Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03260894
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 129
• Locations: 140
• Arms: 2
• Anticipated Duration (Months): 61.9
• Patients Per Site: 0.9
• 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 plus epacadostat compared to sunitinib or pazopanib in participants with locally advanced/metastatic renal cell carcinoma (mRCC) with a clear cell component who have not received prior systemic therapy for their mRCC.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma (RCC)	Drug: Pembrolizumab; Drug: Epacadostat; Drug: Sunitinib; Drug: Pazopanib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302)
• Actual Study Start Date: Dec 7, 2017
• Anticipated Primary Completion Date: Feb 4, 2023
• Anticipated Study Completion Date: Feb 4, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab + Epacadostat	Drug: Pembrolizumab; Pembrolizumab 200 mg administered intravenously every 3 weeks.; Other Names: MK-3475 ; Drug: Epacadostat; Epacadostat 100 mg administered orally twice daily.; Other Names: INCB024360
Active Comparator: SoC (Sunitinib or Pazopanib) Standard of care (SoC) (sunitinib or pazopanib monotherapy).	Drug: Sunitinib; Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle.; Other Names: Sutent SU11248 ; Drug: Pazopanib; Pazopanib 800 mg administered orally once daily.; Other Names: Votrient

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) [Minimum up to 6 months]

   ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.

Secondary Outcome Measures

1. Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Experiencing Adverse Events (AEs) [Data reported from start of study to data cutoff 28-Feb-2019, up to 15 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 SOC as Measured by the Number of Participants Discontinuing Study Drug Due to AEs [Data reported from start of study to data cutoff 28-Feb-2019, up to 15 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:

• Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features.

• Must not have received any prior systemic therapy for their mRCC.

• Measurable disease based on RECIST v1.1.

• Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion as required.

• Karnofsky performance status ≥ 70%.

• Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

• Use of protocol-defined prior/concomitant therapy.

• Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization.

• History of severe hypersensitivity reaction to study treatments or their excipients.

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

• Known additional malignancy that has progressed or has required active treatment in the last 3 years.

• Known active central nervous system metastases and/or carcinomatous meningitis.

• History of (noninfectious) pneumonitis that required steroids or current pneumonitis.

