title: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
abstract: 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.).
authors.affiliation: Angeles Clinic and Research Institute, Los Angeles, CA, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Roxana
authors.initials: R
authors.lastname: Dronca
authors.forename: Tara C
authors.initials: TC
authors.lastname: Gangadhar
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
authors.forename: Hassane
authors.initials: H
authors.lastname: Zarour
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.forename: Kevin
authors.initials: K
authors.lastname: Gergich
authors.forename: Jeroen
authors.initials: J
authors.lastname: Elassaiss-Schaap
authors.forename: Alain
authors.initials: A
authors.lastname: Algazi
authors.forename: Christine
authors.initials: C
authors.lastname: Mateus
authors.forename: Peter
authors.initials: P
authors.lastname: Boasberg
authors.forename: Paul C
authors.initials: PC
authors.lastname: Tumeh
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: Scot W
authors.initials: SW
authors.lastname: Ebbinghaus
authors.forename: Xiaoyun Nicole
authors.initials: XN
authors.lastname: Li
authors.forename: S Peter
authors.initials: SP
authors.lastname: Kang
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab