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Background: Programmed death-1(PD-1)is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity.Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1.This study explored the safety and clinical activity of lambrolizumab in patients(pts)with advanced melanoma(MEL).Methods: In this ongoing phase 1b expansion study of MEL pts with or without previous ipilimumab(IPI)treatment,lambrolizumab was administered Ⅳ every 2 or 3 weeks until disease progression or unacceptable toxicity.Tumor response was assessed every 12 weeks by independent,central,blinded radiographic review per immune-related response criteria and RECIST 1.1.Results: As of December 1,2012,294 pts with MEL were enrolled,including 179 IPI-naive and 115 IPI-pretreated.Pts received lambrolizumab 10 mg/kg(n = 183)or 2 mg/kg(n = 111).Preliminary data from the first 85 consecutive pts dosed before April 25,2012,who had independent radiologic review available as of December 3,2012,indicate a confirmed overall response rate per RECIST 1.1 of greater than 35%,pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients.The median duration of response has not been reached as only 2 pts who had initial response discontinued due to disease progression,but the duration of confirmed responses range from 28+ to 240+ days(up to 8+ months).Among 133 pts who were dosed with lambrolizumab before July 31,2012,and evaluable for adverse events(AEs)as of September 28,2012,fatigue(22%),rash(18%),and pruritus(14%)were the most common drug-related AEs(mostly grade 1/2).The incidence of drug-related grade 3/4 AEs was 10%(24%regardless of attribution).Four drug-related cases of pneumonitis were reported,all of grade 1/2.Grade 3/4 drug-related hypothyroidism(n = 1)and hyperthyroidism(n = 1)were noted.Conclusions: Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated MEL pts.These data have led to an ongoing,international,randomized study of lambrolizumab versus chemotherapy in IPI-pretreated MEL.