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

• Significant cardiac event within 12 months before Cycle 1 Day 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Oncology Hematology	Scottsdale	Arizona	United States	85258
2	Scottsdale Healthcare	Scottsdale	Arizona	United States	85258
3	Arizona Oncology Associates PC- HOPE	Tucson	Arizona	United States	85711
4	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	UC Irvine Comprehensive Cancer Center/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
6	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
7	Woodlands Medical Specialists, PA	Pensacola	Florida	United States	32503
8	Northside Hospital	Atlanta	Georgia	United States	30342
9	Atlanta Cancer Care - Conyers	Conyers	Georgia	United States	30094
10	Northwest Georgia Oncology Centers Pc	Marietta	Georgia	United States	30060
11	Rush University Medical Center	Chicago	Illinois	United States	60612
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
14	Southeast Nebraska Hematology & Oncology Consultants, P.C.	Lincoln	Nebraska	United States	68510
15	New York Oncology Hematology P.C	Albany	New York	United States	12208
16	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
17	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
18	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
19	University of Tennessee Erlanger Oncology & Hematology	Chattanooga	Tennessee	United States	37403
20	The West Clinic, P.C.	Germantown	Tennessee	United States	38138
21	US Oncology and Research	The Woodlands	Texas	United States	77380
22	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
23	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
24	Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
25	Shenandoah Oncology, P.C.	Winchester	Virginia	United States	22601
26	Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
27	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
28	Westmead Hospital	Westmead	New South Wales	Australia	2145
29	Cabrini Health	Malvern	Victoria	Australia	3144
30	Fiona Stanley Hospital	Murdoch		Australia	6150
31	Centro de pesquisa Porto Alegre	Porto Alegre	Florianopolis	Brazil	90610-000
32	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	Sao Paulo	Brazil	14784-400
33	Instituto do Cancer de Sao Paulo - ICESP	São Paulo	Sao Paulo	Brazil	01246-000
34	Hospital Sao Jose	São Paulo	Sao Paulo	Brazil	01321-001
35	Centro Avancado de Tratamento Oncologico - CENANTRON -	Belo Horizonte		Brazil	30130090
36	Hospital de Clinicas de Porto Alegre	Porto Alegre		Brazil	90035-903
37	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
38	Kingston Health Sciences Centre - KGH Site	Kingston	Ontario	Canada	K7L 2V7
39	Sunnybrook Health Sciences, Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
40	Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2
41	CIUSSS de la Mauricie-et-du-Centre-du-Quebec	Trois-Rivières	Quebec	Canada	G8Z 3R9
42	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec	Quebec		Canada	G1R 2J6
43	Clinica Alemana de Osorno	Osorno	Region De Los Lagos	Chile	5311089
44	Fundacion Arturo Lopez Perez FALP	Santiago		Chile	7500921
45	Pontificia Universidad Catolica de Chile	Santiago		Chile	8320000
46	Hospital Clinico Vina del Mar	Vina del Mar		Chile	2520000
47	Centre Antoine Lacassagne	Nice	Cedex 2	France	06189
48	CHU Besancon - Hopital Jean Minjoz	Besançon		France	25030
49	Hopital Saint Andre	Bordeaux		France	33075
50	Centre Francois Baclesse	Caen		France	14076
51	Hopital Prive Toulon Hyeres Sainte Marguerite	Hyeres		France	83400
52	Hopital Europeen Georges Pompidou	Paris		France	75015
53	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre Benite		France	69310
54	Clinique Sainte Anne	Strasbourg		France	67000
55	CHU de Strasbourg - Nouvel Hopital Civil	Strasbourg		France	67091
56	Institut Gustave Roussy	Villejuif		France	94805
57	Helios Klinikum Berlin Buch	Berlin		Germany	13125
58	Universitaetsklinikum der Technischen Universitaet Dresden	Dresden		Germany	01307
59	Universitaetsklinikum Essen	Essen		Germany	45147
60	Universitaetsklinikum Frankfurt	Frankfurt am Main		Germany	60590
61	Medizinische Hochschule Hannover	Hannover		Germany	30625
62	Universitaetsklinikum Jena	Jena		Germany	07747
63	Universitaetsklinikum Magdeburg. Klinik fuer Urologie	Magdeburg		Germany	39120
64	Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
65	Orszagos Onkologiai Intezet	Budapest	Pest	Hungary	1122
66	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg	Pozva	Hungary	8900
67	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar		Hungary	7400
68	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc		Hungary	3526
69	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet	Szolnok		Hungary	5000
