156 Background: The detection of circulating nucleic acids using non-invasive blood-draws has become highly relevant to clinical testing. In this study we report on the development of a blood-based PD-L1 test for immunotherapy selection. Methods: We have previously reported on the analytic performance of a droplet digital™ PCR (ddPCR) assay for circulating cytokeratin 19 and PD-L1. Using a variable threshold based on a logistic regression score for the blood assay and a 1% IHC (immunohistochemistry) tissue cut-off, concordance was 80% (n = 16). Positive calls for the blood-based PD-L1 assay ranged from 2 to 124 copies. In this study we focused on variables that could impact concordance of the blood assay and tissue results. Criteria included droplet counts for tissue and blood mRNA transcripts and tumor proportion score (TPS) for the tissue IHC assay (22C3 pharmDx). Results: We examined the correlation between PD-L1 in formalin-fixed paraffin-embedded (FFPE) tissue by IHC, mRNA expression in serial cut FFPE sections, and in matched plasma samples collected at the time of tissue resection. Five cases were assayed to confirm PD-L1 positivity by tissue. We successfully recovered RNA from serial tissue sections for each case and detected PD-L1 levels ranging from 6 to 1272 copies. Plasma samples were available for four of the cases for circulating RNA evaluation, and we were successful in detecting PD-L1 in all cases (copy range 32-138). While all four cases contained detectible PD-L1 mRNA in tissue and circulation, we observed little concordance between these levels in tissue and blood. Conclusions: We have developed methods to measure the dynamic range of PD-L1 from plasma. We have shown feasibility of these methods by evaluating key immune and cancer-specific RNAs. The current study demonstrates that although the development of quantitative assays for mRNA in blood is possible, concordance with traditional clinical tissue assays such as IHC may not be a useful validation measure. We have initiated prospective validation studies that will continue to evaluate PD-L1 expression by IHC and in the blood-based assay, and will also monitor patient performance measures in response to immunotherapy.