Multinational nonrandomized phase 1-2 study of nivolumab with or without ipilimumab for recurrent or metastatic Merkel cell carcinoma

Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistence to PD-(L)1 blockade, which may be overcome using combination immune checkpoint blockade (ICI) with anti-CTLA-4 antibody. In the recurrent/metastatic (R/M) MCC cohort of the multinational nonrandomized phase 1-2 CheckMate 358 trial, ICI-naïve patients with 0-2 previous line of systemic therapy received nivolumab monotherapy or nivolumab plus ipilmumab. The objective response rates were 60% with nivolumab monotherapy and 58% with the combination, with median duration of response 60.6 months and 25.9 months, respectively. Median progression-free survival and overall survival were 21.3 months and 80.7 months, respectively, with nivolumab monotherapy and 8.4 months and 29.8 months, respectively, with the combination. The incidence of grade 3 or 4 treatment-related adverse events was 28% with nivolumab monotherapy and 47% with the combination . The authors conclude that this nonrandomized study showed frequent and durable responses with both nivolumab and nivolumab plus ipilimumab in patients with ICI-naïve advanced MCC. However, it did not show improvement in efficacy with the combination over nivolumab monotherapy.