Abstract 6669: Antigen features are associated with response and survival after neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer

Abstract In the Phase II LCCC1520 trial, neoadjuvant chemo-immunotherapy (pembrolizumab with gemcitabine plus cisplatin) induced response in 22 of 39 muscle-invasive bladder cancer patients[1]. In this correlative analysis, we identify molecular features associated with response and survival. Associations of molecular subtype, TMB, and antigen presentation and immune checkpoint gene expression with response and survival were evaluated pre-and post-treatment. Neoantigens were predicted in 4 immuno-oncology data sets (LCCC1520, IMvigor210 cohorts 1[2] and 2[3], and Hugo[4]) using Landscape of Effective Neoantigens Software[5]. Effective neoantigen count (ENC) was calculated by binning predicted neoantigens by expression, binding affinity, binding stability, and tumor PD-1 and PD-L1 expression, then identifying the bin in which neoantigen count was most strongly associated with response in the discovery set. Using elastic net modeling with 10-fold cross-validation, survival was predicted from immune gene signature expression, clinical variables, TMB and ENC. Response was associated with pre-treatment molecular subtype and immune checkpoint expression. Pre-treatment ENC was associated with response in Hugo (discovery set, p = 0.020) and the three validation sets (p = 0.011, 0.042, 0.049). The final elastic net model (Cox P-H p = 5.6e-5) predicted survival significantly better than TMB (p = 0.055) or ENC (p = 0.141) alone. Post-treatment antigen presentation gene expression was associated with survival among non-responders. We identify pre-and post-treatment features associated with response and survival in the LCCC1520 trial and propose that tumor antigen presentation is a major driver of neoadjuvant chemo-immunotherapy outcomes. [1] Rose JCO 2022 [2] Balar Lancet 2017 [3] Mariathasan Nature 2018 [4] Hugo Cell 2016 [5] Vensko bioRxiv 2022 Citation Format: Wolfgang Beckabir, Steven Vensko, Alec Wilkinson, Gatphan Atassi, Mi Zhou, Kenneth Fowler, Leah Flick, Hsing-Hui Wang, Mark Woodcock, Karen McKinnon, Jonathan Serody, Tracy Rose, Matthew Milowsky, William Kim, Benjamin Vincent. Antigen features are associated with response and survival after neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6669.