Melanoma Coverage from Every Angle

Epacadostat With Pembrolizumab in Advanced Melanoma

By: Melissa E. Fryman, MS
Posted: Thursday, August 15, 2019

Epacadostat with pembrolizumab appears to be no better than pembrolizumab alone in the treatment of patients with unresectable or metastatic melanoma, according to a report by Georgina V. Long, PhD, of the Melanoma Institute Australia, University of Sydney, and colleagues. The indoleamine 2,3-dioxygenase-1 inhibitor had shown promise in a prior phase I/II trial, as well as preclinical trials, when combined with anti–PD-1/L1 immunotherapy, but not as monotherapy. These phase III findings from ECHO-301/KEYNOTE-252 were published in The Lancet Oncology.  

In this international, double-blinded study, 706 patients with unresectable, stage III or IV melanoma were randomly assigned to receive pembrolizumab with 100 mg of epacadostat twice daily, or placebo. All study patients had not previously received checkpoint inhibitor therapy.

After a median follow-up of 12.4 months, no differences in median progression-free survival (4.7 vs. 4.9 months for combination therapy or pembrolizumab alone), overall survival (not reached), or objective response were observed between the study groups. Due to these findings, the study was stopped after completion of the second interim analyses. Analyses of pharmacokinetics, pharmacodynamics, antipembrolizumab antibodies, and quality of life were not completed.

The combination treatment was generally well tolerated, and treatment-related adverse events were similar in both groups. Increase in lipase was the most common grade 3 or worse adverse event.

“To our knowledge, this was the first large randomized study across the field of immuno-oncology showing no further benefit from the addition of an immune agent other than anti–CTLA-4 to anti–PD-1 checkpoint inhibition,” the authors concluded. “Overall, these results illustrate the challenge of proceeding to phase III assessment of a promising immunotherapy agent without evidence from a randomized phase II study.”

Disclosure: The study authors’ disclosure information may be found at

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