A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma

• Type of Material: Article
• Authors: Andrew S. Brohl, H. Lee Moffitt Cancer Center and Research Institute; Nikhil I. Khushalani, H. Lee Moffitt Cancer Center and Research Institute; Zeynep Eroglu, H. Lee Moffitt Cancer Center and Research Institute; Joseph Markowitz, H. Lee Moffitt Cancer Center and Research Institute; Ram Thapa, H. Lee Moffitt Cancer Center and Research Institute; Y. Ann Chen, H. Lee Moffitt Cancer Center and Research Institute; Ragini Kudchadkar, Emory University; Jeffrey S. Weber, H. Lee Moffitt Cancer Center and Research Institute
• Language: English
• Date: 2016-05-20
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2016
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s40425-016-0194-1
• Title of Journal or Parent Work: Journal for ImmunoTherapy of Cancer
• ISSN: 2051-1426
• Volume: 4
• Issue: 85
• Start Page: 85
• End Page: 85
• Grant/Funding Information: Merck & Co.
• Keywords: Life Sciences & Biomedicine; Oncology; Science & Technology; ONCOLOGY
• Research Categories: Biology, Bioinformatics; Health Sciences, Oncology; Health Sciences, General

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 12weeks. 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 3mg/kg dosing with peginterfeon alfa-2b at 2μg/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 5.9months. The median overall survival was not reached with at a median follow-up of 35.8months. Conclusions: We report that the combination of ipilimumab at 3mg/kg dosing combined with peginterfeon alfa-2b at 2μg/kg/week demonstrated an acceptable toxicity profile and a promising efficacy signal. Further study of this combination is warranted. Trial registration: ClinicalTrials.gov identifier: NCT01496807, Registered December 19th, 2011.