A phase I trial published on Lancet Oncology, showed that a combination of anti PD-1 and CD40 agonist, added to gemcitabine and nab-paclitaxel, led to 60% of response rate, with some durable responses, although the clinical benefit of adding a CD40 agonist to an anti PD-1 plus chemotherapy as first-line in patients with metastatic PDAC, was not confirmed in a phase 2 randomized trial.58 59 In addition, the inhibition of the CXCL12/CXCR4 axis has been demonstrated to modify the immunosuppressive TME of patients with PDAC and colorectal cancer.60 61. Here, CXCL12 is linked to colorectal cancer.