Anti–PD-1 Antibody Pembrolizumab Shows Activity and Good Tolerability in Ipilimumab-Refractory Advanced Melanoma
As reported in The Lancet by Robert et al, the anti–programmed death receptor-1 (PD-1) antibody pembrolizumab produced responses and was well tolerated at two dose levels in an expansion cohort of a phase I trial in patients with ipilimumab (Yervoy)-refractory advanced melanoma.
In this open-label multicenter trial, 173 adult patients with advanced melanoma progressing after at least two ipilimumab doses were randomly assigned to receive intravenous pembrolizumab at 2 mg/kg (n = 89) or 10 mg/kg (n = 84) every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was overall response rate on independent central review.
Response Rates
Median follow-up was 8 months. Objective response occurred in 21 (26%) of 81 patients in the 2 mg/kg group and 20 (26%) of 76 in the 10 mg/kg group (difference = 0%, 95% confidence interval = −14 to 13, P = .96).
Toxicity
Treatment was well tolerated, and safety profiles were similar at the two dose levels. The most common drug-related adverse events of any grade were fatigue, which occurred in 33% of the 2 mg/kg group and 37% of the 10 mg/kg group, pruritus (26% and 19%), and rash (18% and 18%).
The only drug-related grade 3 or 4 adverse event reported in more than one patient was grade 3 fatigue, which occurred in 3% of patients in the 2 mg/kg group. There were no drug-related deaths.
The investigators concluded, “The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options.”
Caroline Robert, MD, of Institut Gustave Roussy, is the corresponding author for The Lancet article.
The study was funded by Merck Sharp and Dohme. For full disclosures of the study authors, visit www.thelancet.com.
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