1. ECHO-204: Preliminary Results of Phase I/II Trial of Epacadostat + Nivolumab in Advanced 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. Epacadostat + Immune Checkpoint Inhibition
Indoleamine-2,3-dioxygenase 1, intracellular enzyme that promotes tumor immune escape via tryptophan depletion[1]
Epacadostat, IDO1 inhibitor, inhibited tumor growth in animal model[2]
Immune checkpoint inhibitors facilitate anti-tumor immune response by preventing binding of PD-L1 to PD-1[3]
Current study explores safety, efficacy of combining epacadostat with immune checkpoint inhibitor in solid organ tumors[4]
Phase I dose-escalation study in all tumor types (primary endpoint: AEs, irAEs) followed by phase II open-label cohort expansion in recurrent melanoma, ovarian cancer, CRC, NSCLC, GBM, HNSCC, and DLBCL
AEs, adverse events; CRC, colorectal cancer; DLBCL, diffuse large B-cell lymphoma; GBM, glioblastoma; HNSCC, head and neck squamous cell carcinoma; irAEs, immune related adverse events; NSCLC, non-small-cell lung cancer.
1. Moon YW, et al. J Immunother Cancer. 2015;3: Liu X, et al. Blood. 2010;115: Sharma P, et al. Science. 2015;348: Perez RP, et al. ASCO Abstract 3003.
Slide credit: clinicaloptions.com

3. ECHO-204: TRAEs in Phase I Study
TRAEs Occurring in ≥ 15% Pts, n (%)
Epacadostat 25 mg BID + Nivolumab
(n = 3)
Epacadostat 50 mg BID + Nivolumab
(n = 6)
Epacadostat 100 mg BID + Nivolumab
(n = 14)
Epacadostat 300 mg BID + Nivolumab
(n = 13)
All Grade
Grade 3/4*
Total
3 (100)
3 (50)
1 (17)
11 (79)
1 (7)
9 (69)
5 (39)
Rash
3 (21)
2 (15)
Fatigue
2 (67)
2 (14)
1 (8)
Pruritus
3 (23)
*10 additional grade 3/4 events occurred in 1 patient each: ALT increase, amylase increase, AST increase, asthenia, hypopituitarism, hyponatremia, lipase increase, myoclonus, pancreatic insufficiency, tremor.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; TRAEs, treatment-related adverse events.
No dose-limiting toxicity observed during 42 days of follow-up
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.

4. ECHO-204: Phase II Study Design
Open-label cohort expansion
Adults with relapsed or metastatic advanced cancer;* ECOG PS 0/1; ALP, ALT, AST ≤ 2.5 x ULN; no previous IDO or ICI therapy†
(N = 230)
*Eligibility criteria:
- Melanoma: ≤ 1 treatment for metastatic disease
- HNSCC: ≤ 2 treatments for metastatic disease
- Ovarian cancer: epithelial with previous platinum/taxane-based therapy
- CRC: ≥ 1 treatment including VEGF inhibitor
- NSCLC: ≤ 1 treatment for metastatic disease
- GBM: 1 treatment with radiotherapy and temozolomide with documented relapse or recurrence
- Lymphoma: relapsed/refractory DLBCL
†Except anti–CTLA-4 agent as first-line treatment for metastatic melanoma
Epacadostat
100 mg or 300 mg BID +
Nivolumab 240 mg IV Q2W
Primary endpoints: ORR, landmark PFS (6 mos) in melanoma, HNSCC, ovarian cancer, CRC cohorts
Assessment every 8 wks
Secondary endpoints: safety, tolerability
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRC, colorectal cancer; DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; GBM, glioblastoma; HNSCC, head and neck squamous cell carcinoma; ICI, immune checkpoint inhibitor; MTD, maximum tolerated dose; NSCLC, non-small-cell lung cancer; PS, performance status; ULN, upper limit of normal; VEGF, vascular endothelial growth factor.
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.

5. ECHO-204 Phase II: Treatment-Naive Melanoma Cohort, Best Objective Response
Pts With Response, n (%)
All Pts
(N = 40)
Epacadostat Dose
PD-L1 Expression
100 mg BID
(n = 6)
300 mg BID
(n = 34)
Positive (≥ 1%)
(n = 7)
Negative (< 1%)
ORR (CR + PR)
25 (63)
6 (100)
19 (56)
5 (71)
2 (29) CR
2 (5)
2 (6)
1 (14) PR
23 (58)
17 (50)
4 (57) SD
10 (25)
10 (29)
3 (43)
DCR (CR + PR + SD)
35 (88)
29 (85)
7 (100) PD
4 (10)
4 (12)
Not assessed
1 (3)
DCR, disease control rate; DoR, duration of response; PD, progressive disease; SD, stable disease.
Median DoR in untreated melanoma pts: 16+ wks (range: < 1 to 41+ wks)
Outcomes in 10 pretreated melanoma pts: 20% ORR, 70% DCR
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.

