Detection of Early-Stage Pancreatic Ductal Adenocarcinoma From Blood Samples: Results of a Multiplex Biomarker Signature Validation Study

Randall E Brand, Jan Persson, Svein Olav Bratlie, Daniel C Chung, Bryson W Katona, Alfredo Carrato, Marién Castillo, Julie Earl, Arto Kokkola, Aimee L Lucas, A James Moser, Corinne DeCicco, Linda Dexlin Mellby, Thomas C King, Randall E Brand, Jan Persson, Svein Olav Bratlie, Daniel C Chung, Bryson W Katona, Alfredo Carrato, Marién Castillo, Julie Earl, Arto Kokkola, Aimee L Lucas, A James Moser, Corinne DeCicco, Linda Dexlin Mellby, Thomas C King

Abstract

Introduction: The IMMray PanCan-d test combines an 8-plex biomarker signature with CA19-9 in a proprietary algorithm to detect pancreatic ductal adenocarcinoma (PDAC) in serum samples. This study aimed to validate the clinical performance of the IMMray PanCan-d test and to better understand test performance in Lewis-null (le/le) individuals who cannot express CA19-9.

Methods: Serum samples from 586 individuals were analyzed with the IMMray PanCan-d biomarker signature and CA19-9 assay, including 167 PDAC samples, 203 individuals at high risk of familial/hereditary PDAC, and 216 healthy controls. Samples were collected at 11 sites in the United States and Europe. The study was performed by Immunovia, Inc (Marlborough, MA), and sample identity was blinded throughout the study. Test results were automatically generated using validated custom software with a locked algorithm and predefined decision value cutoffs for sample classification.

Results: The IMMray PanCan-d test distinguished PDAC stages I and II (n = 56) vs high-risk individuals with 98% specificity and 85% sensitivity and distinguished PDAC stages I-IV vs high-risk individuals with 98% specificity and 87% sensitivity. We identified samples with a CA19-9 value of 2.5 U/mL or less as probable Lewis-null (le/le) individuals. Excluding these 55 samples from the analysis increased the IMMray PanCan-d test sensitivity to 92% for PDAC stages I-IV (n = 157) vs controls (n = 379) while maintaining specificity at 99%; test sensitivity for PDAC stages I and II increased from 85% to 89%.

Discussion: These results demonstrate the IMMray PanCan-d blood test can detect PDAC with high specificity (99%) and sensitivity (92%).

Trial registration: ClinicalTrials.gov NCT03693378.

Conflict of interest statement

Guarantor of the article: Thomas C. King, MD, PhD

Specific author contributions: R.E.B, J.P., S.O.B, D.C.C., B.W.K, A.C., M.C., J.E., A.K, A.L.L, A.J.M., and C.D.: collection of specimens and drafting of manuscript. L.D.M.: planning of study and review of manuscript. T.C.K: planning and conducting of study, interpreting of data, and drafting of manuscript. All authors have approved the final draft.

Financial support: The collection of samples for this study was supported by a grant from Immunovia AB through the PanFAM Clinical Trial (ClinicalTrials.gov Identifier: NCT03693378) to Drs. Brand, Katona, and Chung.

Potential competing interests: Drs. Lucas and Brand have also been compensated by Immunovia AB or Immunovia, Inc for their participation in scientific/medical meetings as outside speakers. Dr. Mellby is an employee of Immunovia AB, and Dr. King is an employee of Immunovia, Inc.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Distribution of decision values in the 3 cohorts.
Figure 2.
Figure 2.
ROC curve comparison between PDAC (early-stage and all-stage PDAC) and the healthy and PanFAM cohorts. PDAC, pancreatic ductal adenocarcinoma; ROC, receiver operating characteristic.
Figure 3.
Figure 3.
Decision values from Commercial Test Model Study.
Figure 4.
Figure 4.
ROC curve for IMMray PanCan-d test performance in PDAC vs all controls, excluding samples with CA19-9 values of 2.5 U/mL or less. PDAC, pancreatic ductal adenocarcinoma; ROC, receiver operating characteristic.
Figure 5.
Figure 5.
ROC curve for samples with CA19-9

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