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**Vidutolimod + pembrolizumab** is an investigational combination therapy for advanced or metastatic melanoma, particularly in patients who are resistant to anti–PD-1 therapy. Vidutolimod is a first-in-class immunostimulatory biologic comprising a virus-like particle loaded with a CpG-A oligonucleotide acting as a Toll-like receptor 9 (TLR9) agonist; it is designed to stimulate plasmacytoid dendritic cells and induce local/systemic type I interferon–mediated antitumor immunity. Pembrolizumab is a monoclonal antibody that inhibits the programmed cell death protein 1 (PD-1) checkpoint, restoring T cell anti-tumor responses. The combination aims to convert "cold" tumors into "hot" tumors, overcoming immune resistance by inducing inflammation and enhancing T cell infiltration. Phase 1b trials have shown a promising objective response rate and durable responses in PD-1–blockade-resistant melanoma, with manageable safety profiles[1][2][3][4][5][6].
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