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HRS-4642 + gemcitabine + paclitaxel is an investigational combination regimen consisting of HRS-4642, a selective, high-affinity, non-covalent KRAS G12D inhibitor, and a chemotherapy backbone of gemcitabine and paclitaxel (typically administered as nab-paclitaxel, also known as the AG regimen). Developed by Hengrui Pharma, HRS-4642 is formulated as a liposomal nanoparticle for intravenous administration, which enhances tumor accumulation and prolongs target inhibition. By specifically binding to the KRAS G12D mutant protein, HRS-4642 inhibits downstream MEK and ERK phosphorylation, blocking the MAPK signaling pathway that drives tumor cell proliferation and survival. The combination of HRS-4642 with gemcitabine and paclitaxel is primarily being evaluated in clinical trials (including Phase III) for the first-line treatment of advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring the KRAS G12D mutation.
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