6. Best Change From Baseline (%) Change From Baseline (%)
ECHO-204 Phase II: Treatment-Naive Melanoma Cohort, Target Lesion Change From Baseline
Epacadostat 100 mg BD
Epacadostat 300 mg BD
Off study treatment
First occurrence of new lesion
100
100 50 50
Best Change From Baseline (%)
Change From Baseline (%)
-50
-50
-100 {
-100
Pts 8 16 24 32 40 48 56
Wks
Perez RP, et al. ASCO Abstract Reproduced with permission.

7. ECHO-204 Phase II: HNSCC Cohort, Best Objective Response
Pts With Response, n (%)
All Pts
(N = 31)
Epacadostat Dose
PD-L1 Expression
HPV Status
100 mg BID
(n = 7)
300 mg BID
(n = 24)
Positive
(≥ 1%)
(n = 10)
Negative
(< 1%)
(n = 8)
HPV Associated
Non-HPV Associated
(n = 21)
ORR (CR + PR)
7 (23)
1 (14)
6 (25)
3 (30)
1 (13)
4 (19) CR
1 (3)
1 (4)
1 (5) PR
6 (19)
5 (21)
3 (14) SD
12 (39)
11 (46)
4 (40)
5 (63)
9 (43)
DCR (CR + PR + SD)
19 (61)
2 (29)
17 (71)
7 (70)
6 (75)
6 (60)
13 (62) PD
8 (26)
4 (57)
4 (17)
1 (10)
Not assessed
4 (13)
3 (13)
2 (20)
DCR, disease control rate; DoR, duration of response; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; PD, progressive disease; SD, stable disease.
Median DoR in HNSCC pts: 24+ wks (range: 8+ to 32+ wks)
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.

8. ECHO-204 Phase II: HNSCC Target Lesion Change From Baseline
Epacadostat 100 mg BD
Epacadostat 300 mg BD
Off study treatment
First occurrence of new lesion
100
100 50 50
Best Change From Baseline (%)
Change From Baseline (%)
-50
HNSCC, squamous cell carcinoma of the head and neck.
-50
-100 8 16 24 32 40 48 56
-100
Pts
Wks
Perez RP, et al. ASCO Abstract Reproduced with permission.

9. ECHO-204: Common TRAEs in Combined Phase II Study
TRAEs Occurring in ≥ 10% Pts, (%)
Epacadostat 100 mg BID + Nivolumab
(n = 69)
Epacadostat 300 mg BID + Nivolumab
(n = 161)
Grade 1/2
Grade 3/4*
Any TRAE 83 25 73 27
irAEs
Rash
Diarrhea
Pruritus
Increased AST 12 16 10 3 17 15 9 1
Other
Fatigue
Nausea
Decreased appetite 23 19 4 35 20 14
AST, aspartate aminotransferase; irAE, immune-related adverse event; TRAE, treatment-related adverse event.
*n = 18 additional grade 3/4 events occurring in ≥ 1% of pts are not shown.
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.

10. ECHO-204: Efficacy in Ovarian Cancer and CRC Cohorts
N = 29 ovarian cancer pts with efficacy data; 59% received ≥ 2 previous treatments for advanced disease
14% ORR (1 CR, 3 PR), 31% DCR (5 SD)
CR occurred in treatment-naive, BRCA-negative, PD-L1–positive pt
14% ORR (1 PR), 29% DCR (1 SD) in 7 pts with BRCA1/2 mutation
N = 26 CRC pts with efficacy data; 77% received ≥ 2 previous treatments for advanced disease
25% ORR and DCR (1 PR) in 4 pts with MSI CRC
0% ORR and 33% DCR (6 SD) in 18 pts with MSS CRC
CRC, colorectal cancer; DCR, disease control rate; MSI, microsatellite instability; MSS, microsatellite stable; SD, stable disease.
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.
Slide credit: clinicaloptions.com

11. ECHO-204: Investigator Conclusions
In pts with select advanced solid tumors, epacadostat + nivolumab generally well tolerated
Increased risk of grade 3/4 rash and discontinuation due to AEs with 300-mg dose epacadostat vs 100-mg dose
In pts with melanoma and HNSCC, epacadostat + nivolumab had clinical activity
ORR 63% in treatment-naive melanoma; 23% ORR in HNSCC
PD-L1 expression, HPV status did not affect efficacy
No efficacy observed in pts with refractory ovarian cancer or CRC
AE, adverse event; CRC, colorectal cancer; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus.
Slide credit: clinicaloptions.com
Perez RP, et al. ASCO Abstract 3003.
Slide credit: clinicaloptions.com

12. 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 cancer
Gastrointestinal cancer
Genitourinary cancer
Gynecologic cancers
Hematologic malignancies
Lung cancer
Skin cancer
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