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HRS-4642 + nimotuzumab is an investigational combination therapy consisting of HRS-4642, a long-acting, liposome-formulated, non-covalent small-molecule inhibitor of KRAS G12D, and nimotuzumab, a humanized monoclonal antibody targeting the epidermal growth factor receptor (EGFR). This combination is designed to simultaneously inhibit mutant KRAS G12D and block EGFR signaling, a strategy aimed at overcoming or preventing resistance to KRAS G12D monotherapy. Preclinical studies have shown that nimotuzumab synergizes strongly with HRS-4642, sustaining suppression of the MEK/ERK pathway and reversing acquired resistance. The combination is being evaluated in clinical trials, including Phase Ib/II and Phase II studies, for the treatment of KRAS G12D-mutant pancreatic cancers, such as recurrent or metastatic pancreatic ductal adenocarcinoma (PDAC) and borderline resectable pancreatic adenocarcinoma, both as a chemotherapy-free regimen and in combination with gemcitabine and nab-paclitaxel (AG regimen).
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