1. Phase Ib/II ECHO-202/KEYNOTE-037: Epacadostat + Pembrolizumab in Pts With Advanced Urothelial Carcinoma
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 + Pembrolizumab in Advanced Urothelial Carcinoma: Background
Multiple immune checkpoint inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, pembrolizumab) recently approved for pts with advanced UC after platinum-based chemotherapy[1-6]
Pembrolizumab FDA approved in this setting based on phase III KEYNOTE data[6]
Atezolizumab, pembrolizumab also approved for first-line therapy in cisplatin- ineligible pts[7,8]
Epacadostat: potent, selective, PO inhibitor of tryptophan-degrading enzyme IDO1; promotes immunosurveillance in tumor microenvironment[9]
Current analysis from multicohort phase Ib/II trial evaluating safety, efficacy of epacadostat + pembrolizumab focuses on advanced UC cohort in phase II portion of study[10]
UC, urothelial carcinoma.
References:
1. Rosenberg JE, et al. Lancet. 2016;387:
2. Patel MR, et al. ASCO GU Abstract 330.
3. Powles T, et al. ASCO GU Abstract 286.
4. Sharma P, et al. Lancet Oncol. 2017;18:
5. Apolo AB, et al. J Clin Oncol. 2017;[Epub ahead of print].
6. Bellmunt J, et al. N Engl J Med. 2017;376:
7. Balar AV, et al. Lancet. 2017;389:67-76.
8. Balar AV, et al. ASCO GU Abstract 284.
9. Liu X, et al. Blood. 2010;115:
10. Smith DC, et al. ASCO Abstract 4503.
Slide credit: clinicaloptions.com
References in slidenotes.

3. ECHO-202/KEYNOTE-037: Study Design
Open-label dose escalation phase Ib study: adults with histologically or cytologically confirmed advanced/recurrent cancer, ECOG PS 0/1, and no prior immune checkpoint inhibitor or IDO1 inhibitor
Phase II: PD during/following platinum-based therapy in adjuvant or advanced disease setting; tumor cohorts included melanoma, SCCHN, UC, NSCLC, RCC, TNBC, OC, MSI-high CRC, DLBCL, GC, and HCC
Current analysis in UC (N = 40): ORR, change in target lesions, TTR, DoR, safety, PD-L1 biomarker analysis
Phase Ib
Phase II
CRC, colorectal cancer; DLBCL, diffuse large B-cell lymphoma; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma; GC, gastric cancer; MSI, microsatellite instability; NSCLC, non-small-cell lung cancer; PD, progressive disease; PS, performance status; RCC, renal cell carcinoma; SCCHN, squamous cell carcinoma of the head and neck; TNBC, triple-negative breast cancer; TTR, time to response; UC, urothelial carcinoma.
Dose Escalation
Safety Expansion
Cohort Expansion
Epacadostat
25, 50, 100, or 300 mg BID +
Pembrolizumab
2 mg/kg or 200 mg Q3W
Epacadostat
50, 100, or 300 mg BID +
Pembrolizumab
200 mg Q3W
Epacadostat
100 mg BID +
Pembrolizumab
200 mg Q3W
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

4. ECHO-202/KEYNOTE-037: Baseline Characteristics
UC Pts (N = 40)
Median age, yrs (range)
67 (43-87)
Male, n (%)
30 (75)
White, n (%)
35 (88)
ECOG PS 0/1, n (%)
16 (40) / 24 (60)
Bellmunt risk score,* n (%) 1
≥ 2
5 (13)
21 (53)
14 (35)
Common sites of metastases
Lymph node
Lung
Bone
Liver
Skin or subcutaneous tissue
Other
23 (58)
16 (40)
9 (23)
8 (20)
1 (3)
Characteristic, n (%)
UC Pts (N = 40)
Prior radiation tx
10 (25)
Prior surgery
37 (93)
Prior tx for advanced disease
0† or 1
≥ 2
32 (80)
8 (20)
Prior platinum-based tx
Cisplatin
Carboplatin
31 (78)
12 (30)
PD-L1 expression
Positive (CPS ≥ 1%)
Negative (CPS < 1%)
NE, missing, or not done
11 (28)
21 (53)
CPS, combined positive score; ECOG, Eastern Cooperative Oncology Group; Hb, hemoglobin; NE, not evaluable; PS, performance status; tx, treatment; UC, urothelial carcinoma.
*Based on presence of liver mets, ECOG PS ≥ 1, Hb < 10 g/dL, time from last chemotherapy < 3 mos.
†Platinum-based adjuvant/neoadjuvant therapy given to pts with no prior tx for advanced UC..
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

