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This combination therapy consists of the CYP3A inhibitor cobicistat, the nucleoside analog gemcitabine, and the microtubule inhibitor nab-paclitaxel (nanoparticle albumin-bound paclitaxel). Developed by the German Cancer Research Center (DKFZ), this regimen is being investigated in the Phase I IntenSify trial for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). The rationale for this combination is to use cobicistat to inhibit CYP3A-mediated metabolism and potential resistance mechanisms, thereby enhancing the pharmacokinetic profile and therapeutic efficacy of the standard-of-care chemotherapy backbone (gemcitabine and nab-paclitaxel). Gemcitabine acts as an antimetabolite that inhibits DNA synthesis, while nab-paclitaxel promotes microtubule assembly and stabilization, leading to cell cycle arrest and apoptosis.
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