70	Markusovszky Egyetemi Oktatokorhaz	Szombathely		Hungary	9700
71	Adelaide & Meath Hospital	Dublin		Ireland	00024
72	University Hospital Waterford	Waterford		Ireland	X91ER8E
73	Medical Oncology Ospedale San Donato	Arezzo		Italy	52100
74	Azienda Ospedaliera-Spedali Civili	Brescia		Italy	25123
75	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
76	A.O. Cardarelli	Napoli		Italy	80131
77	Policlinico San Matteo	Pavia		Italy	27100
78	Azienda Ospedaliera San Camillo Forlanini	Roma		Italy	00152
79	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
80	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
81	Sapporo Medical University Hospital	Sapporo	Hokkaido	Japan	060-8543
82	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
83	Nara Medical University Hospital	Kashihara	Nara	Japan	634-8522
84	Kindai University Hospital	Osakasayama	Osaka	Japan	589-8511
85	Saitama Medical University International Medical Center	Hidaka	Saitama	Japan	350-1298
86	Yamaguchi University Hospital	Ube	Yamaguchi	Japan	755-8505
87	Akita University Hospital	Akita		Japan	010-8543
88	Kyushu University Hospital	Fukuoka		Japan	812-8582
89	Niigata University Medical & Dental Hospital	Niigata		Japan	951-8520
90	Toranomon Hospital	Tokyo		Japan	105-8470
91	Nippon Medical School Hospital	Tokyo		Japan	113-8603
92	Keio University Hospital	Tokyo		Japan	160-8582
93	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam Do	Korea, Republic of	58128
94	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	03722
95	Asan Medical Center	Seoul		Korea, Republic of	05505
96	Samsung Medical Center	Seoul		Korea, Republic of	06351
97	Auckland City Hospital	Auckland	Grafton	New Zealand	1023
98	Helse Bergen HF Haukeland sykehus	Bergen		Norway	5053
99	Sykehuset Oestfold	Gralum		Norway	1714
100	Sorlandet sykehus HF	Kristiansand		Norway	4615
101	Akershus University Hospital	Lørenskog		Norway	1478
102	Oslo universitetssykehus	Oslo		Norway	0450
103	Universitetssykehuset i Nord Norge. Kreftavdelingen	Tromsø		Norway	9019
104	St Olavs Hospital	Trondheim		Norway	7030
105	Leningrad Regional Oncology Dispensary	Saint Petersburg	Leningrad Region, Vsevolozhsky District	Russian Federation	188663
106	Ivanovo regional oncology dispensary	Ivanovo		Russian Federation	153040
107	Russian Scientific Center of Roentgenoradiology	Moscow		Russian Federation	117997
108	Central Clinical Hospital with outpatient Clinic	Moscow		Russian Federation	121359
109	National Medical Research Radiology Centre	Moscow		Russian Federation	125284
110	Republican Clinical Oncology Dispensary of Republic of Bashkortostan	Ufa		Russian Federation	450054
111	Hospital Parc Tauli	Sabadell	Barcelona	Spain	08208
112	Hospital del Mar	Barcelona		Spain	08003
113	Hospital Germans Trias i Pujol	Barcelona		Spain	08916
114	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
115	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
116	Hospital Clinico Universitario de Santiago	Santiago de Compostela		Spain	15706
117	Instituto Valenciano de Oncologia	Valencia		Spain	46009
118	Chang Gung Med Foundation. Kaohsiung Branch	Kaohsiung		Taiwan	833
119	China Medical University Hospital	Taichung		Taiwan	40447
120	National Cheng Kung University Hospital	Tainan		Taiwan	70457
121	National Taiwan University Hospital	Taipei		Taiwan	10048
122	Taipei Veterans General Hospital	Taipei		Taiwan	112
123	Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi	Adana		Turkey	01250
124	Ankara Numune Education and Research Hospital	Ankara		Turkey	06100
125	Hacettepe University Medical Faculty	Ankara		Turkey	06100
126	Istanbul Universitesi Onkoloji Enstitusu	Istanbul		Turkey	34093
127	Istanbul Medeniyet Universitesi Goztepe EAH	Istanbul		Turkey	34732
128	Ege Universitesi Tıp Fakultesi	Izmir		Turkey	35040
129	Namik Kemal Universitesi Tip Fakultesi	Tekirdag		Turkey	59100
130	MI Kryviy Rih Center of Dnipropetrovsk Regional Council	Kryvyi Rih	Dnipropetrovsk Region	Ukraine	50048
131	Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov	Dnipropetrovs'k		Ukraine	49005
132	Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC	Dnipropetrovs'k		Ukraine	49102
133	MI Precarpathian Clinical Oncology Center	Ivano-Frankivs'k		Ukraine	76018
134	RMI Sumy Regional Clinical Oncology Dispensary	Sumy		Ukraine	40022
135	The Royal Marsden NHS Foundation Trust.	Sutton	Surrey	United Kingdom	SM2 5PT
136	Western General Hospital	Edinburgh		United Kingdom	EH4 2XU
137	Beatson Institute of Cancer Research	Glasgow		United Kingdom	G12 0YN
138	Barts Health NHS Trust - St Bartholomew s Hospital	London		United Kingdom	EC1A 7BE
139	The Royal Marsden Foundation Trust	London		United Kingdom	SW3 6JJ
140	The Christie NHS Foundation Trust	Manchester		United Kingdom	MB204BX

