Table 5 Profile of representative clinical trials of epacadostat

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]