e23109 Background: Immune checkpoint inhibitors (IO) have become a powerful precision therapy option to treat advanced stage cancer with biomarkers such as PD-L1, tumor mutational burden (TMB), and microsatellite instability (MSI) associated with improved patient response rates. Despite this, many patients do not receive genomic testing for all IO biomarkers. Providence, a large US community health system, developed a pathologist-directed testing protocol where comprehensive genomic profiling (CGP) was routinely used at time of diagnosis for advanced cancer patients. Methods: Advanced cancer patients who received CGP (ProvSeq 523) and IHC testing for PD-L1 between 2019-2023 were included in the study. Patients were required to be treated at Providence and were assessed for presence of IO biomarkers and subsequent therapy selection. Real world data were curated from patient charts and genomic laboratory data by employing a novel natural-language processing (NLP) approach to accelerate abstraction. Results: The study included 2,502 patients (53% female, median age 68y, 83% white). Top 3 tumor types tested were lung (40%), colorectal (9%), and breast (8%). Overall, 58% (N = 1,455) of patients had presence of ≥1 IO biomarker, with 46% (N = 1,155) being PD-L1 positive, and 27% (N = 682) being TMB-H. In PD-L1 negative patients (N = 1,347; 54%), 300 (22%) were TMB-H and 18 (1%) were MSI-H. 53% (N = 767) of patients who harbored an actionable IO biomarker received IO-based therapy. Fewer patients with an IO biomarker received chemotherapy compared to patients without an IO biomarker (23% vs 35%, p &lt; 0.001). Patients who possessed ≥2 IO biomarkers received an IO precision therapy 68% of the time vs 47% in patients with 1 IO biomarker (p &lt; 0.001). In PD-L1 negative patients, 26% (N = 78) of TMB-H patients received IO monotherapy compared to 5% (N = 49) of TMB-L patients. Conclusions: IO biomarker presence is associated with increased precision therapy use. CGP identified many TMB-H patients for IO monotherapy that would have been missed with PD-L1 testing alone. More than half of patients eligible for IO therapy don’t receive it; ongoing analyses will evaluate the impact of pathology-directed reflex testing on IO as well as targeted therapy approaches. [Table: see text]

CGP-based IO biomarker assessment and treatment utilization across a major US health system.