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A **combination regimen** of tebentafusp (a gp100×CD3 ImmTAC bispecific T-cell engager), durvalumab (a monoclonal antibody targeting PD-L1), and tremelimumab (a monoclonal antibody targeting CTLA-4), evaluated primarily for advanced or metastatic melanoma and tested in heavily pretreated patients. Tebentafusp redirects T-cells to gp100-positive melanoma cells (HLA-A*02:01-positive), while durvalumab and tremelimumab act as immune checkpoint inhibitors by blocking immune inhibitory pathways (PD-L1/PD-1 and CTLA-4, respectively) to enhance anti-tumor immune responses. Used together, this combination aims to improve immune-mediated tumor cell killing in patients previously treated with or relapsed after anti-PD(L)1 therapies. The safety profile of the triplet is consistent with the established profiles of the individual drugs, with no new safety signals. This combination is not currently an approved therapy but has demonstrated promising clinical activity, including improved tumor shrinkage and overall survival in phase 1b/2 studies for metastatic cutaneous melanoma[1][3][9].
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