Davar D, et al. - In this phase Ib/II study in patients with programmed death-1 (PD-1)-naïve advanced melanoma, researchers assessed pembrolizumab/pegylated (PEG)-interferon (IFN) combination, focusing mainly on safety and incidence of dose-limiting toxicities. An acceptable toxicity profile was displayed by pembrolizumab/PEG-IFN and strong evidence of clinical efficacy in PD-1–naïve metastatic melanoma.

Methods

• Using a modified toxicity probability interval design, PEG-IFN (1, 2, and 3 μg/kg per week) was dose escalated in three cohorts of four patients each.
• Researchers dosed pembrolizumab at 2 mg/kg every 3 weeks in the phase Ib portion; the phase II portion included 31 patients.
• Safety and incidence of dose-limiting toxicities were mainly assessed (primary objectives), additionally, objective response rate, progression-free survival (PFS), and overall survival were evaluated (secondary objectives).

Results

• The phase Ib and II portions of the study, as well as the analysis included a total of 43 patients with stage IV melanoma.
• Median follow-up duration was 25 months (range, 1 to 38 months), at the data cutoff date (December 31, 2017).
• At least one adverse event occurred in all 43 patients; the occurrence of grade 3/4 treatment-related adverse events was reported in 21 of 43 patients (48.8%).
• At all three dose levels, objective responses were seen among 43 evaluable patients.
• The estimated objective response rate was 60.5%; ongoing response was seen in 46.5% of patients.
• A median PFS of 11.0 months was seen in all patients and PFS remained unreached in responders, whereas, in all patients, median overall survival remained unreached.
• The estimated 2-year PFS rate was 46%.