Annual Review of Cancer Biology, volume 4, issue 1, pages 241-256

Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?

Benoit J. Van den Eynde 1, 2, 3
Nicolas van Baren 2
Jean-François Baurain 4, 5
1
 
Ludwig Institute for Cancer Research, Brussels B-1200, Belgium;
3
 
Walloon Excellence in Life Sciences and Biotechnology, Brussels B-1200, Belgium
4
 
King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Brussels B-1200, Belgium
Publication typeJournal Article
Publication date2020-03-09
scimago Q1
wos Q1
SJR3.766
CiteScore14.5
Impact factor4.7
ISSN24723428
Cancer Research
Oncology
Cell Biology
Abstract

Indoleamine-2,3 dioxygenase 1 (IDO1) contributes to tumor immunosuppression by enzymatically degrading tryptophan, which is required for T cell activity, and producing kynurenine. Small-molecule inhibitors, such as epacadostat, have been developed to block IDO1 activity. In preclinical models, they can restore antitumoral T cell immunity and synergize with immune checkpoint inhibitors or cancer vaccines. Based on encouraging clinical results in early phase trials, a randomized phase III study (ECHO-301/KN-252) was launched in metastatic melanoma to test the benefit of adding epacadostat to the reference pembrolizumab therapy. The result was negative. We briefly review the clinical trials that investigated epacadostat in cancer patients and discuss possible explanations for this negative result. We end by suggesting paths to resume clinical development of compounds targeting the IDO1 pathway, which in our view remains an attractive target for cancer immunotherapy.

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