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NOX-A12 + pembrolizumab + nanoliposomal irinotecan + fluorouracil + leucovorin is an investigational combination regimen being evaluated for the treatment of second-line metastatic pancreatic cancer, specifically in patients with microsatellite-stable (MSS) disease. The regimen combines olaptesed pegol (NOX-A12), an L-RNA aptamer that neutralizes the chemokine CXCL12 to disrupt the protective tumor microenvironment and promote T-cell infiltration, with pembrolizumab, an anti-PD-1 monoclonal antibody that blocks the PD-1/PD-L1 checkpoint pathway to restore T-cell-mediated anti-tumor immunity. This immunotherapy backbone is combined with a chemotherapy regimen consisting of nanoliposomal irinotecan (Onivyde), fluorouracil (5-FU), and leucovorin (folinic acid), which provides cytotoxic anti-tumor activity. Developed by TME Pharma in collaboration with Merck & Co. (MSD), this combination is being evaluated in the Phase 2 OPTIMUS clinical trial (NCT04901741) to overcome the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma and enhance the efficacy of immune checkpoint inhibition.
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