S5 High Performance of a Blood-Based Biomarker Test to Detect Early-Stage Pancreatic Cancer in a High-Risk Population, Across 2 Independent Clinical Validation Studies

Introduction: Early detection of pancreatic ductal adenocarcinoma (PDAC), has a significant impact on patient outcomes. Patients with known pathogenic genetic variants, family history predisposing them to PDAC, or presence of cystic neoplasms should undergo regular surveillance per clinical guidelines. Interval imaging, the current standard of care for these programs, can be costly, burdensome, and often with limited accuracy. We previously conducted 2 independent clinical validation studies (CLARITI, NCT06947382 and VERIFI, NCT06947395) where PancreaSure™, a serum-based early detection test for PDAC, showed high accuracy in differentiating early-stage disease vs high-risk control patients. We set out to determine test performance across both studies overall and in key patient sub-populations. Methods: Two multicenter, case-control, blinded studies were conducted to investigate the performance of PancreaSure™, a blood-based 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 pathogenic genetic variants, family history, or other clinical factors. Performance of the test in key sub-populations across studies was also investigated. Results: Across the 2 clinical validation studies, serum from 317 Stage I-II PDAC cases and 1134 high-risk controls were collected from 21 United States and 2 European sites. PancreaSure™ sensitivity and specificity overall was 78% and 92%, respectively. The test had significantly better sensitivity than CA19-9 alone in the individual studies and across both studies (66%, P < 0.001). PancreaSure™ showed high performance in key sub-populations (genetic/familial high-risk, patients diagnosed with diabetes, and those harboring small pancreatic cysts) across the 2 studies, with significantly higher sensitivity than CA19-9 overall (P < 0.05). Test performance in patients at high-risk for genetic/familial PDAC showed the highest specificity (94%). Conclusion: Across 2 independent clinical validation studies, PancreaSure™ showed high accuracy in differentiating Stage I and Stage II PDAC from high-risk controls in a large, pooled cohort. These results further support the robustness of the test’s performance and can serve as a tool for early-stage PDAC detection in patients of varying high-risk profiles.