Evaluation of predictive biomarkers for nivolumab in metastatic clear cell renal cell carcinoma (mccRCC) using RECIST and immune-related (IR) RECIST.

619Background: Development of predictive biomarkers would help select patients more likely to respond to nivolumab (nivo) in mccRCC. Here we evaluated biomarkers for nivo using endpoints based on either RECIST 1.1 (ORR and PFS) or irRECIST (irORR and irPFS), which were proposed to more accurately predict benefit of immunotherapy. Methods: We retrospectively analyzed tumor tissues from the Checkmate 010 trial (PMID: 25452452). PD-L1 expression on tumor cells (TC) was studied by IHC. Percentages of CD8+ tumor infiltrating cells (TIC) expressing the immune checkpoints PD1, TIM3 and LAG3 (either alone or in various combination) were determined by immunofluorescence (IF) and their predictive value assessed by the presence of a dose response relationship (DRR) with PFS or irPFS. The candidate biomarkers were then correlated with clinical outcomes using optimized cutoffs. Results: As previously shown, TC PD-L1 expression was not associated with PFS or ORR. In contrast, pts with TC PD-L1 ≥1% had longer median irP...