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

Nivolumab plus relatlimab, a PD-1/LAG-3 checkpoint pair, was evaluated in the phase I/IIa RELATIVITY-020 post-hoc brain-metastasis analysis (NCT01968109). Twenty-seven heavily pre-treated patients (100% prior anti-PD-1; 63% prior ipi/nivo; 81% prior brain RT) with measurable melanoma brain metastases received fixed-dose NIVO 480 mg + RELA 160 mg Q4W. Blinded central review using CNS-modified RECIST reported a 22% intracranial ORR (1 CR, 5 PR) and 63% clinical benefit (≥SD ≥6 mo) after a median 54.4-month follow-up. Median IC response duration and time to intracranial progression were not reached; 63% remained brain-progression-free >3 years. Median overall survival was 21.5 mo (70% at 1 year). Historical salvage options—re-challenging with ipilimumab or targeted radiotherapy—typically yield ≤10% IC responses and median OS ~9–12 mo in PD-1-refractory MBM.