Spartalizumab (PD-1) + Dabrafenib/Trametinib Extends OS vs BRAF/MEK Alone in BRAF V600 Melanoma

Spartalizumab is an anti–PD-1 monoclonal antibody combined here with dabrafenib (BRAF inhibitor) plus trametinib (MEK inhibitor) as first-line targeted therapy intensification for BRAF V600-mutant unresectable/metastatic melanoma in the randomized Phase 3 COMBI-I trial (NCT02967692). With ≥5 years’ follow-up (median 76.9 months), median OS was 61.5 months with sparta-DabTram (n=267) vs 41.6 months with placebo-DabTram (n=265) (HR 0.760, 95% CI 0.598–0.966), despite the study missing its primary endpoint (PFS at 24 months); for context, historical pooled COMBI-d/COMBI-v dabrafenib+trametinib reported mOS 25.9 months (5-year OS 34%). Pyrexia was the most common TRAE (65.9% vs 46.2%), and grade ≥3 TRAEs were higher with spartalizumab triplet therapy (57.3% vs 36.7%), without new safety signals.