Epacadostat in combination with Pembrolizumab in patients with unresectable or metastatic melanoma: ECHO-301/KEYNOTE-252 study stopped early for lack-of-benefit
An external Data Monitoring Committee ( eDMC ) review of the pivotal phase 3 ECHO-301/KEYNOTE-252 study results evaluating Epacadostat in combination with Pembrolizumab ( Keytruda ) in patients with unresectable or metastatic melanoma determined that the study did not meet the primary endpoint of improving progression-free survival in the overall population compared to Pembrolizumab monotherapy.
The study’s second primary endpoint of overall survival also is not expected to reach statistical significance.
Based on these results, and at the recommendation of the eDMC, the study will be stopped.
The safety profile observed in ECHO-301/KEYNOTE-252 was consistent with that observed in previously reported studies of Epacadostat in combination with Pembrolizumab.
This phase 3 randomized, double-blind, placebo-controlled study has evaluated Pembrolizumab in combination with Epacadostat or placebo in patients with unresectable or metastatic melanoma.
ECHO-301/KEYNOTE-252 enrolled over 700 patients, randomized 1:1, and stratified by tumor PD-L1 expression ( positive versus negative / indeterminate ) and BRAF mutation status ( BRAF mutant who have received prior BRAF-directed treatment, BRAF mutant with no prior BRAF-directed treatment and BRAF wild-type ).
The dual primary endpoints of the study are progression-free survival and overall survival. Key secondary endpoints include objective response rate, safety and tolerability.
The immunosuppressive effects of indoleamine 2,3-dioxygenase 1 ( IDO1 ) enzyme activity on the tumor microenvironment help cancer cells evade immunosurveillance.
Epacadostat is an investigational, highly potent and selective oral inhibitor of the IDO1 enzyme.
In clinical studies, the combination of Epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck and bladder cancer.
In these studies, Epacadostat combined with the CTLA-4 inhibitor Ipilimumab or the PD-1 inhibitors Pembrolizumab or Nivolumab improved response rates compared with studies of the immune checkpoint inhibitors alone.
Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. ( Xagena )
Source: Merck, 2018