Adjuvant anti-TIGIT plus anti-PD-1 in melanoma: A necessary failure that clarifies the path forward

The phase 3 KEYVIBE-010 trial investigated adjuvant vibostolimab (anti-TIGIT) plus pembrolizumab versus pembrolizumab alone in resected stage IIB-IV melanoma. At the first interim analysis, the combination met futility criteria, with a recurrence-free survival hazard ratio of 1.25 (95% CI 0.9-1.8), indicating worse outcomes. Serious adverse events (11%vs. 4%) and grade ≥3 immune-mediated events (12%vs. 4%) were higher with the combination, including two treatment-related deaths in the combination arm and one in the pembrolizumab arm. Despite promising early-phase signals, this rigorous, double-blind, active-comparator trial confirms that adding TIGIT blockade does not improve efficacy and increases toxicity. Pembrolizumab monotherapy remains a standard-of-care option in the adjuvant setting, though other established regimens (e.g., nivolumab, dabrafenib/trametinib) apply to specific subgroups. The trial highlights the need for active comparators, futility boundaries, and predictive biomarkers in future adjuvant immunotherapy studies.