TLR9 and melanoma: This might clarify why vidutolimod is the sole TLR9 agonist that has demonstrated clinical activity as a monotherapy in advanced anti-PD-1 refractory melanoma patients.617 In contrast, the Phase III clinical trial involving the combination of CpG-C oligodeoxynucleotide tilsotolimod and ipilimumab failed to show improvements in advanced PD-1 blockade-refractory melanoma, potentially due to these distinctions (NCT03445533).