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Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial

Nature Medicine

Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM. Relatlimab monotherapy and the relatlimab–nivolumab combination were tolerable in this heavily pretreated population. Immuno-oncologic therapies targeting immune checkpoint molecules PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have not improved outcomes for GBM, although this strategy has substantially improved survival in many other cancer types. These data provide a clinical and translational foundation for further evaluation of LAG-3 blockade, with or without PD-1 blockade, in GBM.

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