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 15, 2018

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03260894
• Other Study ID Numbers: KEYNOTE-679/ECHO-302; 2017-002259-26
• First Posted: Aug 24, 2017
• Last Update Posted: Jun 23, 2022
• Last Verified: Jun 1, 2022

• 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: Renal cell carcinoma; programmed cell death 1 (PD-1) inhibitor; indoleamine 2; 3-dioxygenase 1 (IDO1) inhibitor
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Pembrolizumab; Sunitinib

Study Results

Participant Flow

Recruitment Details	This study was conducted at 73 centers in 14 countries.

Arm/Group Title	Pembrolizumab + Epacadostat	SoC (Sunitinib or Pazopanib)
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.	Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily;4 weeks on, 2 weeks off for 6-wk cycle. Pazopanib 800 mg administered orally once daily.
Period Title: Overall Study
STARTED	64	65
Intention-to-Treat (ITT)	64	65
All Subjects as Treated (ASaT)	64	63
COMPLETED	18	15
NOT COMPLETED	46	50

Baseline Characteristics

Arm/Group Title	Pembrolizumab + Epacadostat	SoC (Sunitinib or Pazopanib)	Total
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.	Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily. Pazopanib 800 mg administered orally once daily.	Total of all reporting groups
Overall Participants	64	65	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (10.9)	62.1 (10.6)	62.5 (10.7)
Sex: Female, Male (Count of Participants)
Female	20 31.3%	15 23.1%	35 27.1%
Male	44 68.8%	50 76.9%	94 72.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 29.7%	14 21.5%	33 25.6%
Not Hispanic or Latino	43 67.2%	47 72.3%	90 69.8%
Unknown or Not Reported	2 3.1%	4 6.2%	6 4.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian Or Alaska Native	1 1.6%	0 0%	1 0.8%
Asian	10 15.6%	9 13.8%	19 14.7%
White	53 82.8%	56 86.2%	109 84.5%
ECOG Performance Scale (Count of Participants)
0	41 64.1%	35 53.8%	76 58.9%
1	23 35.9%	28 43.1%	51 39.5%
2	0 0%	2 3.1%	2 1.6%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC)
Description	ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
Time Frame	Minimum up to 6 months

Outcome Measure Data

Analysis Population Description

The Intention-to-Treat (ITT) population consisted of all randomized participants. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date 28FEB2019.

Arm/Group Title	Pembrolizumab + Epacadostat	SoC (Sunitinib or Pazopanib)
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.	Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily;4 weeks on, 2 weeks off for 6-wk cycle. Pazopanib 800 mg administered orally once daily.
Measure Participants	64	65
Complete Response (CR)	1.6 2.5%
Partial Response (PR)	29.7 46.4%	29.2 44.9%
Objective Response (CR+PR)	31.3 48.9%	29.2 44.9%

2. Secondary Outcome

Title	Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the 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	Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.

Outcome Measure Data

Analysis Population Description

The All Subjects as Treated (ASaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	Pembrolizumab + Epacadostat	SoC (Sunitinib or Pazopanib)
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.	Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily;4 weeks on, 2 weeks off for 6-wk cycle. Pazopanib 800 mg administered orally once daily.
Measure Participants	64	63
Count of Participants [Participants]	64 100%	63 96.9%

3. Secondary Outcome

Title	Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to 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	Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.

Outcome Measure Data

Analysis Population Description

The All Subjects as Treated (ASaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	Pembrolizumab + Epacadostat	SoC (Sunitinib or Pazopanib)
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.	Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily;4 weeks on, 2 weeks off for 6-wk cycle. Pazopanib 800 mg administered orally once daily.
Measure Participants	64	63
Count of Participants [Participants]	8 12.5%	6 9.2%

