Clincosm LogoSign in Get a demo

A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)

Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT02752074
Collaborator
Merck Sharp & Dohme LLC (Industry)
706
Enrollment
129
Locations
2
Arms
37.8
Actual Duration (Months)
5.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the efficacy, safety, and tolerability when combining pembrolizumab with epacadostat or placebo in participants with unresectable or metastatic melanoma

Condition or Disease Intervention/Treatment Phase
  • Drug: pembrolizumab + epacadostat
  • Drug: pembrolizumab + placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
706 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Pembrolizumab (MK-3475) in Combination With Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)
Actual Study Start Date :
Jun 21, 2016
Actual Primary Completion Date :
Jan 8, 2018
Actual Study Completion Date :
Aug 16, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab + Epacadostat

Pembrolizumab + Epacadostat

Drug: pembrolizumab + epacadostat
Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) Epacadostat will be administered orally daily starting at Day 1 (Week 1)
Active Comparator: Pembrolizumab + Placebo

Pembrolizumab + Placebo

Drug: pembrolizumab + placebo
Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) Placebo will be administered orally daily starting at Day 1 (Week 1)

Outcome Measures

Primary Outcome Measures

  1. Progression-free Survival [Assessed every 9 weeks for duration of study participation which is estimated to be 24 months]

    Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first.

  2. Overall Survival (OS) Rate at 6 Months [Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.]

    Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.

Secondary Outcome Measures

  1. Objective Response Rate (ORR) [Assessed every 9 weeks for duration of study participation which is estimated to be 24 months]

    Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review.

  2. Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events [Through up to 90 days after end of treatment, up to 27 months]

    Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters.

  3. Duration of Response (DOR) [Assessed every 9 weeks for duration of study participation which is estimated to be 24 months]

    Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response.

  4. Apparent Oral Clearance (CL/F) of Epacadostat [Through up to 30 days after the end of treatment, up to 25 months]

    Defined as oral dose clearance.

  5. Apparent Volume of Distribution (Vd/F) of Epacadostat [Through up to 30 days after the end of treatment, up to 25 months]

    Apparent volume of distribution after administration.

  6. Clearance (CL) of Pembrolizumab [Through up to 30 days after the end of treatment, up to 25 months]

  7. Volume of Distribution (V) of Pembrolizumab [Through up to 30 days after the end of treatment, up to 25 months]

  8. Formation of Anti-pembrolizumab Antibodies [Through up to 30 days after the end of treatment, up to 25 months]

    Evaluate the measurement of anti-drug antibodies (ADA).

Eligibility Criteria

Criteria

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

  • Have histologically or cytologically confirmed melanoma

  • Have unresectable Stage III or Stage IV melanoma, as per AJCC staging system not amenable to local therapy

  • A minimum of 1 measurable lesion by CT or MRI

  • Provide a baseline tumor biopsy

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

  • Has received prior systemic treatment for unresectable or metastatic melanoma (except BRAF directed therapy)

  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or IDO1 inhibitor or any other antibody or drug specifically targeting checkpoint pathways other than anti-CTLA-4 which is permitted in the adjuvant setting

  • Has received prior adjuvant therapy, monoclonal antibody or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer)

