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A Phase 1 trial enrolled 46 patients with first recurrence glioblastoma (GBM) who had previously received standard surgery, radiation, and temozolomide. The study was designed prior to 2016, so 6 of the 46 patients included had IDH mutations. The researchers tested relatlimab, an antibody that blocks LAG-3, an immune checkpoint that acts as another "brake" on exhausted T cells. Half the patients received relatlimab alone, while the other half received it with nivolumab (Opdivo), a PD-1 checkpoint inhibitor. Although Opdivo has previously failed as a monotherapy to improve survival in GBM trials, combining it with LAG-3 blockade may help overcome some of the immune suppression seen in GBM. The study's primary goal was safety, which was achieved. While the trial was not designed to prove efficacy, the one-year survival was 52.2% with the combination versus 34.8% with relatlimab alone, and researchers found evidence of increased immune-cell infiltration into tumors. It is also worth noting that the five patients who survived longer than two years were in the combination therapy group. A randomized Phase 2 trial is now underway to determine whether the combination improves outcomes.