1214O - Epacadostat Plus Pembrolizumab in Patients With Advanced Melanoma: Phase 1 and 2 Efficacy and Safety Results From ECHO-202/KEYNOTE-037

Date 09 September 2017
Event ESMO 2017 Congress
Session Melanoma and other skin tumours
Topics Cancers in Adolescents and Young Adults (AYA)
Immunotherapy
Skin Cancers
Melanoma
Therapy
Presenter Omid Hamid
Citation Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377
Authors O. Hamid1, T.F. Gajewski2, A.E. Frankel3, T.M. Bauer4, A.J. Olszanski5, J.J. Luke6, A.S. Balmanoukian1, E.V. Schmidt7, B. Sharkey8, J. Maleski8, M.J. Jones8, T.C. Gangadhar9
  • 1Research, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 2Department Of Pathology And Department Of Medicine, Section Of Hematology/oncology, University of Chicago, Chicago/US
  • 3Internal Medicine, University of Texas Southwestern Medical Center, Dallas/US
  • 4Drug Development Unit, Sarah Cannon Research Institute/Tennessee Oncology, Nashville/US
  • 5Department Of Medical Hematology/oncology, Fox Chase Cancer Center, Philadelphia/US
  • 6Hematology/oncology, University of Chicago, Chicago/US
  • 7Oncology Clinical Research, Merck & Co., Inc., Kenilworth/US
  • 8Drug Development, Incyte Corporation, Wilmington/US
  • 9Medicine, Hematology/oncology Division, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US

Abstract

Background

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). We report phase 1 and 2 efficacy and safety data for patients (pts) with advanced melanoma (27Feb2017 data cutoff).

Methods

Pts previously treated with checkpoint inhibitors were excluded. 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.

Results

64 pts enrolled (phase 1, n = 22; phase 2, n = 42). Median age, 65; male, 70%; BRAF+, 30%; M1c disease, 52%. Median duration of follow-up was 253+ days (range, 5 to 904+ days). Among 54 efficacy evaluable pts, ORR was 56% (30/54; 8 CR, 22 PR) and DCR (CR+PR+SD) was 78% (42/54). In treatment-naïve pts (n = 45), ORR was 56% (25/45; 6 CR, 19 PR) and DCR was 78% (35/45). 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. Biomarker evaluation is ongoing.

Conclusions

Consistent with the phase 1 results, E + P continues to be well tolerated and showed promising clinical activity. A phase 3 study in pts who are treatment-naive for advanced melanoma is ongoing (NCT02752074).

Clinical trial identification

NCT02178722

Legal entity responsible for the study

Incyte Corporation, Wilmington, DE

Funding

Incyte Corporation, Wilmington, DE; Merck & Co., Inc., Kenilworth, NJ

Disclosure

O. Hamid: Advisory Board - Merck & Co., Inc, Amgen, Novartis, Roche, Bristol-Myers Squibb; Corporate-sponsored Research - Incyte Corporation (Institution), Merck & Co., Inc. (Institution); Speaker’s Bureau – Bristol-Myers Squibb, Genetech, Novartis, Amgen; Honoraria – Genetech, Bristol-Myers Squibb, Novartis. T.F. Gajewski: Advisory Board - Merck & Co., Inc; Corporate-sponsored Research - Incyte Corporation (Institution), Merck & Co., Inc. (Institution). T.M. Bauer: Corporate-sponsored Research - Incyte Corporation (Institution), Merck & Co., Inc. (Institution) A.J. Olszanski: Advisory Board - Merck & Co., Inc, Bristol-Myers Squib; Corporate-sponsored Research - Incyte Corporation (Institution), Merck & Co., Inc. (Institution), Bristol-Myers Squibb, Novartis, Teva, Takeda, Pfizer; Other Substantive Relationships - Data Safety Monitoring Board: Takeda. J.J. Luke: Consult: Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, Gilead, Novartis, Merck; Inst res supp: AbbVie, BostonBiomedical, Bristol-Myers Squibb, Celldex, Corvus, Delcath, 5Prime, Genentech, Immunocore, Incyte, Intensity, MedImmune, Macrogenics, Novartis, Pharmacyclics, Merck, Tesaro. A.S. Balmanoukian: Corporate-sponsored Research – MedImmune/AstraZeneca, Merck Serono, Genentech, Incyte Corporation (Institution), Merck & Co., Inc. (Institution); Other Substantive Relationships - Speaker’s Bureau at Bristol-Myers Squibb, Merck, Genentech, AstraZeneca. E.V. Schmidt: Employment and stock ownership at Merck & Co., Inc. B. Sharkey, J. Maleski, M.J. Jones: Employment and stock ownership at Incyte Corporation T.C. Gangadhar: Corporate-sponsored Research - Incyte Corporation (Institution), Merck & Co., Inc. (Institution), Bristol-Myers Squibb, Roche, Cerulean; Honoraria - Merck & Co., Inc., Novartis; Advisory Role - Bristol-Myers Squibb All other authors have declared no conflicts of interest.