  • Has an active infection requiring systemic therapy

  • Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

  • Has known history of or is positive for Hepatitis B or Hepatitis C

  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment

Contacts and Locations

Locations

Site City State Country Postal Code
1 Birmingham Alabama United States
2 Scottsdale Arizona United States
3 Little Rock Arkansas United States
4 Los Angeles California United States
5 San Francisco California United States
6 Santa Barbara California United States
7 Santa Monica California United States
8 Aurora Colorado United States
9 Denver Colorado United States
10 Washington District of Columbia United States
11 Fort Lauderdale Florida United States
12 Jacksonville Florida United States
13 Ocala Florida United States
14 West Palm Beach Florida United States
15 Chicago Illinois United States
16 Peoria Illinois United States
17 Iowa City Iowa United States
18 Kansas City Kansas United States
19 Lutherville Maryland United States
20 Boston Massachusetts United States
21 Ann Arbor Michigan United States
22 Fridley Minnesota United States
23 Billings Montana United States
24 Omaha Nebraska United States
25 Las Vegas Nevada United States
26 Rochester New York United States
27 Charlotte North Carolina United States
28 Philadelphia Pennsylvania United States
29 Nashville Tennessee United States
30 Austin Texas United States
31 Dallas Texas United States
32 Salt Lake City Utah United States
33 Fairfax Virginia United States
34 Spokane Washington United States
35 Camperdown New South Wales Australia
36 Westmead New South Wales Australia
37 Wollstonecraft New South Wales Australia
38 Cairns Queensland Australia
39 Greenslopes Queensland Australia
40 Kurralta Park South Australia Australia
41 Melbourne Victoria Australia
42 Brussels Belgium
43 Gent Belgium
44 North Vancouver British Columbia Canada
45 Ottawa Ontario Canada
46 Toronto Ontario Canada
47 Montreal Quebec Canada
48 Santiago Chile
49 Vina del Mar Chile
50 Aarhus Denmark
51 Herlev Denmark
52 Odense C Denmark
53 Bordeaux France
54 Lille France
55 Marseille France
56 Paris France
57 Pierre Benite France
58 Reims France
59 Rennes France
60 Toulouse France
61 Villejuif France
62 Buxtehude Germany
63 Essen Germany
64 Hannover Germany
65 Kiel Germany
66 Tuebingen Germany
67 Cork Ireland
68 Dublin Ireland
69 Galway Ireland
70 Ramat Gan Israel
71 Bergamo Italy
72 Genova Italy
73 Milano Italy
74 Napoli Italy
75 Padova Italy
76 Siena Italy
77 Susono Sunto-gun Japan
78 Asahikawa Japan
79 Chuo Japan
80 Fukuoka Japan
81 Kagoshima Japan
82 Kumamoto Japan
83 Kurume Japan
84 Kyoto Japan
85 Matsumoto Japan
86 Nagoya Japan
87 Niigata Japan
88 Okayama Japan
89 Osaka Japan
90 Sapporo Japan
91 Sendai Japan
92 Tokyo Japan
93 Tsukuba Japan
94 Seoul Korea, Republic of
95 Chihuahua Mexico
96 Distrito Federal Mexico
97 Mexico City Mexico
98 Monterrey Mexico
99 Amsterdam Netherlands
100 Nijmegen Netherlands
101 Dunedin New Zealand
102 Tauranga New Zealand
103 Warszawa Poland
104 Istra Russian Federation
105 Moscow Russian Federation
106 Saint Petersburg Russian Federation
107 Johannesburg Gauteng South Africa
108 Sandton Gauteng South Africa
109 Groenkloof Pretoria South Africa
110 Cape Town Western Cape South Africa
111 Kraaifontein South Africa
112 Donostia-San Sebastian Guipuzcoa Spain
113 A Coruna Spain
114 Barcelona Spain
115 Madrid Spain
116 Pamplona Spain
117 San Sebastian Spain
118 Sevilla Spain
119 Valencia Spain
120 Göteborg Sweden
121 Lund Sweden
122 Stockholm Sweden
123 Uppsala Sweden
124 Zürich ZH Switzerland
125 Geneve Switzerland
126 Lausanne Switzerland
127 Edinburgh United Kingdom
128 London United Kingdom
129 Manchester United Kingdom

Sponsors and Collaborators

  • Incyte Corporation
  • Merck Sharp & Dohme LLC

Investigators

  • Study Director: Mark Jones, MD, Incyte Corporation

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02752074
Other Study ID Numbers:
  • INCB 24360-301 (ECHO-301)
First Posted:
Apr 26, 2016
Last Update Posted:
Aug 27, 2020
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Incyte Corporation
Melanoma
Metastatic Melanoma
Additional relevant MeSH terms:
Melanoma
Pembrolizumab

Study Results

Participant Flow

Recruitment Details This study was conducted at 135 centers in 23 countries
Pre-assignment Detail
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Period Title: Overall Study
STARTED 354 352
Treated 353 352
COMPLETED 198 209
NOT COMPLETED 156 143

