High CXCR4 expression in pancreatic ductal adenocarcinoma is characterized by an inflammatory tumor phenotype with potential implications for an immunotherapeutic approach


Andreas Seeber, Florian Kocher, Andreas Pircher, Alberto Puccini, Yasmine Baca, Joanne Xiu, Kai Zimmer, Johannes Haybaeck, Gilbert Spizzo, Richard M. Goldberg, Axel Grothey, Anthony Frank Shields, Mohamed E. Salem, John Marshall, Michael J. Hall, Wolfgang Michael Korn, Chadi Nabhan, Francesca Battaglin, Heinz-Josef Lenz, Dominik Georg Friedrich Wolf


Single agent immune checkpoint inhibitors largely ineffective in pancreatic ductal adenocarcinoma (PDAC) (1).
C-X-C motifchemokinereceptor4(CXCR4)-CXCL12 axis modulates the immune tumor microenvironment (TME) in preclinical models (2)
BL-8040 (motixafortide) is a small synthetic peptide that binds CXCR4
blockade of which promotes T cell infiltration; is synergistic with anti-PD1 therapy in mouse models (3)
-COMBAT trial/KEYNOTE202: BL-8040 + pembrolizumab+/-chemotherapy (4)
-Cohort 1: 31 chemo-resistant pts treated, with BL8040+pembro: DCR=34.5%
-Cohort 2: 22 pts treated with BL8040+pembro+chemo: DCR=77% and mDoR=7.8m

Aim of the project: Describing the molecular and immunological landscape of CXCR4 PDAC

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