Background:
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