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Cetuximab + motolimod is a combination investigational therapy evaluated primarily for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is an epidermal growth factor receptor (EGFR) monoclonal antibody that blocks EGFR signaling, inhibiting tumor cell growth and survival. Motolimod (VTX-2337) is a small molecule agonist of toll-like receptor 8 (TLR8), which is expressed on myeloid dendritic cells, monocytes, and NK cells. Motolimod stimulates the innate immune response by activating TLR8, inducing production of cytokines and chemokines, which are thought to modulate the tumor microenvironment and enhance anti-tumor immunity. Clinical trials (e.g., the Active8 trial) showed the combination was well tolerated but showed improved outcomes mainly in patient subsets such as those with HPV-positive tumors. The standard EXTREME regimen includes platinum chemotherapy, fluorouracil, and cetuximab; motolimod is added as immune-modulating therapy[1][2][3][5][7].
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