A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stroma and myeloid-rich microenvironment that confer resistance to immunotherapies. Previous studies demonstrated that disrupting the immune-stroma CXCR4-CXCL12 axis facilitates T cell recruitment and mobility to collaborate with anti-PD1/PD-L1 therapy. We sought to test the clinical viability of this immunotherapeutic strategy. 21 patients with metastatic PDAC were enrolled and treated in a phase 2 trial evaluating the effects of the plerixafor/AMD3100 and cemiplimab. Primary endpoint was objective response rate. Blood and tissue biospecimens were collected for correlative analyses. Parallel mouse studies were used to determine potential mechanisms of resistance. Treatments were well-tolerated, but only two patients demonst

SUBMITTER: Bever KM 

PROVIDER: S-EPMC12360203 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature