Search

In the phase 3 CheckMate 459 study (NCT02576509), first-line nivolumab (NIVO) treatment demonstrated higher overall response rate (ORR) and a favorable safety profile, but no significant improvement in overall survival (OS) compared with sorafenib (SORA) in patients with advanced hepatocellular carcinoma (HCC). Here, we report exploratory biomarker analyses from the trial with a potential to identify patients who may benefit from NIVO. Archival or fresh tumor samples were collected before treatment and subjected to whole exome sequencing (WES) (400/730: 55%) for genetic alterations including high microsatellite instability (MSI-H) and WNT/beta-catenin pathway components, as well as whole transcriptome RNA sequencing (469/730: 64%) for analysis of individual genes, inflammation signatures and Gene Set Enrichment Analysis (GSEA). Associations between biomarkers and best overall response (BOR), progression free survival (PFS) and OS were evaluated at a minimum follow-up of 33·6 months. RNA sequencing analysis demonstrated that high Gajewski inflammation gene signature score of ≥0.47 (30% of tumors) was associated with an improvement in BOR (p=0.0043), PFS (p=0.00065) and OS (p=0.0073) within the NIVO arm only. Upon comparison of NIVO versus SORA, only patients whose tumors were inflammation high demonstrated NIVO benefit for BOR (p=0.017), PFS (p=0.0063) and OS (p=0.037). Responses to NIVO were associated with higher expression of CD8A, CD8B, PDCD1 (PD-1) and other inflammation-associated genes within the tumor (false discovery rate, FDR Citation Format: Jaclyn Neely, Jin Yao, Masatoshi Kudo, Richard S. Finn, Bruno Sangro, Ignacio Melero, Anthony El-Khoueiry, Marina Tschaika, Damir Begic, Ashwin Sama, Parul Doshi, Thomas Yau, Robin Kate Kelley. Genomic and transcriptomic analyses related to the clinical efficacy of first-line nivolumab in advanced hepatocellular carcinoma from the phase 3 CheckMate 459 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2145.