Safety of reduced infusion times for nivolumab plus ipilimumab (N + I) and nivolumab alone (N) in advanced melanoma

Abstract

Background: The phase 3 melanoma (MEL) study CheckMate 067 showed improved progression-free survival and objective response rates with N + I or N versus ipilimumab monotherapy, with treatment-related grade 3/4 adverse events (AEs) reported in 55%, 16%, and 27% of patients ( pts), respectively. The objective of this analysis was to assess the safety profile associated with reduced infusion times for N + I (from 180 to 90 min) and N (from 60 to 30 min) using data from a phase 1 biomarker study (CA209-038). Methods: The primary objective of the study was to assess the pharmacodynamic activity of N + I and N on the tumor microenvironment. Exploratory objectives included assessment of safety, tolerability, and pharmacokinetics of reduced infusion times for N + I and N. Pts with previously treated or untreated MEL were divided into 4 non-randomized groups with different follow-up times: N + I (1 mg/kg + 3 mg/kg Q3W for 4 doses then N 3 mg/kg Q2W for either 180 min [N + I 180 group, n = 27] or 90 min [N + I 90 group, n = 36]) or N (3 mg/kg Q2W for either 60 min [N 60 group, n = 85] or 30 min [N 30 group, n = 20]). Pts were treated for up to 2 years or until confirmed disease progression or intolerable toxicity. Results: Across the 4 study groups (n = 168), the majority of pts did not experience an infusion (97%) or hypersensitivity (96%) reaction. 5 (3%) pts had any grade infusion reaction and 3 (2%) experienced any grade hypersensitivity; no grade 3/4 infusion or hypersensitivity reactions were reported. In the N + I 180 and N + I 90 groups, 4% and 8% of pts, respectively, had 1 or more infusion interruptions; in the N 60 and N 30 groups, the rate was 14% and 5%, respectively. The rate of treatment-related grade 3/4 AEs for N + I 180, N + I 90, N 60, and N 30 groups was 52%, 31%, 5%, and 0%, respectively. Conclusions: Reducing the infusion times for N + I (from 180 to 90 min) and N (from 60 to 30 min) resulted in similar low levels of infusion reactions, suggesting that this approach may speed up treatment administration for pts and treatment centers. Additional data on safety, pharmacokinetics and response rates will be presented.