Baseline Characteristics

Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo Total
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1). Total of all reporting groups
Overall Participants 354 352 706
Age, Customized (Count of Participants)
< 65 years
183
51.7%
193
54.8%
376
53.3%
≥ 65 years
171
48.3%
159
45.2%
330
46.7%
Sex: Female, Male (Count of Participants)
Female
137
38.7%
146
41.5%
283
40.1%
Male
217
61.3%
206
58.5%
423
59.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
36
10.2%
27
7.7%
63
8.9%
Not Hispanic or Latino
302
85.3%
306
86.9%
608
86.1%
Unknown or Not Reported
16
4.5%
19
5.4%
35
5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
40
11.3%
36
10.2%
76
10.8%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
White
311
87.9%
315
89.5%
626
88.7%
More than one race
2
0.6%
1
0.3%
3
0.4%
Unknown or Not Reported
1
0.3%
0
0%
1
0.1%
Eastern Cooperative Oncology Group (ECOG) (Count of Participants)
Fully active
261
73.7%
267
75.9%
528
74.8%
Restricted in physically strenuous activity
93
26.3%
85
24.1%
178
25.2%

Outcome Measures

1. Primary Outcome
Title Progression-free Survival
Description Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first.
Time Frame Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 354 352
Median (95% Confidence Interval) [months]
4.7
4.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Epacadostat, Pembrolizumab + Placebo
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.51711
Comments One-sided p-value based on log-rank test.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.83 to 1.21
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Overall Survival (OS) Rate at 6 Months
Description Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.
Time Frame Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants. OS was analyzed at the time of primary analysis at 6 months. An overall OS was not conducted after the primary analysis since all participants were unblinded, transitioned to monotherapy pembrolizumab and survival follow-up was discontinued.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 354 352
Median (95% Confidence Interval) [percent probability]
84.1
87.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Epacadostat
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.80666
Comments One-sided p-value based on log-rank test.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.86 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Objective Response Rate (ORR)
Description Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review.
Time Frame Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 354 352
Count of Participants [Participants]
121
34.2%
111
31.5%
4. Secondary Outcome
Title Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events
Description Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters.
Time Frame Through up to 90 days after end of treatment, up to 27 months

Outcome Measure Data

Analysis Population Description
All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 353 352
With one or more adverse events
346
97.7%
345
98%
Serious adverse events
99
28%
100
28.4%
5. Secondary Outcome
Title Duration of Response (DOR)
Description Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response.
Time Frame Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 354 352
Median (Full Range) [months]
NA
NA
6. Secondary Outcome
Title Apparent Oral Clearance (CL/F) of Epacadostat
Description Defined as oral dose clearance.
Time Frame Through up to 30 days after the end of treatment, up to 25 months

Outcome Measure Data

Analysis Population Description
All randomized participants enrolled in the Epacadostat arm currently with melanoma.
Arm/Group Title Pembrolizumab + Epacadostat
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 340
Mean (Standard Deviation) [Liter/hour (L/h)]
59.8
(17.5)
7. Secondary Outcome
Title Apparent Volume of Distribution (Vd/F) of Epacadostat
Description Apparent volume of distribution after administration.
Time Frame Through up to 30 days after the end of treatment, up to 25 months

Outcome Measure Data

Analysis Population Description
All randomized participants enrolled in the Epacadostat arm currently with melanoma.
Arm/Group Title Pembrolizumab + Epacadostat
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 340
Mean (Standard Deviation) [Liter]
139
(22.5)
8. Secondary Outcome
Title Clearance (CL) of Pembrolizumab
Description
Time Frame Through up to 30 days after the end of treatment, up to 25 months

Outcome Measure Data

Analysis Population Description
The data was not available nor was the analysis completed for pembrolizumab CL, because participants were unblinded and sample collections and the planned analysis for pembrolizumab CL were discontinued after the interim analysis.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 0 0
9. Secondary Outcome
Title Volume of Distribution (V) of Pembrolizumab
Description
Time Frame Through up to 30 days after the end of treatment, up to 25 months

Outcome Measure Data

Analysis Population Description
The data was not available nor was the analysis completed for pembrolizumab V, because participants were unblinded and sample collections and the planned analysis for pembrolizumab V were discontinued after the interim analysis.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 0 0
10. Secondary Outcome
Title Formation of Anti-pembrolizumab Antibodies
Description Evaluate the measurement of anti-drug antibodies (ADA).
Time Frame Through up to 30 days after the end of treatment, up to 25 months