Adverse Events

Time Frame	Non-serious adverse events were reported from start of study, up to 30 days after last dose and serious adverse events up to 90 days after last dose are included, up to 15 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 + Epacadostat		SoC (Sunitinib or Pazopanib)
Arm/Group Description	Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily.		Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily;4 weeks on, 2 weeks off for 6-wk cycle. Pazopanib 800 mg administered orally once daily.
All Cause Mortality
	Pembrolizumab + Epacadostat		SoC (Sunitinib or Pazopanib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/64 (12.5%)		8/65 (12.3%)
Serious Adverse Events
	Pembrolizumab + Epacadostat		SoC (Sunitinib or Pazopanib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/64 (28.1%)		15/63 (23.8%)
Cardiac disorders
Acute coronary syndrome	1/64 (1.6%)		0/63 (0%)
Atrial fibrillation	1/64 (1.6%)		1/63 (1.6%)
Cardiac failure	0/64 (0%)		1/63 (1.6%)
Pericardial effusion	0/64 (0%)		1/63 (1.6%)
Endocrine disorders
Adrenal insufficiency	1/64 (1.6%)		0/63 (0%)
Gastrointestinal disorders
Diarrhoea	0/64 (0%)		1/63 (1.6%)
Gastrointestinal haemorrhage	1/64 (1.6%)		0/63 (0%)
Large intestine perforation	0/64 (0%)		1/63 (1.6%)
Nausea	0/64 (0%)		1/63 (1.6%)
Pancreatitis	0/64 (0%)		1/63 (1.6%)
Small intestinal obstruction	1/64 (1.6%)		0/63 (0%)
General disorders
Asthenia	1/64 (1.6%)		0/63 (0%)
Fatigue	1/64 (1.6%)		0/63 (0%)
Hepatobiliary disorders
Hepatobiliary disease	0/64 (0%)		1/63 (1.6%)
Infections and infestations
Bronchitis	1/64 (1.6%)		0/63 (0%)
Gangrene	1/64 (1.6%)		0/63 (0%)
Groin abscess	0/64 (0%)		1/63 (1.6%)
Influenza	0/64 (0%)		1/63 (1.6%)
Lung infection	0/64 (0%)		1/63 (1.6%)
Pneumonia	2/64 (3.1%)		0/63 (0%)
Sepsis	0/64 (0%)		1/63 (1.6%)
Septic shock	0/64 (0%)		1/63 (1.6%)
Upper respiratory tract infection	0/64 (0%)		1/63 (1.6%)
Urinary tract infection	0/64 (0%)		1/63 (1.6%)
Urosepsis	0/64 (0%)		1/63 (1.6%)
Wound infection	0/64 (0%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Humerus fracture	1/64 (1.6%)		0/63 (0%)
Investigations
Platelet count decreased	0/64 (0%)		1/63 (1.6%)
Metabolism and nutrition disorders
Decreased appetite	1/64 (1.6%)		0/63 (0%)
Hypercalcaemia	2/64 (3.1%)		0/63 (0%)
Hyponatraemia	1/64 (1.6%)		2/63 (3.2%)
Steroid diabetes	1/64 (1.6%)		0/63 (0%)
Nervous system disorders
Altered state of consciousness	0/64 (0%)		1/63 (1.6%)
Cerebral ischaemia	1/64 (1.6%)		0/63 (0%)
Seizure	0/64 (0%)		1/63 (1.6%)
Reproductive system and breast disorders
Prostatomegaly	0/64 (0%)		1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/64 (1.6%)		0/63 (0%)
Pleural effusion	1/64 (1.6%)		1/63 (1.6%)
Pulmonary embolism	0/64 (0%)		1/63 (1.6%)
Skin and subcutaneous tissue disorders
Rash generalised	1/64 (1.6%)		0/63 (0%)
Vascular disorders
