Epacadostat
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| Formula | C11H13BrFN7O4S |
| Molar mass | 438.23 g·mol−1 |
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Epacadostat (previously INCB24360) is an investigational drug for cancer.[1] Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).[1][2][3] Epacadostat inhibits IDO1 by competitively blocking it, without interfering with IDO2 or tryptophan 2,3-dioxygenase (TDO). It has antitumor activity in some models, though is most effective when combined with other immunotherapy agents.[4]
History and clinical trials
[edit]As of 2017, the combination of epacadostat with pembrolizumab (Keytruda) was being investigated by Incyte and Merck & Co. in several cancers, as was the combination of epacadostat with nivolumab (Opdivo) by Incyte and Bristol Myers Squibb.[5]
In April 2018, Incyte announced they were halting the Phase III ECHO-301/KEYNOTE-252 (NCT02752074) trial of epacadostat with pembrolizumab for melanoma as the combination therapy missed the first primary endpoint of improving progression-free survival vs. pembrolizumab alone.[6][7] The second primary endpoint of overall survival is not yet determined.[6]
References
[edit]- ^ a b "Epacadostat". NCI Drug Dictionary. National Cancer Institute. 2011-02-02.
- ^ Brochez L, Chevolet I, Kruse V (May 2017). "The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy". European Journal of Cancer. 76: 167–182. doi:10.1016/j.ejca.2017.01.011. PMID 28324751.
- ^ Yue EW, Sparks R, Polam P, Modi D, Douty B, Wayland B, et al. (May 2017). "INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology". ACS Medicinal Chemistry Letters. 8 (5): 486–491. doi:10.1021/acsmedchemlett.6b00391. PMC 5430407. PMID 28523098.
- ^ Van den Eynde BJ, van Baren N, Baurain JF (2020). "Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?". Annual Review of Cancer Biology. 4: 241–256. doi:10.1146/annurev-cancerbio-030419-033635.
- ^ Staton T (3 April 2017). "Racing in lung cancer again (or still), Merck and BMS expand Incyte combo trials". FiercePharma.
- ^ a b "Incyte, Merck & Co. Halt Phase III Trial After Epacadostat/Keytruda Combination Fails in Melanoma". 6 April 2018.
- ^ Walters J (6 April 2018). "Incyte Tumbles After Epacadostat Miss". BioCentury.