Outcome Measure Data

Analysis Population Description
Data was not available nor the analysis completed for the incidence of ADA to pembrolizumab, because all participants were unblinded; sample collections and the planned analysis for ADA were discontinued after the interim analysis.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Measure Participants 0 0

Adverse Events

Time Frame up to 27 months.
Adverse Event Reporting Description All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Arm/Group Description Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1). Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
All Cause Mortality
Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 147/353 (41.6%) 136/352 (38.6%)
Serious Adverse Events
Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 99/353 (28%) 100/352 (28.4%)
Blood and lymphatic system disorders
Anaemia 1/353 (0.3%) 4/352 (1.1%)
Neutropenia 0/353 (0%) 1/352 (0.3%)
Thrombocytopenia 1/353 (0.3%) 0/352 (0%)
Cardiac disorders
Acute myocardial infarction 0/353 (0%) 1/352 (0.3%)
Atrial fibrillation 0/353 (0%) 1/352 (0.3%)
Congestive cardiomyopathy 1/353 (0.3%) 0/352 (0%)
Extrasystoles 1/353 (0.3%) 0/352 (0%)
Myocarditis 1/353 (0.3%) 0/352 (0%)
Supraventricular tachycardia 1/353 (0.3%) 0/352 (0%)
Ear and labyrinth disorders
Vertigo positional 0/353 (0%) 1/352 (0.3%)
Endocrine disorders
Adrenal insufficiency 4/353 (1.1%) 1/352 (0.3%)
Hypophysitis 1/353 (0.3%) 3/352 (0.9%)
Hypothyroidism 0/353 (0%) 1/352 (0.3%)
Eye disorders
Retinopathy 0/353 (0%) 1/352 (0.3%)
Gastrointestinal disorders
Abdominal pain 2/353 (0.6%) 1/352 (0.3%)
Autoimmune colitis 1/353 (0.3%) 1/352 (0.3%)
Colitis 4/353 (1.1%) 5/352 (1.4%)
Diarrhoea 9/353 (2.5%) 4/352 (1.1%)
Gastric haemorrhage 1/353 (0.3%) 0/352 (0%)
Gastritis 1/353 (0.3%) 0/352 (0%)
Gastrooesophageal reflux disease 1/353 (0.3%) 0/352 (0%)
Intussusception 0/353 (0%) 1/352 (0.3%)
Large intestinal obstruction 0/353 (0%) 1/352 (0.3%)
Nausea 1/353 (0.3%) 2/352 (0.6%)
Pancreatitis 1/353 (0.3%) 1/352 (0.3%)
Pancreatitis acute 1/353 (0.3%) 1/352 (0.3%)
Pancreatitis chronic 1/353 (0.3%) 0/352 (0%)
Rectal haemorrhage 0/353 (0%) 1/352 (0.3%)
Small intestinal obstruction 0/353 (0%) 2/352 (0.6%)
Vomiting 3/353 (0.8%) 1/352 (0.3%)
Colitis ischaemic 1/353 (0.3%) 0/352 (0%)
Upper gastrointestinal haemorrhage 1/353 (0.3%) 0/352 (0%)
General disorders
Asthenia 0/353 (0%) 1/352 (0.3%)
Chest pain 1/353 (0.3%) 1/352 (0.3%)
Death 2/353 (0.6%) 0/352 (0%)
Fatigue 1/353 (0.3%) 2/352 (0.6%)
General physical health deterioration 1/353 (0.3%) 1/352 (0.3%)
Pyrexia 4/353 (1.1%) 3/352 (0.9%)
Hepatobiliary disorders
