Abstract B18: Exome scale liquid biopsy monitoring of putative neoantigens and genomic biomarkers in patients on anti-PD-1 therapy in squamous cell carcinoma of the head and neck
Authors: Abbott Charles W. , Bedi Nikita , Zhang Simo V. , Li Robin , Pyke Rachel Marty , Levy Eric , Chernock Rebecca , Mansour Mena , Sunwoo John B. , Colevas A. Dimitrios , Chen Richard , Boyle Sean M. 
Published: March 2020

Abstract
Monitoring treatment response and potential resistance mechanisms to therapy with typical liquid biopsy panels can be limited by the relatively small number of genes profiled. The limited scope can result in missed therapeutic biomarkers such as neoantigens, which may change dynamically with treatment, as well as potentially missed resistance mechanisms and pathways not typically covered by existing panels. To address these shortcomings, we applied an exome scale liquid biopsy monitoring platform, NeXT Liquid Biopsy, to analyze head and neck squamous cell carcinoma (HNSCC) patients who have received anti-PD1 therapy. Using this platform we sought to (1) identify and monitor neoantigen changes in cell free DNA (cfDNA) as a complement to tumor biopsy-derived neoantigens, (2) compare the differences in putative neoantigens identified in tissue and cfDNA, and (3) identify additional biomarker correlations between cfDNA and solid tumor biopsies. Pre- and post-intervention matched tumor, normal, and plasma samples were obtained from a pilot cohort of 9 patients with HNSCC. Following initial sample collection all patients received a single dose of nivolumab, followed by definitive resection of the primary tumor mass approximately one month later when possible, or a second biopsy where resection was impractical (resection, n=5; biopsy, n=4). Solid tumor and matched normal samples were profiled using ImmunoID NeXT, an augmented exome/transcriptome platform and analysis pipeline. For the plasma samples, we performed exome-scale cfDNA profiling with the ImmunoID NeXT Liquid Biopsy platform to detect somatic variants. Data from these two platforms were compared with corresponding clinical findings. We observed a strong concordance of somatic events between the plasma and tumor in both pre- and post-treatment timepoints. Median post-treatment neoantigen burden was reduced in solid tumor, but increased in cfDNA, when compared to pretreatment timepoints. HLA-specific loss of heterozygosity (LOH) was identified in a number of subjects, likely resulting in reduced neoepitope presentation in those cases. These changes were accompanied by increased immune cell infiltration in the tumor following treatment, with no changes to the CD8+/Treg cell ratio, suggesting consistent immunoregulatory influence. Exome-wide somatic events were reliably detected in cfDNA, providing additional potential biomarkers to complement biomarkers identified in solid tumor. As we increase our cohort size we expect that identification of biomarkers from both exome-scale tissue biopsy and cfDNA will provide a more comprehensive view into therapeutic response and resistance mechanisms in HNSCC patients missed with typical liquid biopsy panels.
Citation Format: Charles W. Abbott, Nikita Bedi, Simo V. Zhang, Robin Li, Rachel Marty Pyke, Eric Levy, Rebecca Chernock, Mena Mansour, John B. Sunwoo, A. Dimitrios Colevas, Richard Chen, Sean M. Boyle. Exome scale liquid biopsy monitoring of putative neoantigens and genomic biomarkers in patients on anti-PD-1 therapy in squamous cell carcinoma of the head and neck [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B18.