68 Integrative biomarkers analysis from the phase 3 CheckMate 914 trial of nivolumab plus ipilimumab or nivolumab versus placebo for adjuvant clear cell renal cell carcinoma (ccRCC)

• DOI: 10.1136/jitc-2024-sitc2024.0068
• Publication Date: 2024-11-05T14:58:59Z
• Authors: Sai Vikram Vemula; Wenxin Xu; Aparajita Verma; Wiem Safta; Catherine Tang; Aparna Chhibber; David Paulucci; George Lee; Chung Wei Lee; Xiaowen Liu; Deepthi Chowbene; Nahuel Perrot; Paul Russo; Axel Bex; Viktor Grunwald; Toni K Choueiri; Saurabh Gupta; David F McDermott; Rupal Bhatt; Robert Motzer

<h3>Background</h3> There is an unmet need for predictive biomarkers immune check point inhibitors (ICI) in ccRCC. We previously showed that tumor PD-L1 expression and serum KIM-1 levels were independently associated with treatment effect adjuvant Nivolumab plus Ipilimumab (NIVO+IPI) vs placebo localized ccRCC Part A of Checkmate 914 (CM-914). Here we further investigated the role association response to NIVO+IPI B CM-914. In addition, explored a novel human-interpretable image feature-(IF) based platform biomarker identification. <h3>Methods</h3> Patients enrolled CM-914 (n=825) randomized post nephrectomy (Nx) receive NIVO+IPI, NIVO or as described.¹ used pre-treatment Nx samples assess PD-L1% cell (%TC) using IHC 28-8 pharm Dx assay. Assessment was performed Meso Scale Discovery (MSD) immunoassay (n=704) collected prior dosing on Cycle 1 Day (C1D1). IFs (n=1043) predict clinically relevant types (macrophages, neutrophils, lymphocytes, endothelial cells) molecular phenotypes from histopathology H&amp;E whole-slide images. The between clinical outcomes (DFS OS) by Kaplan-Meier (KM) Cox proportional hazards analysis. <h3>Results</h3> level &gt; 1% had improved DFS versus (HR=0.171 (0.036-0.823). When examining quartiles levels, subjects highest quartile baseline worse but not NIVO+IPI. IF analyses, PD-L1&gt;=1% higher macrophages, while cells PD-L1&lt;1%. Subjects fibroblasts lower microenvironment (TME) shorter <h3>Conclusions</h3> setting, &gt;=1% potentially favorable outcome elevated circulating are prognostic outcomes. Association specific types, identified provides initial characterization TME responsive patients <h3>Trial Registration</h3> NCT03138512. <h3>Reference</h3> Motzer RJ, <i>et al. Journal Clinical Oncology</i> 2024.