{"entity":{"id":"epacadostat","kind":"drug","name":"Epacadostat","aka":[],"tldr":"An enzyme blocker meant to stop tumours starving T cells of tryptophan. Its 2018 phase 3 failure ended an entire class overnight.","summary":"IDO1 degrades tryptophan to kynurenine, suppressing T cells. Epacadostat plus pembrolizumab produced ~55% response rates in a phase 1/2 melanoma cohort. ECHO-301/KEYNOTE-252 (n=706, first-line melanoma) showed no PFS or OS difference (2018). Incyte, Merck, BMS, and others halted more than a dozen IDO1 trials within weeks; the drug may never have achieved adequate pathway inhibition in tumours.\n\nLesson: pharmacodynamic proof of target engagement in the tumour should precede phase 3; a large uncontrolled response rate on a pembrolizumab backbone in melanoma is not evidence of added benefit.","status":"negative","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Epacadostat","links":[{"label":"ECHO-301/KEYNOTE-252 (Lancet Oncol 2019)","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30274-8/fulltext"}],"tags":["failure","lesson:phase-2-mirage"],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ido1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03260894","nct03358472","nct03348904"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"INCB024360","modality":"Small molecule (IDO1 inhibitor)","mechanism":"Selective, reversible IDO1 enzyme inhibitor.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/epacadostat/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"ido1","kind":"target","name":"IDO1","route":"/targets/ido1/"},{"id":"tdo2","kind":"target","name":"TDO2","route":"/targets/tdo2/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"incyte","kind":"company","name":"Incyte","route":"/companies/incyte/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"trial":[{"id":"nct03516708","kind":"trial","name":"Epacadostat (INCB024360) Added to Preoperative Chemoradiation in Patients With Locally Advanced Rectal Cancer","route":"/trials/nct03516708/"},{"id":"nct03348904","kind":"trial","name":"Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer","route":"/trials/nct03348904/"},{"id":"nct03260894","kind":"trial","name":"Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)","route":"/trials/nct03260894/"},{"id":"nct03358472","kind":"trial","name":"Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)","route":"/trials/nct03358472/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"idea":[{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","route":"/ideas/idea-tr2-contribution-of-components-mandate/"},{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","route":"/ideas/idea-tr2-termination-reports/"}],"pathway":[{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"}]}}