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First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies
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Abstract Purpose: Indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the degradation of tryptophan to N-formyl-kynurenine. Overexpressed in many solid malignancies, IDO1 can promote tumor escape from host immunosurveillance. This first-in-human phase I study investigated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of epacadostat (INCB024360), a potent and selective inhibitor of IDO1. Experimental Design: Fifty-two patients with advanced solid malignancies were treated with epacadostat [50 mg once daily or 50, 100, 300, 400, 500, 600, or 700 mg twice daily (BID)] in a dose-escalation 3 + 3 design and evaluated in 28-day cycles. Treatment was continued until disease progression or unacceptable toxicity. Results: One dose-limiting toxicity (DLT) occurred at the dose of 300 mg BID (grade 3, radiation pneumonitis); another DLT occurred at 400 mg BID (grade 3, fatigue). The most common adverse events in >20% of patients overall were fatigue, nausea, decreased appetite, vomiting, constipation, abdominal pain, diarrhea, dyspnea, back pain, and cough. Treatment produced significant dose-dependent reductions in plasma kynurenine levels and in the plasma kynurenine/tryptophan ratio at all doses and in all patients. Near maximal changes were observed at doses of ≥100 mg BID with >80% to 90% inhibition of IDO1 achieved throughout the dosing period. Although no objective responses were detected, stable disease lasting ≥16 weeks was observed in 7 of 52 patients. Conclusions: Epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. Clin Cancer Res; 23(13); 3269–76. ©2017 AACR.
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“Regarding dosing of epacadostat, 100 mg was taken forward out of the phase I study despite higher dose levels being tolerable and no maximum tolerated dose being established (59).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [59]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationPD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Nivolumab in Previously Untreated Melanoma without BRAF Mutation
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., Hassel, J. C., Rutkowski, P., McNeil, C., Kalinka-Warzocha, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412082 · Cited by 5,519
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496
Innate and adaptive immune cells in the tumor microenvironment
Gajewski, T. F., Schreiber, H., & Fu, Y.-X. (2013) · Nature Immunology · doi:10.1038/ni.2703 · Cited by 4,148
Self-citationPrevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I. E., Conway, S. J., Marshall, B., Brown, C. C., & Mellor, A. L. (1998) · Science · doi:10.1126/science.281.5380.1191 · Cited by 2,589
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305
Research works printed but not linked: 1
- Gangadhar, 2016, Epacadostat plus pembrolizumab in patients with advanced melanoma and select solid tumors: Updated phase 1 results from ECHO-202/KEYNOTE-037, Ann Oncol, 27, vi381, 10.1093/annonc/mdw379.06 · DOI
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Togashi, Y., Shitara, K., & Nishikawa, H. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0175-7 · Cited by 1,620
Natural killer cells and other innate lymphoid cells in cancer
Chiossone, L., Dumas, P., Vienne, M., & Vivier, É. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0061-z · Cited by 1,034
Long, G. V., Dummer, R., Hamid, O., Gajewski, T. F., Caglevic, C., Dalle, S., Arance, A., Carlino, M. S., Grob, J.-J., Kim, T. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30274-8 · Cited by 960
Self-citationNext generation of immune checkpoint therapy in cancer: new developments and challenges
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Metadata
- Authors
- Beatty, G. L., O'Dwyer, P. J., Clark, J., Shi, J. G., Bowman, K. J., Scherle, P. A., Newton, R. C., Schaub, R., Maleski, J., Leopold, L., & Gajewski, T. F.
- Affiliations
- Abramson Cancer Center (US)
- Incyte (United States) (US)
- University of Chicago (US)
- Corresponding author
- Beatty, Gregory L.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2017-07-01
- Volume
- 23
- Issue
- 13
- Pages
- 3269-3276
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC5496788
- OpenAlex
- W2570766240
- Cited by
- 314
- References
- 40
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 42 · 2023: 21 · 2022: 26 · 2021: 36 · 2020: 33 · 2019: 44 · 2018: 53 · 2017: 24
- FWCI
- 18.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Chicago
- Abramson Cancer Center
- National Cancer Institute (K08CA138907)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- epacadostat, IDO1, IDO1 inhibitors, advanced solid tumors, kynurenine, kynurenine/tryptophan ratio, tryptophan degradation, tumor immunosuppression, radiation pneumonitis, dose-limiting toxicity, pharmacokinetics, pharmacodynamics, anticancer activity, maximum tolerated dose
- MeSH terms
- Administration, Oral, Adult, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Neoplasm Staging, Neoplasms, Oximes, Sulfonamides, Indoleamine-Pyrrole 2,3,-Dioxygenase, Drug-Related Side Effects and Adverse Reactions
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