Nivolumab + Relatlimab Shows 22% Intracranial Response in PD-1–Refractory Melanoma Brain Mets

In the Phase I/IIa RELATIVITY-020 trial (NCT01968109), nivolumab (anti-PD-1) plus relatlimab (anti-LAG-3) was evaluated in 27 heavily pre-treated patients with measurable melanoma brain metastases. All patients received prior PD-1-directed treatment, 44% received prior ipi + mivo, and 81% had prior brain radiotherapy. Blinded central review confirmed an intracranial ORR of 22% (1 CR, 5 PR) and a clinical benefit rate of 63%; Median duration of CNS response and the median time to intracranial progression were not reached after ≥54 months, leaving 63% event-free >3 years. Median OS was 21.5 months (1-yr 70%, 3-yr 27%). Salvage ipilimumab monotherapy historically yields ~5% intracranial responses, while salvage ipilimumab + nivolumab reports ~22% ORR but ~55% grade 3-4 immune toxicity—higher than typically seen with the LAG-3 doublet, though detailed safety for this subset was not provided.