Safety profile of nivolumab (NIVO) in patients (pts) with advanced melanoma (MEL): A pooled analysis.

9018 Background: NIVO is a programmed death-1 (PD-1) immune checkpoint inhibitor which has shown durable tumor responses in multiple cancer types and prolongs overall survival in pts with MEL. The objective of the current analysis is to describe the safety profile of NIVO across recent MEL studies, including 4 studies in which guidelines for the management of adverse events (AEs) were utilized. Methods: A retrospective safety review was conducted for 4 ongoing phase I–III trials, in which MEL pts received NIVO 3 mg/kg Q2W until disease progression or unacceptable toxicity. Data were included from pts who received at least 1 dose of NIVO, and included assessments of AEs, select AEs (immune-related etiology), time to onset and resolution, and the use as well as impact of immune modulating agents (IMs). Results: A total of 576 patients received NIVO for a median of 3.7 months; 312 (54%) had received prior ipilimumab (IPI). The most frequent drug-related AEs of any grade were fatigue (25%), pruritus (17%), diarrhea (13%), and rash (13%); grade 3–4 drug-related AEs occurred in 10% of all pts, and in 8% of pts with prior IPI. No drug-related deaths were reported. Drug-related select AEs of any grade were most frequent in the skin (34%), GI tract (13%), endocrine glands (8%) and liver (4%); grade 3–4 select AEs occurred in 4% of pts. Median time to onset of drug-related select AEs ranged from 5 wks for skin AEs to 15 wks for renal AEs. IMs were administered to 166/474 pts (35%) in phase III studies to manage AEs; 114 pts (24%) received systemic corticosteroids. Among 21 pts with grade 3–4 drug-related select AEs, all but 1 pt with a skin AE resolved with IMs. Median time to resolution ranged from 3 wks for hepatic AEs to 29 wks for skin AEs. The objective response rate was 44% in pts who received an IM and 36% in those who did not; time to response was similar (median 9 wks), and the median duration of response was not reached for either pt subgroup. Conclusions: In this pooled analysis, drug-related AEs with NIVO monotherapy were primarily low grade and the incidence of grade 3–4 drug-related AEs was not affected by prior IPI. Nearly all drug-related grade 3–4 select AEs resolved with use of IMs, which did not appear to impact on tumor response.