Genomic and immune landscape of metastatic melanoma (MM) treated with pembrolizumab (PEM).

184Background: Predictive biomarkers for PEM in MM is an active area of research. Methods: INSPIRE (NCT02644369) is a biomarker-driven Princess Margaret Cancer Centre initiative to evaluate genomic and immunologic changes in tumor and blood of patient (pts) treated with PEM at 200 mg IV Q3W. Baseline (BL) and on treatment (post 2-3 doses of PEM) fresh tumor biopsies were collected for DNA/RNA sequencing, immune-profiling, and tumor PD-L1 expression by immunohistochemistry (QualTek), with longitudinal blood collection for immunophenotyping. Results: As of 9/2017, 11 MM pts (9 cutaneous, 1 choroidal, 1 mucosal) were enrolled. Median treatment duration was 6 months (0.75 – 14.25); 7 pts remain on study. 7/11 (64%) pts had partial response (PR), 3/11 (27%) progressive disease (PD) and 1 was not evaluable (NE) per RECIST 1.1. Based on data for 8 pts (6 PR, 2 PD), higher percentage (%) PD-1 (mean 70 vs 12%), TIGIT (82 vs 43%) and 4-1BB (23 vs 4%) positivity on CD8 T cells in tumor vs blood was seen (all p < 0.0...