Pembrolizumab Combination Fails to Meet Primary Endpoint in Melanoma Study

The pivotal phase 3 ECHO-301/KEYNOTE-252 study evaluating Incyte’s epacadostat in combination with Merck’s pembrolizumab (Keytruda) in patients with unresectable or metastatic melanoma will be stopped after failing to meet its primary endpoint, according to a joint press release.

An external Data Monitoring Committee review of the phase 3 study determined that the study did not meet its primary endpoint of improving progression-free survival when compared with pembrolizumab monotherapy. The study’s second primary endpoint, overall survival, is not expected to reach statistical significance. The release also noted that the safety profile observed in the study was consistent with that observed in previously reported studies of epacadostat in combination with pembrolizumab.

The phase 3, randomized, double-blind, placebo-controlled study enrolled more than 700 patients, randomized 1:1 and stratified by tumor PD-L1 expression and BRAF mutation status. Key secondary endpoints included objective response rate, safety, and tolerability.

“While we are disappointed that this study did not confirm the efficacy of epacadostat in combination with Keytruda in patients with unresectable or metastatic melanoma, data from ECHO-301/KEYNOTE-252, including analyses of an extensive biomarker panel, will contribute to our understanding of the role of IDO1 inhibition in combination with PD-1 antagonists, and may inform our broader epacadostat clinical development program,” said Steven Stein, MD, chief medical officer of Incyte, in a statement.

According to STAT News, this was the first phase 3 trial to evaluate whether an IDO inhibitor in combination with a checkpoint inhibitor would allow more patients with cancer to benefit from immunotherapy treatment. However, study results showed no statistical difference between the combination and monotherapy.