that uses mpMRI parameters to predict the probability of MIBC. No studies have analyzed the ability of VIRADS to predict the pT0 or pT≤1 response post-immunotherapy (IO). Methods: In PURE-01 patients (pts) were staged with bladder multiparametric magnetic resonance imaging (mpMRI: T2-weighted imaging, diffusion-weighted imaging, dynamic contrast enhancement) before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VIRADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VIRADS scores were dichotomized between 0-3 and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Results: In total, 58 pts were had centrally-reviewed MRI scans (N=116 mpMRI), treated between 02/17 and 08/18. Demographic characteristics and outcomes were generally similar between the all-treated and VIRADS-evaluable populations of PURE-01. Median age was 65 years, 52 (89%) had pure/predominant urothelial carcinoma (UC) histology, 25 (43.1%) had cT3-4N0 MIBC. Pre-pembro: 8 pts (13.8%) had no measurable disease (VIRADS=0), 20 (34.5%) a VIRADS 1-3 score, and 30 (51.7%) had a VIRADS 4-5 score. Six pts (10.3%) had a downstage from VIRADS 4-5 to VIRADS 0-3 post-pembro. Both pre-pembro and post-pembro VIRADS 0-3 scores were significantly associated with pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VIRADS 0-3 against pT≤1 response (OR: 30.2, 95%CI: 6.2-223.2, p

549 Background: The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC; cT2–3N0M0; PMID 30343614). We have previously reported that specific molecular subtypes (i.e. basal or claudin-low) and immune signatures are associated with more favorable survival. However, reports on the detailed tumor biology of patients (pts) who relapsed after neoadjuvant pembrolizumab are lacking. Herein, we provide a detailed characterization of relapsing pts and identify distinct gene expression patterns with potential utility as novel biomarkers. Methods: Microarray data from transurethral resection of the bladder tumor (TURBT; N=102) and matched RC (N=25) tissue from the PURE-01 trial were analyzed. Gene expression signatures and molecular subtypes were assigned as previously described (PMID 32165065). The Kaplan-Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of 0.05. Results: Differential gene expression analysis identified KRT20 and H19 to be enriched in relapsing patients (both p