Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03361865
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 93
• Locations: 143
• Arms: 2
• Actual Duration (Months): 32
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

Condition or Disease	Intervention/Treatment	Phase
UC (Urothelial Cancer)	Drug: Pembrolizumab; Drug: Epacadostat; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
• Actual Study Start Date: Dec 4, 2017
• Actual Primary Completion Date: Aug 9, 2018
• Actual Study Completion Date: Aug 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab 200 mg + epacadostat 100 mg BID Pembrolizumab + epacadostat	Drug: Pembrolizumab; Pembrolizumab administered intravenously every 3 weeks.; Other Names: MK-3475 ; Drug: Epacadostat; Epacadostat administered orally twice daily.; Other Names: INCB024360
Active Comparator: Pembrolizumab 200 mg + placebo BID Pembrolizumab + placebo	Drug: Pembrolizumab; Pembrolizumab administered intravenously every 3 weeks.; Other Names: MK-3475 ; Drug: Placebo; Matching placebo administered orally twice daily.

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo [Week 9]

   ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date.

Secondary Outcome Measures

1. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) [Up to approximately 25 months]

   AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

2. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE [Up to approximately 25 months]

   AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.

• Measurable disease based on RECIST v1.1.

• Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.

• Have provided tissue for PD-L1 analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.

• Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to randomization.

• Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

• Disease that is suitable for local therapy administered with curative intent.

• Known additional malignancy that is progressing or has required active treatment within the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.

• Active autoimmune disease that has required systemic treatment in past 2 years.

• Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.

• Known history of or is positive for active hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.

• History of a gastrointestinal condition that in the opinion of the Investigator may affect oral drug absorption.

• History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.