Deep vein thrombosis	0/64 (0%)		1/63 (1.6%)
Thrombosis	1/64 (1.6%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Pembrolizumab + Epacadostat		SoC (Sunitinib or Pazopanib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/64 (95.3%)		61/63 (96.8%)
Blood and lymphatic system disorders
Anaemia	10/64 (15.6%)		12/63 (19%)
Thrombocytopenia	2/64 (3.1%)		4/63 (6.3%)
Endocrine disorders
Hyperthyroidism	5/64 (7.8%)		2/63 (3.2%)
Hypothyroidism	9/64 (14.1%)		12/63 (19%)
Gastrointestinal disorders
Abdominal distension	4/64 (6.3%)		1/63 (1.6%)
Abdominal pain	2/64 (3.1%)		5/63 (7.9%)
Abdominal pain upper	2/64 (3.1%)		5/63 (7.9%)
Constipation	9/64 (14.1%)		3/63 (4.8%)
Diarrhoea	13/64 (20.3%)		30/63 (47.6%)
Dry mouth	4/64 (6.3%)		2/63 (3.2%)
Dyspepsia	3/64 (4.7%)		7/63 (11.1%)
Nausea	22/64 (34.4%)		20/63 (31.7%)
Stomatitis	0/64 (0%)		4/63 (6.3%)
Vomiting	6/64 (9.4%)		12/63 (19%)
General disorders
Asthenia	2/64 (3.1%)		6/63 (9.5%)
Chest pain	5/64 (7.8%)		0/63 (0%)
Fatigue	12/64 (18.8%)		15/63 (23.8%)
Influenza like illness	2/64 (3.1%)		4/63 (6.3%)
Oedema peripheral	3/64 (4.7%)		4/63 (6.3%)
Pyrexia	5/64 (7.8%)		2/63 (3.2%)
Investigations
Alanine aminotransferase increased	8/64 (12.5%)		14/63 (22.2%)
Amylase increased	8/64 (12.5%)		9/63 (14.3%)
Aspartate aminotransferase increased	4/64 (6.3%)		16/63 (25.4%)
Blood alkaline phosphatase increased	6/64 (9.4%)		9/63 (14.3%)
Blood bilirubin increased	1/64 (1.6%)		9/63 (14.3%)
Blood creatinine increased	7/64 (10.9%)		7/63 (11.1%)
Blood lactate dehydrogenase increased	1/64 (1.6%)		5/63 (7.9%)
Lipase increased	6/64 (9.4%)		9/63 (14.3%)
Neutrophil count decreased	0/64 (0%)		4/63 (6.3%)
Platelet count decreased	1/64 (1.6%)		6/63 (9.5%)
Weight decreased	7/64 (10.9%)		2/63 (3.2%)
Metabolism and nutrition disorders
Decreased appetite	10/64 (15.6%)		12/63 (19%)
Hypercalcaemia	4/64 (6.3%)		2/63 (3.2%)
Hyponatraemia	3/64 (4.7%)		6/63 (9.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/64 (9.4%)		5/63 (7.9%)
Back pain	10/64 (15.6%)		9/63 (14.3%)
Musculoskeletal pain	6/64 (9.4%)		0/63 (0%)
Nervous system disorders
Dysgeusia	1/64 (1.6%)		8/63 (12.7%)
Headache	3/64 (4.7%)		9/63 (14.3%)
Psychiatric disorders
Insomnia	6/64 (9.4%)		3/63 (4.8%)
Renal and urinary disorders
Haematuria	4/64 (6.3%)		3/63 (4.8%)
Proteinuria	2/64 (3.1%)		5/63 (7.9%)
Respiratory, thoracic and mediastinal disorders
Cough	7/64 (10.9%)		6/63 (9.5%)
Dysphonia	3/64 (4.7%)		4/63 (6.3%)
Epistaxis	1/64 (1.6%)		4/63 (6.3%)
Skin and subcutaneous tissue disorders
Hair colour changes	0/64 (0%)		7/63 (11.1%)
Palmar-plantar erythrodysaesthesia syndrome	1/64 (1.6%)		14/63 (22.2%)
Pruritus	16/64 (25%)		1/63 (1.6%)
Rash	11/64 (17.2%)		5/63 (7.9%)
Rash maculo-papular	4/64 (6.3%)		3/63 (4.8%)
Vascular disorders
Hypertension	7/64 (10.9%)		23/63 (36.5%)

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.