Hybrid Capture-Based Next-Generation Sequencing (Hc Ngs) In Melanoma To Identify Markers Of Response To Anti-Pd-1/Pd-L1.

105Background: Agents blocking programmed death-1/ligand (aPD1) induce durable responses in many melanoma patients (pts). Greater numbers of somatic mutations have been linked to high aPD1 response rates (RR) in other cancers. We assessed whether number and/or type of mutations (mut) using HC NGS correlated with outcomes to aPD1 in melanoma. Methods: HC NGS on 236-315 genes was performed on archival samples from pts who received aPD1 (comprising ~1.25 megabases [MB]). A novel algorithm extrapolated genomic mutational load (ML) from this panel. Intratumoral T cell clonal expansion was determined by T cell receptor (TCR) sequencing. ML and TCR clonality were correlated with with aPD1 outcomes. Results: Responders to aPD1 had higher ML compared to non-responders in discovery (median 45.6 vs. 3.9 mut/MB; p=0.003, n=32), and validation cohorts (37.1 vs. 12.8 mut/MB; p=0.002, n=33). RR was superior in high ML pts compared to intermediate/low (Table) as was progression-free survival (PFS) (median not reached [MN...