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

Andrew S. BrohlEmail author,
Nikhil I. Khushalani,
Zeynep Eroglu,
Joseph Markowitz,
Ram Thapa,
Y. Ann Chen,
Ragini Kudchadkar and
Jeffrey S. Weber

Journal for ImmunoTherapy of Cancer20164:85

DOI: 10.1186/s40425-016-0194-1

Received: 28 September 2016

Accepted: 14 November 2016

Published: 20 December 2016

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.