5. ECHO-202/KEYNOTE-037: Pt Disposition
Median follow-up: wks (range: 3.6 to wks)
Median epacadostat exposure: 20.1 wks (range: 1 to 132+ wks)
Disposition, n
UC Pts (N = 40)
Treatment completed* 2
Treatment ongoing 11
Treatment discontinued
Disease progression
Adverse events
Patient decision
Death 27 18 5 3 1
UC, urothelial carcinoma.
*Treatment completed after 24 mos of therapy or in pts who elected to discontinue after CR following a minimum of 24 wks of therapy and ≥ 2 cycles of additional treatment beyond the date of CR.
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

6. ECHO-202/KEYNOTE-037: Best Objective Response (RECIST v1.1)
Outcome,
n (%)
UC Pts
(N = 40)
Prior Lines of Tx
PD-L1 Expression
0-1
(n = 32)
≥ 2
(n = 8)
CPS ≥ 1%
(n = 11)
CPS < 1%
Unknown
(n = 21)
ORR CR PR
14 (35)
3 (8)
11 (28)
12 (38)
3 (9)
9 (28)
2 (25)
7 (64)
1 (13)
6 (29)
3 (14) SD
7 (18)
7 (22)
1 (9)
5 (24)
DCR
21 (53)
19 (59)
8 (73)
11 (52) PD
10 (31)
4 (50)
2 (18)
6 (75) NE
5 (13)
4 (19)
CPS, combined positive score; DCR, disease control rate; ir, immune related; NE, not evaluable; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.
By irRECIST, ORR: 38% (4 CR, 11 PR); DCR: 60% (9 SD)
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

7. ECHO-202/KEYNOTE-037: Efficacy
44% of evaluable pts had ≥ 25% reduction in baseline target lesions
46% of pts with 0-1 prior lines of therapy
33% of pts with ≥ 2 prior lines of therapy
Responses seen in majority of PD-L1+ pts (CPS ≥ 1%)
Most responses durable, occurred early in course of tx
Ongoing responses: 10/14
Included 2 pts who completed tx, 3 pts with CR
Median DoR: wks (range: 9.7 to wks)
CPS, combined positive score; DoR, duration of response; tx, treatment.
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

8. ECHO-202/KEYNOTE-037: TRAEs
TRAE Occurring in ≥ 5% of Pts, n (%)
UC Pts (N = 40)
Any Grade
Grade 3/4
Any
28 (70)
9 (23)
Fatigue
13 (33)
1 (3)
Rash
8 (20)
3 (8)
Amylase increase
5 (13)
Pruritis
4 (10)
ALT increase
Chills
Lipase increase
Nausea
Arthralgia
2 (5)
AST increase
Dysgeusia
Flushing
Hyperglycemia
Dose interruption due to TRAEs: 11/40 (28%); none in > 1 pt
Dose reduction due to tx-related rash: 2/40 (5%)
D/c due to TRAE: 3/40 (8%)
Colitis, rash, COPD exacerbation, n = 1 each
AEs manageable with supportive care
No tx-related deaths
ALT, alanine aminotransferase; AST, aspartate aminotransferase; COPD, chronic obstructive pulmonary disorder; D/c, discontinuation; TRAE, treatment-related adverse events; tx, treatment; UC, urothelial carcinoma.
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

9. ECHO-202/KEYNOTE-037: AEs of Special Interest
AE of Special Interest,* n (%)
UC Pts (N = 40)
Any Grade
Grade 3/4
Any
6 (15)
3 (8)
Severe skin reaction†
Colitis
1 (3)
Hypothyroidism
Pneumonitis
Type I diabetes mellitus
AE, adverse event; UC, urothelial carcinoma.
*Immune-related AEs, regardless of investigator attribution to study treatment.
†Includes grade ≥ 3 rash and rash macular.
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

10. ECHO-202/KEYNOTE-037: Conclusions
In pts with advanced urothelial carcinoma, combination epacadostat + pembrolizumab active and well tolerated
ORR: 35%; DCR: 53%; median DoR: wks; 10/14 ongoing responses
Higher response rate in PD-L1–positive pts, those with 0-1 vs ≥ 2 prior lines of treatment
Safety profile consistent with prior phase I/II data; greater frequency of grade 3/4 rash with combination vs pembrolizumab monotherapy
Study investigators suggest that data supports phase III trial of epacadostat + pembrolizumab in pts with urothelial carcinoma
DCR, disease control rate; DoR, duration of response.
Slide credit: clinicaloptions.com
Smith DC, et al. ASCO Abstract 4503.

11. 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
clinicaloptions.com/oncology