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Pembrolizumab + ipilimumab + aspirin is an investigational combination regimen consisting of two immune checkpoint inhibitors—pembrolizumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor)—and high-dose oral aspirin (cyclooxygenase 1 and 2 inhibitor), evaluated in phase II clinical trials primarily for advanced or metastatic melanoma. Pembrolizumab and ipilimumab enhance antitumor immunity by blocking inhibitory pathways on T cells, enabling enhanced immune response against malignant cells. Aspirin inhibits the cyclooxygenase pathway, reducing prostaglandin E2 (PGE2) synthesis and potentially amplifying the immunomodulatory activity of checkpoint inhibitors by affecting tumor immunity and inflammation. The regimen is being studied for its capacity to improve objective response rates beyond standard immunotherapy and is associated with increased risk of immune-related adverse events, especially with high-dose aspirin[1][2][3][5][6][7].
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