Background: Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme-induced immunosuppression in the tumor microenvironment supports tumor cell evasion of immune surveillance. Epacadostat (E) is a potent and selective oral inhibitor of the IDO1 enzyme. ECHO-204 is an open-label, phase (P) 1/2 study of E plus PD-1 inhibitor nivolumab (N) in patients (pts) with advanced cancer. Updated efficacy and safety/tolerability outcomes for the P2, advanced (unresectable or stage IV) melanoma cohort are reported. Methods: Pts received E (100 or 300 mg PO BID) plus N (240 mg IV Q2W). Response was assessed every 8 weeks (RECIST v1.1). Safety/tolerability was assessed in pts receiving ≥1 study treatment dose. PD-L1 expression was assessed (Dako 28-8 assay; PD-L1 positive: ≥1% tumor cell staining). Results: As of 29 Oct 2017, all of the planned 50 pts were enrolled in the P2 expansion cohort (n = 40 treatment naive for advanced disease). Median (range) duration of follow-up was 417 days (70 to 617 days). Across all pts, overall response rate (ORR) was 62% (31/50; 9 complete response [CR], 22 partial response [PR]) and disease control rate (DCR; CR + PR + stable disease) was 78% (39/50). In treatment-naive pts, ORR was 65% (26/40; 8 CR, 18 PR) and DCR was 80% (32/40); responses were observed in both PD-L1-positive pts (75% ORR [9/12]; 92% DCR [11/12]) and PD-L1-negative pts (56% ORR [9/16]; 69% DCR [11/16]); the majority (88%; 23/26) of responses were ongoing at data cutoff; duration of response ranged 55+ to 565+ days (median not reached); rate of progression-free survival at 6 and 12 months was 77% and 63%, respectively (median not reached); and the rate of overall survival at 12 months was 92% (median not reached). In the overall population (N = 50), the rate of grade ≥3 treatment-related adverse events (TRAEs) was 48% with E 300 mg BID (n = 42; most common grade ≥3 TRAEs: rash [19%], ALT increase [12%]) and 13% with E 100 mg BID (n = 8; pneumonitis [13%] was the only grade ≥3 TRAE). Eight pts discontinued treatment due to TRAEs (all E 300 mg BID). There was no AE-related death. Conclusions: E + N continues to show promising antitumor activity in pts with advanced melanoma and is generally well tolerated. E 100 mg BID is the selected dose for P3 studies of E + N in pts with advanced cancer. Clinical trial information: NCT02327078