1. 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.

2. 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 Abstract 3012.

3. 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 Abstract 3012.

4. 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 Abstract 3012.

5. ECHO-202/KEYNOTE-037: Disposition
Median follow-up: 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 Abstract 3012.

6. 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 Abstract 3012.

7. 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 Abstract 3012.

8. 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 Abstract 3012.

9. Go Online for More CCO Coverage of ASCO 2017!
Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in:
Breast, gastrointestinal, genitourinary, lung, and skin cancers
Gynecologic and hematologic malignancies
clinicaloptions.com/oncology