# Epacadostat

Source: https://onco.cc/drugs/epacadostat/  
OnCo record `epacadostat` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Treatment
- Status: negative
- Last checked: 2026-09-06
- Tags: failure; lesson:phase-2-mirage
- Code: INCB024360
- Modality: Small molecule (IDO1 inhibitor)
- Mechanism: Selective, reversible IDO1 enzyme inhibitor.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Epacadostat
- ECHO-301/KEYNOTE-252 (Lancet Oncol 2019): https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30274-8/fulltext

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [IDO1](https://onco.cc/targets/ido1/), [TDO2](https://onco.cc/targets/tdo2/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Incyte](https://onco.cc/companies/incyte/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- trials: [Epacadostat (INCB024360) Added to Preoperative Chemoradiation in Patients With Locally Advanced Rectal Cancer](https://onco.cc/trials/nct03516708/), [Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer](https://onco.cc/trials/nct03348904/), [Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)](https://onco.cc/trials/nct03260894/), [Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)](https://onco.cc/trials/nct03358472/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/)
- ideas: [No accelerated approval for a combination without proof each part contributes](https://onco.cc/ideas/idea-tr2-contribution-of-components-mandate/), [Public post-mortem reports when a cancer drug programme is stopped](https://onco.cc/ideas/idea-tr2-termination-reports/)
- pathways: [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/)

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