Autoimmune hepatitis 2/353 (0.6%) 0/352 (0%)
Bile duct obstruction 1/353 (0.3%) 0/352 (0%)
Cholecystitis 1/353 (0.3%) 1/352 (0.3%)
Hepatic function abnormal 1/353 (0.3%) 0/352 (0%)
Hepatitis acute 0/353 (0%) 1/352 (0.3%)
Immune-mediated hepatitis 1/353 (0.3%) 1/352 (0.3%)
Hepatitis 1/353 (0.3%) 0/352 (0%)
Immune system disorders
Anaphylactic reaction 1/353 (0.3%) 0/352 (0%)
Cytokine release syndrome 0/353 (0%) 1/352 (0.3%)
Drug hypersensitivity 0/353 (0%) 1/352 (0.3%)
Infections and infestations
Cellulitis 1/353 (0.3%) 1/352 (0.3%)
Dacryocanaliculitis 0/353 (0%) 1/352 (0.3%)
Erysipelas 0/353 (0%) 1/352 (0.3%)
Infected skin ulcer 1/353 (0.3%) 0/352 (0%)
Infection 1/353 (0.3%) 1/352 (0.3%)
Peritonitis 1/353 (0.3%) 0/352 (0%)
Pneumonia 5/353 (1.4%) 0/352 (0%)
Pseudomonas infection 1/353 (0.3%) 0/352 (0%)
Respiratory tract infection 1/353 (0.3%) 0/352 (0%)
Rhinitis 1/353 (0.3%) 0/352 (0%)
Sepsis 2/353 (0.6%) 2/352 (0.6%)
Septic shock 0/353 (0%) 2/352 (0.6%)
Urinary tract infection 1/353 (0.3%) 0/352 (0%)
Urosepsis 1/353 (0.3%) 0/352 (0%)
Viral infection 0/353 (0%) 1/352 (0.3%)
Wound infection 1/353 (0.3%) 0/352 (0%)
Lung infection 1/353 (0.3%) 0/352 (0%)
Injury, poisoning and procedural complications
Infusion related reaction 0/353 (0%) 1/352 (0.3%)
Lumbar vertebral fracture 0/353 (0%) 1/352 (0.3%)
Pubis fracture 1/353 (0.3%) 0/352 (0%)
Radiation necrosis 1/353 (0.3%) 0/352 (0%)
Thoracic vertebral fracture 1/353 (0.3%) 0/352 (0%)
Upper limb fracture 0/353 (0%) 1/352 (0.3%)
Wound complication 1/353 (0.3%) 0/352 (0%)
Concussion 1/353 (0.3%) 0/352 (0%)
Femoral neck fracture 0/353 (0%) 1/352 (0.3%)
Femur fracture 1/353 (0.3%) 0/352 (0%)
Humerus fracture 1/353 (0.3%) 0/352 (0%)
Lower limb fracture 0/353 (0%) 1/352 (0.3%)
Spinal compression fracture 0/353 (0%) 1/352 (0.3%)
Investigations
Alanine aminotransferase increased 1/353 (0.3%) 1/352 (0.3%)
Aspartate aminotransferase increased 0/353 (0%) 1/352 (0.3%)
Blood creatinine increased 2/353 (0.6%) 1/352 (0.3%)
Blood potassium increased 0/353 (0%) 1/352 (0.3%)
Metabolism and nutrition disorders
Decreased appetite 1/353 (0.3%) 1/352 (0.3%)
Dehydration 1/353 (0.3%) 0/352 (0%)
Diabetes mellitus 0/353 (0%) 1/352 (0.3%)
Diabetic ketoacidosis 1/353 (0.3%) 1/352 (0.3%)
Hypercalcaemia 1/353 (0.3%) 0/352 (0%)
Hypokalaemia 0/353 (0%) 1/352 (0.3%)
Hyponatraemia 0/353 (0%) 2/352 (0.6%)
Type 1 diabetes mellitus 0/353 (0%) 1/352 (0.3%)
Hyperglycaemia 0/353 (0%) 1/352 (0.3%)
Type 2 diabetes mellitus 1/353 (0.3%) 0/352 (0%)
Musculoskeletal and connective tissue disorders
Back pain 2/353 (0.6%) 1/352 (0.3%)
Dupuytren's contracture 1/353 (0.3%) 0/352 (0%)
