Pembrolizumab ( Keytruda ) is a humanized monoclonal antibody against programmed death receptor-1 ( PD-1 ), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses.

Pembrolizumab, an intravenous drug, is indicated for the treatment of advanced ( unresectable or metastatic ) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial ( expansion cohorts ) and the phase II and III trials, KEYNOTE 002 and 006.
These studies were conducted in Ipilimumab-naïve and/or Ipilimumab-experienced patients and assessed varying Pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks.

In the trials with active comparator arms, Pembrolizumab regimens significantly improved progression-free survival ( PFS ), overall survival ( OS ) and overall response rates ( ORR ) relative to Ipilimumab in Ipilimumab-naïve patients ( KEYNOTE 006 ), and significantly improved progression-free survival and overall response rates, but not overall survival ( although overall survival data are immature ), relative to chemotherapy in Ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive ( KEYNOTE 002 ).

Pembrolizumab has an acceptable tolerability profile, with immune-related adverse events that are generally manageable / reversible. Thus, pembrolizumab is a valuable treatment option for patients with advanced melanoma, including those who have progressed on Ipilimumab and BRAF/MEK inhibitors. ( Xagena )

Deeks ED, Drugs 2016;76: 375-386