The findings of a multicentre, open-label, randomized phase II study demonstrate the efficacy of combined inhibition of the programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) immune checkpoints with nivolumab and ipilimumab, respectively, in patients with melanoma brain metastases. Of 36 patients who received combination immunotherapy, 16 (46%) had intracranial responses versus 5 (20%) of the patients who received nivolumab alone. Patients with neurological symptoms were assigned to a separate treatment group, of which only one patient (6%) had a response to nivolumab monotherapy. Patients receiving combination therapy had an increased risk of grade 3–4 adverse events (54%), versus 16% and 12% of patients receiving nivolumab alone.