{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:01:44Z","timestamp":1791615704156,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T00:00:00Z","timestamp":1667088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017655","name":"Incyte Corp","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Targeting programmed cell death protein 1 (PD\u20101) and indoleamine 2,3\u2010dioxygenase (IDO1) pathways is an appealing option for cancer treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The open\u2010label, phase 1\/2 ECHO\u2010203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti\u2013PD\u2010L1 monoclonal antibody in adult patients with advanced solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The most common treatment\u2010related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)\u2010na\u00efve patients (16.1%) compared with patients who had received previous CPI (4.1%). Epacadostat pharmacodynamics were evaluated by comparing baseline kynurenine levels with those on therapy at various time points. Only the 300\u2010mg epacadostat dose showed evidence of kynurenine modulation, albeit unsustained.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Epacadostat plus durvalumab was generally well tolerated in patients with advanced solid tumors. ORR was low, and evaluation of kynurenine concentration from baseline to cycle 2,\u00a0day 1, and cycle 5,\u00a0day 1, suggested &gt;300\u00a0mg epacadostat twice daily is needed to ensure sufficient drug effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial information<\/jats:title><jats:p>A study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO\u2010203) (NCT02318277).<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34512","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T04:43:19Z","timestamp":1667104999000},"page":"71-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Phase 1\/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-8513","authenticated-orcid":false,"given":"Aung","family":"Naing","sequence":"first","affiliation":[{"name":"MD Anderson Cancer Center University of Texas  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain P.","family":"Algazi","sequence":"additional","affiliation":[{"name":"University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Falchook","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Creelan","sequence":"additional","affiliation":[{"name":"Moffit Cancer Center  Tampa Florida 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