Table 5.

Profile of representative clinical trials of epacadostat

Treatment	Identifier/Trial name	Phase	Patients	Key results	Ref
Epacadostat	NCT01195311	I	52	1. MTD not established with dosing up to 700 mg BID 2. Near maximal changes observed at doses of ≥ 100 mg BID with > 80–90 % IDO1 inhibition achieved 3. Stable disease lasting ≥ 16 weeks observed in 7 patients 4. 300 mg BID selected as the recommended phase II monotherapy dose 5. PD modelling established	[91, 92]
Epacadostat	NCT01685255	I/II	42	1. Trial terminated due to slow accrual and lack of evidence of superiority 2. No significant difference in efficacy observed compared to tamoxifen in biochemical-only relapse ovarian cancer 3. IDO1 expression observed in 94 % of archival tumor samples	[94]
Epacadostat + ipilimumab	NCT01604889	I/II	50	1. Doses ≤ 50 mg BID generally well tolerated when combined with ipilimumab 2. IDO1 inhibition achieved with epacadostat doses ≥ 25 mg BID	[95]a
Epacadostat + pembrolizumab	NCT02178722 ECHO-202/ KEYNOTE-037	I/II	62	1. 100 mg BID plus pembrolizumab recommended for phase II evaluation 2. 12 (55 %) of 22 patients with melanoma achieved objective response	[76]b
Epacadostat + nivolumab	NCT02327078 ECHO-204	I/II	50	1. 100 mg BID plus nivolumab recommended for phase III evaluation 2. 31 (62 %) of 50 patients with melanoma achieved objective disease	[77]c
Epacadostat + pembrolizumab	NCT02752074 ECHO-301/KEYNOTE-252	III	706	1. No significant difference in PFS found between the treatment groups (median 4.7 months for epacadostat plus pembrolizumab vs. 4.9 months for pembrolizumab alone; [HR] 1.00; one-sided p = 0.52) 2. No significant difference in PFS found between the treatment groups in IDO1-positive patient	[78]

^a The trial was originally designed as a phase I/II trial and later suspended further patient enrollment in phase I dose-expansion and phase II. Only data from phase 1 dose-escalation portion of the trial was reported. ^b Data from phase I part was reported here. ^c Only data from phase II part was reported. MTD maximal tolerated dose. BID twice daily. PFS progression-free survival. HR hazard ratio. CI confidential interval