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**bifikafusp alfa + onfekafusp alfa + pembrolizumab** is a combination therapeutic regimen under investigation primarily for cutaneous T-cell lymphoma, malignant melanoma, and other skin cancers. - **bifikafusp alfa** is a recombinant fusion protein (L19-IL2) comprising the L19 antibody fragment linked to human recombinant interleukin-2, designed to target the extra-domain B of fibronectin on tumor vasculature, delivering immunostimulatory IL-2 directly to the tumor microenvironment. - **onfekafusp alfa** is a recombinant fusion protein (L19-TNF), using the same L19 antibody fragment linked to tumor necrosis factor-alpha, enabling targeted cytotoxicity and vascular disruption within tumors. - **pembrolizumab** is a monoclonal antibody targeting the programmed death-1 (PD-1) receptor on T-cells, blocking immune checkpoint inhibition and promoting anti-tumor T cell activity. The combination leverages tumor-targeted cytokine therapy (by L19-IL2 and L19-TNF) with immune checkpoint inhibition (by pembrolizumab) for a synergistic antitumor immune response, and is currently in Phase II clinical development for cutaneous T-cell lymphoma, with ongoing studies in various skin malignancies[5][8].
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