BACKGROUND: The programmed death 1 (PD-1) receptor is a negative regulator of 
T-cell effector mechanisms that limits immune responses against cancer. We 
tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in 
patients with advanced melanoma.
METHODS: We administered lambrolizumab intravenously at a dose of 10 mg per 
kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in 
patients with advanced melanoma, both those who had received prior treatment 
with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor 
responses were assessed every 12 weeks.
RESULTS: A total of 135 patients with advanced melanoma were treated. Common 
adverse events attributed to treatment were fatigue, rash, pruritus, and 
diarrhea; most of the adverse events were low grade. The confirmed response rate 
across all dose cohorts, evaluated by central radiologic review according to the 
Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% 
confidence interval [CI], 25 to 44), with the highest confirmed response rate 
observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% 
CI, 38 to 66). The response rate did not differ significantly between patients 
who had received prior ipilimumab treatment and those who had not (confirmed 
response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). 
Responses were durable in the majority of patients (median follow-up, 11 months 
among patients who had a response); 81% of the patients who had a response (42 
of 52) were still receiving treatment at the time of analysis in March 2013. The 
overall median progression-free survival among the 135 patients was longer than 
7 months.
CONCLUSIONS: In patients with advanced melanoma, including those who had had 
disease progression while they had been receiving ipilimumab, treatment with 
lambrolizumab resulted in a high rate of sustained tumor regression, with mainly 
grade 1 or 2 toxic effects. (Funded by Merck Sharp and Dohme; ClinicalTrials.gov 
number, NCT01295827.).