Epacadostat
An enzyme blocker meant to stop tumours starving T cells of tryptophan. Its 2018 phase 3 failure ended an entire class overnight.
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.
Lesson: 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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Latest papers
topQuery for this drug: (TITLE:"Epacadostat" OR ABSTRACT:"Epacadostat" OR TITLE:"INCB024360" OR ABSTRACT:"INCB024360") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Epacadostat, not a curated reading list.
Pages like this
not linked directly; found by shared links- ProductTiragolumab
Shares No accelerated approval for a combination without proof each part contributes, Failures are hidden, Cold tumours and the immunosuppressive microenvironment, Immune checkpoint inhibitors and the tags failure, lesson:phase-2-mirage.
- ProductBempegaldesleukin
Shares Failures are hidden, Melanoma and the tags failure, lesson:phase-2-mirage.
- ProductRovalpituzumab tesirine
Shares Public post-mortem reports when a cancer drug programme is stopped, Failures are hidden and the tag failure.
- ProductMagrolimab
Shares Public post-mortem reports when a cancer drug programme is stopped, Failures are hidden, Cold tumours and the immunosuppressive microenvironment and the tag failure.
- TrialIMpassion131
Shares No accelerated approval for a combination without proof each part contributes, Pembrolizumab and the tag failure.
- ProductADU-S100 (MIW815)
Shares Cold tumours and the immunosuppressive microenvironment, Melanoma and the tag failure.
- TrialFianlimab + cemiplimab phase 3 (first-line melanoma)
Shares Pembrolizumab, Melanoma and the tag failure.
- ProductMelphalan flufenamide
Shares Failures are hidden and the tag failure.