title: A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma.
abstract: BACKGROUND
  Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination.
  
  
  METHODS
  Study treatment consisted of ipilimumab given every 3 weeks, for a total of four infusions, concurrent with peginterferon alfa-2b administered subcutaneous weekly for a total of 12 weeks. This was followed by maintenance therapy with peginterferon alfa-2b administered subcutaneously weekly for up to 144 additional weeks. The study was designed as a two-stage dose escalation scheme with continuous dose-limiting toxicity monitoring during the induction phase.
  
  
  RESULTS
  Thirty one patients received at least 1 dose of study treatment and 30 were assessable for efficacy endpoints. We found that ipilimumab at 3 mg/kg dosing with peginterfeon alfa-2b at 2 μg/kg/week was the maximum tolerated dose of this combination. The incidence of grade 3 drug-related adverse events (AEs) was 45.2%. There were no grade 4/5 AEs. The overall response rate was 40% by immune-related response criteria. Median progression-free survival was 5.9 months. The median overall survival was not reached with at a median follow-up of 35.8 months.
  
  
  CONCLUSIONS
  We report that the combination of ipilimumab at 3 mg/kg dosing combined with peginterfeon alfa-2b at 2 μg/kg/week demonstrated an acceptable toxicity profile and a promising efficacy signal. Further study of this combination is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01496807, Registered December 19th, 2011.
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brohl
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA.
authors.forename: Nikhil I
authors.initials: NI
authors.lastname: Khushalani
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Thapa
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors.forename: Y Ann
authors.initials: YA
authors.lastname: Chen
authors.affiliation: Winship Cancer Institute of Emory University, Atlanta, GA USA.
authors.forename: Ragini
authors.initials: R
authors.lastname: Kudchadkar
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA ; New York University Langone Medical Center, New York, NY USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
keywords: Clinical trial; Immunotherapy; Ipilimumab; Melanoma; Peginterferon alfa-2b