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HRS-4642 + paclitaxel protein-bound + gemcitabine is an investigational combination regimen consisting of HRS-4642, a selective, high-affinity, non-covalent KRAS G12D inhibitor, combined with a standard chemotherapy backbone of albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine (also known as the AG or GnP regimen). Developed by Hengrui Pharma, HRS-4642 is formulated as an intravenous liposomal nanoparticle to enhance tumor accumulation via the enhanced permeability and retention (EPR) effect, prolong target inhibition, and minimize systemic toxicities. By specifically binding to the KRAS G12D mutant protein, HRS-4642 blocks downstream MEK and ERK phosphorylation, inhibiting the MAPK signaling pathway that drives tumor cell proliferation and survival. The addition of the cytotoxic agents gemcitabine (a nucleoside metabolic inhibitor) and nab-paclitaxel (a microtubule inhibitor) provides synergistic antitumor activity. This combination is primarily being evaluated in Phase III clinical trials for the first-line, neoadjuvant, and adjuvant treatment of advanced, metastatic, or resectable pancreatic ductal adenocarcinoma (PDAC) harboring the KRAS G12D mutation.
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