• Use of protocol-defined prior/concomitant therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates PC- HOPE	Tucson	Arizona	United States	85704
2	University of California Irvine Medical Center	Orange	California	United States	92868
3	Yale Cancer Center	New Haven	Connecticut	United States	06511
4	Woodlands Medical Specialists, PA	Pensacola	Florida	United States	32503
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	Quincy Medical Group	Quincy	Illinois	United States	62301
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	GU Research Network-Urology Cancer Center	Omaha	Nebraska	United States	68130
9	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
10	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
11	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
12	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
13	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
15	Medical University of South Carolina-Hollings Cancer Center	Charleston	South Carolina	United States	29425
16	Tennessee Oncology, PLLC/The Sarah Cannon Research Institute	Chattanooga	Tennessee	United States	37404
17	University of Tennessee Medical Center Knoxville	Knoxville	Tennessee	United States	37920
18	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
19	Tennessee Oncology Nashville	Nashville	Tennessee	United States	37203
20	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
21	Texas Oncology-Memorial City	Houston	Texas	United States	77024
22	University of Washington	Seattle	Washington	United States	98195
23	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
24	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
25	Austin Health-Austin Hospital	Heidelberg	Victoria	Australia	3084
26	Adelaide Cancer Centre	Kurralta Park		Australia	5037
27	Macquarie University Hospital	Macquarie Park		Australia	2109
28	Institut Jules Bordet	Bruxelles		Belgium	1000
29	Grand Hopital de Charleroi - Site Notre Dame - Oncology	Charleroi		Belgium	6000
30	AZ Maria Middelares Gent	Gent		Belgium	9000
31	Universitair Ziekenhuis Gent	Gent		Belgium	9000
32	Hopital de Jolimont	Haine-Saint-Paul		Belgium	7100
33	AZ Nikolaas	Sint-Niklaas		Belgium	9100
34	GZA Sint Augustinus	Wilrijk		Belgium	2610
35	Moncton Hospital - Horizon Health Network	Moncton	New Brunswick	Canada	E1C 6Z8
36	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
37	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
38	Sunnybrook Health Science Centre	Toronto	Ontario	Canada	M4N 3M5
39	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
40	CHU de Quebec - Hotel-Dieu de Quebec	Québec	Quebec	Canada	G1R 2J6
41	Institut de Cancerologie de l Ouest Site Paul Papin	Angers		France	49055
42	CHU de Besancon	Besançon		France	25030
43	Institut Bergonie	Bordeaux		France	33076
44	Centre Jean Perrin	Clermont-Ferrand		France	63011
45	Institut Paoli Calmettes	Marseille		France	13009
46	Centre d Oncologie de Gentilly	Nancy		France	54100
47	Hopital Europeen Georges Pompidou	Paris		France	75908
48	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	69310
49	Institut Jean Godinot	Reims		France	51726
50	CHU de Strasbourg - Nouvel Hopital Civil	Strasbourg		France	67091
51	Institut Claudius Regaud	Toulouse		France	31059
52	C.H.U. de Tours - Hopital Bretonneau	Tours		France	37044
53	Institut Gustave Roussy	Villejuif		France	94805
54	Universitaetsklinikum Schleswig-Holstein. Campus Luebeck	Luebeck	Schleswig Holstein	Germany	23538
55	Universitaetsklinikum Duesseldorf	Duesseldorf		Germany	40225
56	Kliniken Essen Mitte	Essen		Germany	45136
57	Universitatsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
58	Universitaetsklinikum Jena	Jena		Germany	07747
59	Universitaetsklinikum Magdeburg A.o.R.	Magdeburg		Germany	39120
60	Klinikum rechts der Isar der Technischen Universitat	Muenchen		Germany	81675
61	Krankenhaus der Barmherzigen Brueder Trier	Trier		Germany	54292
62	Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
63	Cork University Hospital	Cork		Ireland
64	Adelaide & Meath Hospital (Incl NCH)	Dublin		Ireland	00024
65	University College Hospital Galway	Galway		Ireland	H91YR71
66	University Hospital Limerick	Limerick		Ireland	V94 F858
67	University Hospital Waterford	Waterford		Ireland	X91ER8E
68	Soroka Medical Center	Be'er Sheva		Israel	8410101
69	Rambam Health Care Campus	Haifa		Israel	31096
70	Meir Medical Center	Kfar Saba		Israel	4428164
71	Rabin Medical Center	Petach-Tikwa		Israel	49100
72	Chaim Sheba Medical Center	Ramat Gan		Israel	52621
73	Sourasky Medical Center	Tel Aviv		Israel	6423906
74	Assaf Harofeh Medical Center	Zerifin		Israel	70300
75	Medical Oncology Ospedale San Donato	Arezzo		Italy	52100
76	Istituto Tumori Giovanni Paolo II	Bari		Italy	70124
77	Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST	Meldola		Italy	47014
78	Istituto Nazionale dei Tumori	Milan		Italy	20133
79	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli		Italy	80131
80	Istituto Oncologico Veneto	Padova		Italy	35128
81	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
82	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
83	University of Tsukuba Hospital	Tsukuba	Ibaraki	Japan	305-8576
84	Nara Medical University Hospital	Kashihara	Nara	Japan	634-8522
85	Kindai University Hospital	Osakasayama	Osaka	Japan	589-8511
86	Yamaguchi University Hospital	Ube	Yamaguchi	Japan	755-8505
87	Tokushima University Hospital	Tokushima		Japan	770-8503
88	Medical Hospital, Tokyo Medical And Dental University	Tokyo		Japan	113-8519
89	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
90	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
91	Seoul National University Hospital	Seoul		Korea, Republic of	03080
92	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	03722
93	Asan Medical Center	Seoul		Korea, Republic of	05505
94	Samsung Medical Center	Seoul		Korea, Republic of	06351
95	Amphia Ziekenhuis	Breda	Brabant	Netherlands	4819EV
96	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands	1066 CX
97	VU University Medical Center	Amsterdam		Netherlands	1081 HV
98	Catharina Ziekenhuis	Eindhoven		Netherlands	5623 EJ
99	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
100	Erasmus MC	Rotterdam		Netherlands	3075 EA
101	Beskidzkie Centrum Onkologii im. Jana Pawla II	Bielsko-Biala		Poland	43-300
102	Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej	Jelenia Góra		Poland	58-506
103	Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego	Katowice		Poland	40-514
104	GLOBE Badania Kliniczne Oddzial we Wroclawiu	Komorowice		Poland	52-229
105	Europejskie Centrum Zdrowia Otwock	Otwock		Poland	05-400
106	Urologica Praktyka Lekarska Adam Marcheluk	Siedlce		Poland	08-110
107	Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie	Szczecin		Poland	70-111
108	Magodent Szpital Elblaska	Warszawa		Poland	01-748
109	Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne	Warszawa		Poland	02 616
110	Leningrad Regional Oncology Dispensary	Saint Petersburg	Leningrad Region, Vsevolozhsky District	Russian Federation	188663
111	Ivanovo Regional Oncology Dispensary	Ivanovo		Russian Federation	153013
112	N.N. Blokhin NMRCO	Moscow		Russian Federation	115478
113	Russian Scientific Center of Roentgenoradiology	Moscow		Russian Federation	117997
114	National Medical Research Radiological Centre	Moscow		Russian Federation	125284
115	Ryazan Regional Clinical Oncology Dispensary	Ryazan		Russian Federation	390046
116	Pokrovskaya City Hospital	Saint Petersburg		Russian Federation	199106
117	Clinic of Bashkortostan State Medical University	Ufa		Russian Federation	450081
118	Hospital Teresa Herrera - Chuac	A Coruña		Spain	15006
119	Hospital Infanta Cristina	Badajoz		Spain	06080
120	Hospital General Universitari Vall d Hebron	Barcelona		Spain	08035
121	ICO L Hospitalet	Hospitalet de Llobregat		Spain	08908
122	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
123	Xarxa Assistencial Universitaria Manresa	Manresa		Spain	08243
124	Consorci Hospitalari Parc Tauli de Sabadell	Sabadell		Spain	08208
125	Hospital Virgen del Rocio	Sevilla		Spain	41013
126	Taipei Veterans General Hospital	Taipei	Beitou	Taiwan	112
127	Chang Gung Medical Foundation - Kaohsiung	Kaohsiung		Taiwan	833
128	China Medical University Hospital	Taichung		Taiwan	40447
129	National Cheng Kung University Hospital	Tainan		Taiwan	704
130	National Taiwan University Hospital	Taipei		Taiwan	100
131	MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov	Dnipropetrovsk		Ukraine	49005
132	Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC	Dnipropetrovsk		Ukraine	49102
133	Kharkiv Regional Clinical Oncology Center	Kharkiv		Ukraine	61000
134	Kyiv City Clinical Oncology Center	Kyiv		Ukraine	03115
135	MI Odessa Regional Oncological Centre	Odesa		Ukraine	65055
136	RMI Sumy Regional Clinical Oncology Dispensary	Sumy		Ukraine	40022
137	Royal Marsden NHS Trust	Sutton	Surrey	United Kingdom	SM2 5PT
138	The Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G120YN
139	Barts Health NHS Trust - St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
140	Royal Free London NHS Foundation Trust	London		United Kingdom	NW3 2QG
141	Imperial College Healthcare NHS Trust	London		United Kingdom	W6 8RF
142	Plymouth Hospitals NHS Trust	Plymouth		United Kingdom	PL6 8DH
143	Sunderland Royal Hospital	Sunderland		United Kingdom	SR4 7TP

