LAUSR

Abstract Background Using comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) we compared the frequency of IO biomarkers in ACB, UBC and SCCB. We also report the interim results of neoadjuvant pembrolizumab in patients (pts) with muscle-invasive bladder cancer (MIBC) and variant histologies from PURE01 (NCT02736266). Methods Within FMI database, 143 cases of ACB, 2,142 cases of UCB and 83 cases of SCCB were subjected to CGP using a hybrid-capture based assay. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC using the Ventana SP-142 assay with >1% tumor cell or immunocyte (TILs) scoring positive. Among 96 pts of PURE01, 15 had predominant variant SCCB histology. Results ACB patients were younger and more often female than UBC and SCCB (P  /= 20 mut/Mb (P  Table . 930P Adenocarcinoma (ACB) Urothelial Carcinoma (UBC) Squamous Cell Carcinoma (SCCB) Cases 143 2,142 83 Median Age (Range) In years 58 (24-83) 67 (19-88) 62 (31-88) Males/Females 57/86 1597/545 45/38 GA/tumor 5.4 7.7 8.2 MSI High 2/106 (2%) 11/1661 (1%) 1/69 (1%) CD274 (PD-L1) gene amplification 0 (0%) 17 (1%) 4 (5%) Mean TMB 2.4 mut/Mb 9.9 mut/Mb 10.4 mut/Mb TMB >/= 10 mut/Mb 14 (10%) 697 (32%) 26 (31%) TMB >/= 20 mut/Mb 4 (3%) 243 (11%) 13 (16%) PD-L1 IHC Positive Tumor Cells 2/11 (18%) 76/244 (31%) 3/10 (30%) PD-L1 IHC Positive TILs 0/11 (0%) 74/244 (29%) 3/10 (30%) Conclusions Deep sequencing reveals significant differences in IO biomarkers among the 3 major types of bladder carcinomas. UBC and SCCB have higher frequencies of high TMB and PD-L1 expression than ACB and SCCB has the highest frequency of CD274amplification. Neoadjuvant pembrolizumab showed preliminary activity in SCCB. Further study of IO biomarkers in coordination with therapy response and inclusion of SCCB appear warranted in perioperative IO trials. Legal entity responsible for the study Foundation Medicine. Funding Foundation Medicine. Disclosure J.S. Ross: Full / Part-time employment: Foundation Medicine. S.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. A.B. Schrock: Full / Part-time employment: Foundation Medicine. R. Madison: Full / Part-time employment: Foundation Medicine. B.M. Alexander: Full / Part-time employment: Foundation Medicine. A. Necchi: Advisory / Consultancy: Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.