Pan-Tumor Genomic Biomarkers for PD-1 Based Immunotherapy

Tumor mutation burden (TMB) and a T-cell-inflamed gene expression profile (GEP) independently predict clinical outcome in pembrolizumab-treated patients in 22 indications and stratify distinct targets of resistance biology. ]]>
TMB was evaluated by whole exome sequencing (WES) of germline and tumor DNA from formalin-fixed paraffin-embedded (FFPE) pre-treatment samples in multiple cohorts of patients across the pembrolizumab clinical development program. The key inclusion criterion in our analysis dataset was the availability of sufficient DNA to perform sequencing. The initial discovery cohort for TMB was comprised of patients with PD-L1-positive head and neck squamous cell carcinoma (HNSCC) (KEYNOTE-012, B1 cohort, n=34), and the pan-tumor validation cohort consisted of patients with PD-L1-positive advanced solid tumors (n=119) from 2 multi-cohort trials (KEYNOTE-028, 17 cohorts, n=80, and KEYNOTE-012, A, C and D cohorts, n=39) across 20 cancer types. The HNSCC single-indication cohort included patients in the KEYNOTE-012, B1 cohort (n=34) and additional patients with PD-L1-unselected HNSCC from the KEYNOTE-012, B2 cohort (n=73). The melanoma single-indication cohort included patients with advanced melanoma from two studies KEYNOTE-001, n=30, and KEYNOTE-006, pembrolizumab arm, n=59. ]]>