Phase I/II ECHO-202/KEYNOTE-037: Safety of Epacadostat + Pembrolizumab in Solid Tumors CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

ECHO-202/KEYNOTE-037: Epacadostat + Pembrolizumab in Solid Tumors—Background Immune-targeting combination approaches may improve clinical outcomes in solid tumors but can also increase toxicity, especially immune-related AEs Safety of novel immunotherapy combinations must be evaluated Epacadostat: potent, selective inhibitor of tryptophan-degrading enzyme IDO1 Supports immunosurveillance in tumor microenvironment via tryptophan regulation In phase I, monotherapy well tolerated in advanced cancers ECHO-202/KEYNOTE-037: phase I/II evaluating safety, efficacy of epacadostat + pembrolizumab in multiple tumor types Current analysis: phase II safety and tolerability outcomes AE, adverse event. Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Phase I/II Study Design Open-label dose escalation study Adults with histologically or cytologically confirmed advanced/recurrent cancer ECOG PS 0/1 No prior immune checkpoint inhibitor or IDO1 inhibitor Phase Ib Phase II Dose Escalation Safety Expansion Cohort Expansion Epacadostat 25, 50, 100, or 300 mg BID + Pembrolizumab 2 mg/kg or 200 mg Q3W ECOG, Eastern Cooperative Oncology Group; PS, performance status. Epacadostat 50, 100, or 300 mg BID + Pembrolizumab 200 mg Q3W Epacadostat 100 mg BID + Pembrolizumab 200 mg Q3W Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Pt Characteristics Safety-Evaluable Pts (N = 294) Median age (range), yrs 63 (28-93) Female, % 51 White race, % 90 ECOG PS 0/1, % 52/46 Tumor type, % NSCLC Melanoma Ovarian Squamous cell carcinoma of head and neck TNBC Renal cell carcinoma Urothelial carcinoma DLBCL MSI-high colorectal cancer 16 14 13 12 7 1 DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; MSI, microsatellite instability; NSCLC, non-small-cell lung cancer; PS, performance status; TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Disposition Median follow-up: 23.1+ wks Median epacadostat exposure: 13.6 wks (range: 1.0+ to 70.7+) Disposition, n (%) Safety-Evaluable Pts (N = 294) Treatment completed 1 (< 1) Treatment ongoing 111 (38) Treatment discontinued Disease progression Adverse events Death Patient decision Physician decision Other 182 (62) 134 (46) 19 (6) 14 (5) 12 (4) 2 (1) Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Treatment-Related AEs Selected AE, % Any Treatment-Related AE Any AE of Special Interest* Any Grade Grade 3/4 All tumor types 67 18 11 4 NSCLC 61 17 15 Renal cell carcinoma 80 14 9 3 Urothelial carcinoma 69 26 SCC of head and neck 19 TNBC 6 Ovarian cancer 70 16 8 AE, adverse event; NSCLC, non-small-call lung cancer; SCC, squamous cell carcinoma; TNBC, triple-negative breast cancer. *AE with immune-related cause, regardless of whether attributed to study treatment. Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Safety Safety Outcome, % Safety-Evaluable Pts (N = 294) Treatment-related AE leading to dose interruption Rash Fatigue Lipase increased 18 3 Treatment-related AE leading to dose reduction 5 2 1 Treatment-related AE leading to discontinuation Arthralgia 4 <1 AE, adverse event. One treatment-related death due to respiratory failure; one case of possible serotonin syndrome (resolved within 1 wk) Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

ECHO-202/KEYNOTE-037: Conclusions Epacadostat + pembrolizumab combination treatment has acceptable safety and tolerability profile in range of advanced cancers Consistent with phase I data Low incidence of grade 3/4 treatment-related and immune-related adverse events across all tumor types Profile similar to pembrolizumab monotherapy Higher incidence of grade 3/4 rash with combination Ongoing phase III study to evaluate combination in unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252) Slide credit: clinicaloptions.com Hamid O, et al. ASCO 2017. Abstract 3012.

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