Multicenter randomized phase 2 trial of ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma

The optimal therapeutic approach for metastatic melanoma with primary resistance to first-line PD-(L)1 blockade is not clear. The multicenter phase 2 SWOG S1616 trial in the USA randomized patients after progression on first-line PD-(L)1 blockade to receive the combination of ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) or ipilimumab alone. The progression-free survival was superior with the combination, as was the objective response rate (28% versus 9%; p=0.05). Grade 3 or higher treatment-related adverse events were reported for 57% of patients with the combination and 35% of patients with ipilimumab monotherapy, consistent with the known toxicity profiles of these regimens.The authors conclude that among patients with metastatic melanoma, primary resistance to PD-1 blockade can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade.