Melanoma – Combination of PD-1/IDO1 shows promising activity

Tumors can evade immunosurveillance through upregulation of indoleamine 2,3-dioxygenase 1 (IDO1). Epacadostat (E) is a potent, selective inhibitor of the IDO1 enzyme. The combination of E + the PD-1 inhibitor pembrolizumab (P) is being evaluated in an open-label, phase 1/2 study in multiple tumor types (ECHO-202/KEYNOTE-037). Now the first results of the phase 1 and 2 efficacy and safety study for patients (pts) with advanced melanoma have been released.
Consistent with the phase 1 results, E + P continues to be well tolerated and showed promising clinical activity. A phase 3 study in patients (pts) who are treatment-naive for advanced melanoma is ongoing (NCT02752074).

Pts previously treated with checkpoint inhibitors were excluded in this study. Pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W) during phase 1. MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) was selected for phase 2. Responses were assessed in RECIST 1.1 evaluable pts.
64 pts were enrolled with a median age of 65; male, 70 %; BRAF+, 30 %; M1c disease, 52 %. The median duration of the follow-up was 253+ days. Among 54 efficacy evaluable pts, ORR was 56 % and DCR (CR+PR+SD) was 78%. In treatment-naïve pts (n = 45), ORR was 56% and DCR was 78 %. Among treatment-naïve pts receiving E 100 mg BID (n = 30), ORR was 60% (18/30; 2 CR, 16 PR). Responses were observed regardless of PD-L1 and BRAF mutation status.
At data cutoff, 28/30 responses in the melanoma cohort were ongoing (median duration of response = 287.5+ days, range 1+ to 763+ days). Median PFS was 12.4 mo; PFS rates at 6, 12, and 18 mo were 70 %, 54 %, and 50 %, respectively. In treatment-naïve pts, median PFS has not been reached; PFS rates at 6, 12, and 18 mo were 68 %, 52 %, and 52 %. The most common (> 15 %) all-grade treatment-related AEs (TRAEs) were fatigue (39.1 %), rash (32.8 %), pruritus (26.6%), and arthralgia (15.6 %). Grade ≥ 3 TRAEs were observed in 17.2 % of pts (most common: lipase increased, n = 4; rash, n = 3; and amylase increased, n = 2). 3 pts discontinued for TRAEs (lipase increased, n = 1; arthralgia, n = 2). No treatment-related deaths occurred.