Sponsors and Collaborators

• Incyte Corporation
• Merck Sharp & Dohme LLC

Investigators

• Study Director: Mark Jones, MD, Incyte Corporation

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 13, 2018

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03361865
• Other Study ID Numbers: KEYNOTE-672/ECHO-307
• First Posted: Dec 5, 2017
• Last Update Posted: Dec 16, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Urothelial cancer, programmed cell death 1 (PD-1) inhibitor; indoleamine 2,3-dioxygenase (IDO) inhibitor
• Additional relevant MeSH terms: Carcinoma, Transitional Cell; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	This study was conducted at 47 centers in 15 countries.

Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab 200 mg + Placebo BID
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Period Title: Overall Study
STARTED	44	49
Intention-to-Treat (ITT)	44	49
All Participants as Treated (APaT)	43	49
COMPLETED	25	22
NOT COMPLETED	19	27

Baseline Characteristics

Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab 200 mg + Placebo BID	Total
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.	Total of all reporting groups
Overall Participants	44	49	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.3 (9.5)	72.4 (8.9)	72.8 (9.1)
Sex: Female, Male (Count of Participants)
Female	11 25%	11 22.4%	22 23.7%
Male	33 75%	38 77.6%	71 76.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.5%	0 0%	2 2.2%
Not Hispanic or Latino	35 79.5%	42 85.7%	77 82.8%
Unknown or Not Reported	7 15.9%	7 14.3%	14 15.1%
Race/Ethnicity, Customized (Count of Participants)
Asian	9 20.5%	8 16.3%	17 18.3%
White	33 75%	37 75.5%	70 75.3%
Missing	2 4.5%	4 8.2%	6 6.5%
Metastasis Status at Screening (Count of Participants)
Metastatic	38 86.4%	45 91.8%	83 89.2%
Advanced/Unresectable	6 13.6%	4 8.2%	10 10.8%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Description	ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date.
Time Frame	Week 9

Outcome Measure Data

Analysis Population Description

The Intention-to-Treat (ITT) population consisted of all randomized participants.

Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab 200 mg + Placebo BID
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Measure Participants	44	49
Number (95% Confidence Interval) [percentage of participants]	31.8 72.3%	24.5 50%

2. Secondary Outcome

Title	Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)
Description	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame	Up to approximately 25 months

Outcome Measure Data

Analysis Population Description

All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab 200 mg + Placebo BID
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Measure Participants	43	49
Count of Participants [Participants]	43 97.7%	47 95.9%

3. Secondary Outcome

Title	Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
Description	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame	Up to approximately 25 months

Outcome Measure Data

Analysis Population Description

All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab 200 mg + Placebo BID
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Measure Participants	43	49
Count of Participants [Participants]	11 25%	15 30.6%

Adverse Events

Time Frame	up to approximately 25 months
Adverse Event Reporting Description	The All Participants as Treated (APaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment. All-Cause Mortality was based on the ITT population and consisted of all randomized participants. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to the drug are excluded.
Arm/Group Title	Pembrolizumab 200 mg + Epacadostat 100 mg BID		Pembrolizumab 200 mg + Placebo BID		Total
Arm/Group Description	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.		Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.		Total
All Cause Mortality
	Pembrolizumab 200 mg + Epacadostat 100 mg BID		Pembrolizumab 200 mg + Placebo BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/43 (39.5%)		19/49 (38.8%)		36/92 (39.1%)
Serious Adverse Events
	Pembrolizumab 200 mg + Epacadostat 100 mg BID		Pembrolizumab 200 mg + Placebo BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/43 (53.5%)		23/49 (46.9%)		46/92 (50%)
Blood and lymphatic system disorders
Anaemia	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Cardiac disorders
Left ventricular dysfunction	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Myocarditis	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Supraventricular tachycardia	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Congenital, familial and genetic disorders
Huntington's disease	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Endocrine disorders
Hypophysitis	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Gastrointestinal disorders
Nausea	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Small intestinal obstruction	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
General disorders
Death	1/43 (2.3%)	1	1/49 (2%)	1	2/92 (2.2%)	2
Fatigue	0/43 (0%)	0	1/49 (2%)	2	1/92 (1.1%)	2
Pyrexia	0/43 (0%)	0	1/49 (2%)	2	1/92 (1.1%)	2
Hepatobiliary disorders
Hepatitis	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Hepatitis cholestatic	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Immune system disorders
Anaphylactic reaction	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Infections and infestations
Encephalitis	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Enterococcal bacteraemia	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Gastroenteritis	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Herpes zoster	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Lymph gland infection	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Pneumocystis jirovecii pneumonia	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Sepsis	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Urinary tract infection	3/43 (7%)	3	6/49 (12.2%)	10	9/92 (9.8%)	13
Urosepsis	2/43 (4.7%)	2	1/49 (2%)	2	3/92 (3.3%)	4
Injury, poisoning and procedural complications
Fall	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Gastrointestinal stoma complication	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Infusion related reaction	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Urinary tract stoma complication	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Metabolism and nutrition disorders
Hypercalcaemia	1/43 (2.3%)	1	1/49 (2%)	1	2/92 (2.2%)	2
Musculoskeletal and connective tissue disorders
