simlukafusp alfa + pembrolizumab

Simlukafusp alfa + pembrolizumab is an experimental combination of simlukafusp alfa (RO6874281, FAP-IL2v), a novel recombinant immunocytokine, and pembrolizumab, a programmed death-1 (PD-1) checkpoint inhibitor. Simlukafusp alfa is an engineered antibody-IL-2 variant fusion protein that targets fibroblast activation protein (FAP) expressed on cancer-associated fibroblasts, resulting in localized activation of the immune system within the tumor microenvironment while minimizing systemic IL-2 toxicity. Specifically, it selectively activates CD8 T cells and natural killer (NK) cells via IL-2Rβγ without stimulating regulatory T cells through IL-2Rα (CD25). Pembrolizumab blocks the PD-1 pathway and restores T cell-mediated anti-tumor activity. The combination has been studied in advanced/metastatic melanoma, but did not demonstrate meaningful clinical activity in patients who progressed on prior checkpoint inhibitors[1][3]. The combination remains investigational and is not approved for any indication.

Other names

FAP-IL2v + pembrolizumab