Performance of a blood-biomarker test for early detection of pancreatic ductal adenocarcinoma (PDAC) across all stages of disease versus a mixed control population.

659 Background: Early detection of pancreatic ductal adenocarcinoma (PDAC) has a significant impact on pancreatic cancer outcomes. Despite this, 4 in 5 patients are diagnosed at later disease stage where surgery is no longer an option. There is a need for more accurate and less burdensome testing methodology. We previously conducted two independent clinical validation studies (CLARITI and VERIFI) where PancreaSure, a serum-based early detection test for PDAC, showed high accuracy in differentiating early-stage disease versus high-risk control patients. To further understand the performance of the test across a varied patient population, we set out to determine test performance in Stage I-IV PDAC and in healthy controls. Methods: PancreaSure, a biomarker signature comprising a mathematical summation of ICAM-1, THSB1, CTSD, TIMP1, and CA19-9 values with a predefined cutoff to differentiate Stage I and Stage II PDAC from controls at high-risk due to genetic/familial background, was assessed for sensitivity and specificity in detecting Stage III and IV PDAC and in normal, healthy controls. Pooled analysis was conducted to determine weighted performance across all stages of PDAC and in high-risk and healthy controls. Results: The study comprised 317 Stage I-II (early stage) and 152 Stage III-IV (late stage) PDAC cases, 1134 high-risk controls, and 295 healthy controls that were collected from US and European sites. PancreaSure overall weighted sensitivity was 79.8% (73.3-86.4% 95% CI). Sensitivity was 77.6% (73.0-82.2%, 95% CI) in early-stage PDAC and 88.2% (81.8-93.0%, 95% CI) in late-stage PDAC. Overall weighted specificity was 90.8% (87.8-93.8% 95% CI). Specificity was 92.2% (90.6-93.7%, 95% CI) in high-risk controls and 97.7% (95.3-99.1%, 95% CI) in healthy controls. Conclusions: Across a robust clinical experience of almost 1900 patients, PancreaSure showed high accuracy across Stage I-IV PDAC, with improved performance in late-stage disease and in healthy controls. These results support the robustness of the test’s performance and can serve as a tool for both early-stage and late-stage PDAC detection in patients at high and normal risk of pancreatic cancer.