Pathological fracture	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Lung neoplasm malignant	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Malignant neoplasm progression	8/43 (18.6%)	9	5/49 (10.2%)	5	13/92 (14.1%)	14
Nervous system disorders
Somnolence	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Transient ischaemic attack	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Product Issues
Device occlusion	2/43 (4.7%)	2	0/49 (0%)	0	2/92 (2.2%)	2
Renal and urinary disorders
Acute kidney injury	0/43 (0%)	0	2/49 (4.1%)	2	2/92 (2.2%)	2
Autoimmune nephritis	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Calculus bladder	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Chronic kidney disease	0/43 (0%)	0	3/49 (6.1%)	4	3/92 (3.3%)	4
Haematuria	2/43 (4.7%)	2	0/49 (0%)	0	2/92 (2.2%)	2
Nephropathy toxic	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Renal failure	1/43 (2.3%)	1	1/49 (2%)	1	2/92 (2.2%)	2
Renal impairment	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Pneumothorax	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Pulmonary embolism	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Skin and subcutaneous tissue disorders
Urticaria	1/43 (2.3%)	1	0/49 (0%)	0	1/92 (1.1%)	1
Vascular disorders
Hypertensive crisis	0/43 (0%)	0	1/49 (2%)	1	1/92 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab 200 mg + Epacadostat 100 mg BID		Pembrolizumab 200 mg + Placebo BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/43 (97.7%)		47/49 (95.9%)		89/92 (96.7%)
Blood and lymphatic system disorders
Anaemia	14/43 (32.6%)	14	9/49 (18.4%)	12	23/92 (25%)	26
Endocrine disorders
Hypothyroidism	3/43 (7%)	3	4/49 (8.2%)	4	7/92 (7.6%)	7
Gastrointestinal disorders
Abdominal pain	2/43 (4.7%)	2	6/49 (12.2%)	6	8/92 (8.7%)	8
Constipation	7/43 (16.3%)	10	7/49 (14.3%)	7	14/92 (15.2%)	17
Diarrhoea	10/43 (23.3%)	14	7/49 (14.3%)	9	17/92 (18.5%)	23
Dry mouth	0/43 (0%)	0	4/49 (8.2%)	4	4/92 (4.3%)	4
Nausea	6/43 (14%)	9	6/49 (12.2%)	6	12/92 (13%)	15
Vomiting	4/43 (9.3%)	4	7/49 (14.3%)	9	11/92 (12%)	13
General disorders
Asthenia	9/43 (20.9%)	9	10/49 (20.4%)	10	19/92 (20.7%)	19
Fatigue	6/43 (14%)	7	8/49 (16.3%)	9	14/92 (15.2%)	16
Oedema peripheral	3/43 (7%)	4	7/49 (14.3%)	10	10/92 (10.9%)	14
Pyrexia	5/43 (11.6%)	6	6/49 (12.2%)	8	11/92 (12%)	14
Infections and infestations
Nasopharyngitis	0/43 (0%)	0	4/49 (8.2%)	4	4/92 (4.3%)	4
Pneumonia	3/43 (7%)	3	2/49 (4.1%)	2	5/92 (5.4%)	5
Urinary tract infection	5/43 (11.6%)	5	11/49 (22.4%)	14	16/92 (17.4%)	19
Investigations
Alanine aminotransferase increased	4/43 (9.3%)	4	5/49 (10.2%)	7	9/92 (9.8%)	11
Amylase increased	4/43 (9.3%)	8	4/49 (8.2%)	4	8/92 (8.7%)	12
Aspartate aminotransferase increased	4/43 (9.3%)	4	5/49 (10.2%)	6	9/92 (9.8%)	10
Blood alkaline phosphatase increased	2/43 (4.7%)	2	5/49 (10.2%)	5	7/92 (7.6%)	7
Blood creatinine increased	5/43 (11.6%)	6	3/49 (6.1%)	6	8/92 (8.7%)	12
Creatinine renal clearance decreased	3/43 (7%)	3	0/49 (0%)	0	3/92 (3.3%)	3
Lipase increased	4/43 (9.3%)	4	4/49 (8.2%)	4	8/92 (8.7%)	8
Weight decreased	3/43 (7%)	3	4/49 (8.2%)	4	7/92 (7.6%)	7
Metabolism and nutrition disorders
Decreased appetite	5/43 (11.6%)	7	8/49 (16.3%)	8	13/92 (14.1%)	15
Hyperkalaemia	3/43 (7%)	3	4/49 (8.2%)	6	7/92 (7.6%)	9
Hyperuricaemia	3/43 (7%)	7	0/49 (0%)	0	3/92 (3.3%)	7
Hypoalbuminaemia	5/43 (11.6%)	5	2/49 (4.1%)	2	7/92 (7.6%)	7
Hypocalcaemia	4/43 (9.3%)	6	1/49 (2%)	1	5/92 (5.4%)	7
Hypokalaemia	0/43 (0%)	0	3/49 (6.1%)	4	3/92 (3.3%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	3/43 (7%)	3	3/49 (6.1%)	5	6/92 (6.5%)	8
Back pain	7/43 (16.3%)	7	8/49 (16.3%)	9	15/92 (16.3%)	16
Flank pain	1/43 (2.3%)	1	3/49 (6.1%)	3	4/92 (4.3%)	4
Musculoskeletal pain	1/43 (2.3%)	1	3/49 (6.1%)	3	4/92 (4.3%)	4
Pain in extremity	2/43 (4.7%)	2	3/49 (6.1%)	3	5/92 (5.4%)	5
Psychiatric disorders
Insomnia	3/43 (7%)	3	2/49 (4.1%)	2	5/92 (5.4%)	5
Renal and urinary disorders
Dysuria	3/43 (7%)	3	3/49 (6.1%)	3	6/92 (6.5%)	6
Haematuria	4/43 (9.3%)	5	7/49 (14.3%)	9	11/92 (12%)	14
Respiratory, thoracic and mediastinal disorders
Cough	4/43 (9.3%)	4	5/49 (10.2%)	6	9/92 (9.8%)	10
Dyspnoea	5/43 (11.6%)	5	3/49 (6.1%)	3	8/92 (8.7%)	8
Pneumonitis	4/43 (9.3%)	4	0/49 (0%)	0	4/92 (4.3%)	4
Skin and subcutaneous tissue disorders
Pruritus	10/43 (23.3%)	13	6/49 (12.2%)	7	16/92 (17.4%)	20
Rash	10/43 (23.3%)	12	14/49 (28.6%)	14	24/92 (26.1%)	26

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.