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This combination therapy is an experimental front-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), currently being evaluated in a Phase 2 clinical trial sponsored by Yale University. The regimen integrates the PD-1-targeting monoclonal antibody pembrolizumab with a standard-of-care chemotherapy backbone of gemcitabine and nab-paclitaxel, supplemented by pegvorhyaluronidase alfa (PVHA). PVHA is a pegylated recombinant human hyaluronidase designed to degrade hyaluronan, a major component of the dense extracellular matrix in pancreatic tumors that creates high interstitial fluid pressure and impedes drug delivery. By depleting hyaluronan, PVHA aims to enhance the intratumoral concentration of the cytotoxic agents and facilitate the infiltration of pembrolizumab-activated T cells. Pembrolizumab functions as an immune checkpoint inhibitor, blocking the interaction between PD-1 and its ligands (PD-L1/PD-L2) to reinvigorate the anti-tumor immune response.
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