MO2-11-1 [Encore]Biomarkers and clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma in CheckMate 040

Abstract Background Nivolumab (NIVO), a programmed death-1 (PD-1) inhibitor, is approved in several countries for sorafenib-treated patients (pts) with advanced hepatocellular carcinoma (aHCC) based on CheckMate040. We report findings on exploratory biomarker analyses. Methods In CheckMate040, pts with aHCC received NIVO regardless of programmed death ligand 1 (PD-L1) status and HCC etiology. Baseline tumor samples were analyzed by IHC for expression of PD-L1, PD-1, T-cell markers (CD3, CD4, CD8, FOXP3), and macrophages (CD68, CD163), and (in a subset of pts) by RNA sequencing for inflammatory signatures (ISs). Results were correlated with clinical outcomes: response (complete response [CR]/partial response [PR]/stable disease [SD]/progressive disease [PD]) and overall survival (OS). Associations with etiology and geographical region (non-Asia vs Asia) were assessed. Data cutoff: June 2018. Results In 184 pts with evaluable data, increased tumor cell PD-L1 expression was associated with response (CR+PR vs SD [P = 0.00009]; CR+PR vs PD [P = 0.0007]) and OS (P = 0.03), as was increased PD-1 expression (CR+PR vs SD [P = 0.05]; CR+PR vs PD [P = 0.009]; OS [P = 0.05]). Of the T-cell markers assessed, CD3 was associated with response (n = 182, CR+PR vs SD; P = 0.05). In pts positive for CD3 or CD8, there was a trend toward improved OS (P = 0.08). There was no association between CD68 and CD163 expression and clinical outcomes. For 37 pts with RNA sequencing data available, median Bristol-Myers Squibb (BMS) IS score was higher in pts with PR vs SD (P = 0.05) and was correlated with improved OS (P = 0.01). For all inflammation markers assessed, there was no association with etiology or geographical region. Conclusions In pts with aHCC, improved OS and response to NIVO may be associated with higher PD-L1, PD-1, and CD3 expression, and higher BMS IS scores, supporting the role of PD-1 inhibition in HCC treatment. Further investigation of these biomarkers is required. Originally presented at the AACR 2019.