Lumbar spinal stenosis 1/353 (0.3%) 0/352 (0%)
Myositis 0/353 (0%) 1/352 (0.3%)
Pathological fracture 1/353 (0.3%) 1/352 (0.3%)
Polymyalgia rheumatica 0/353 (0%) 1/352 (0.3%)
Scleroderma 1/353 (0.3%) 0/352 (0%)
Pain in extremity 0/353 (0%) 1/352 (0.3%)
Haemarthrosis 0/353 (0%) 1/352 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma 2/353 (0.6%) 4/352 (1.1%)
Breast cancer 1/353 (0.3%) 0/352 (0%)
Cancer pain 0/353 (0%) 1/352 (0.3%)
Malignant melanoma 0/353 (0%) 1/352 (0.3%)
Malignant melanoma in situ 0/353 (0%) 1/352 (0.3%)
Renal cell carcinoma 0/353 (0%) 1/352 (0.3%)
Squamous cell carcinoma 3/353 (0.8%) 3/352 (0.9%)
Squamous cell carcinoma of skin 1/353 (0.3%) 0/352 (0%)
T-cell lymphoma 1/353 (0.3%) 0/352 (0%)
Transitional cell carcinoma 0/353 (0%) 2/352 (0.6%)
Tumour flare 1/353 (0.3%) 0/352 (0%)
Tumour haemorrhage 0/353 (0%) 1/352 (0.3%)
Carcinoid tumour of the gastrointestinal 1/353 (0.3%) 0/352 (0%)
Follicular thyroid cancer 0/353 (0%) 1/352 (0.3%)
Intestinal adenocarcinoma 1/353 (0.3%) 0/352 (0%)
Nervous system disorders
Chronic inflammatory demyelinating polyradiculoneuropathy 1/353 (0.3%) 0/352 (0%)
Dizziness 1/353 (0.3%) 1/352 (0.3%)
Generalised tonic-clonic seizure 1/353 (0.3%) 0/352 (0%)
Haemorrhage intracranial 0/353 (0%) 5/352 (1.4%)
Hemiplegia 1/353 (0.3%) 0/352 (0%)
Ischaemic cerebral infarction 1/353 (0.3%) 0/352 (0%)
Ischaemic stroke 1/353 (0.3%) 0/352 (0%)
Neuralgia 1/353 (0.3%) 1/352 (0.3%)
Presyncope 0/353 (0%) 2/352 (0.6%)
Syncope 1/353 (0.3%) 2/352 (0.6%)
Tension headache 0/353 (0%) 1/352 (0.3%)
Cerebrovascular accident 0/353 (0%) 1/352 (0.3%)
Optic neuritis 1/353 (0.3%) 0/352 (0%)
Seizure 0/353 (0%) 1/352 (0.3%)
Psychiatric disorders
Anxiety 1/353 (0.3%) 0/352 (0%)
Paranoia 1/353 (0.3%) 0/352 (0%)
Renal and urinary disorders
Acute kidney injury 2/353 (0.6%) 3/352 (0.9%)
Bladder outlet obstruction 1/353 (0.3%) 0/352 (0%)
Hydronephrosis 0/353 (0%) 1/352 (0.3%)
Nephritis 1/353 (0.3%) 0/352 (0%)
Nephrolithiasis 0/353 (0%) 1/352 (0.3%)
Renal failure 0/353 (0%) 1/352 (0.3%)
Renal injury 0/353 (0%) 1/352 (0.3%)
Bladder perforation 1/353 (0.3%) 0/352 (0%)
Haematuria 0/353 (0%) 1/352 (0.3%)
Nephrotic syndrome 0/353 (0%) 1/352 (0.3%)
Tubulointerstitial nephritis 1/353 (0.3%) 0/352 (0%)
Ureterolithiasis 0/353 (0%) 1/352 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure 1/353 (0.3%) 0/352 (0%)
Bronchial obstruction 1/353 (0.3%) 0/352 (0%)
Bronchitis chronic 0/353 (0%) 1/352 (0.3%)
Chronic obstructive pulmonary disease 2/353 (0.6%) 1/352 (0.3%)
Dyspnoea 0/353 (0%) 1/352 (0.3%)
Haemoptysis 1/353 (0.3%) 0/352 (0%)
Pleural effusion 0/353 (0%) 1/352 (0.3%)
Pleurisy 1/353 (0.3%) 0/352 (0%)
Pneumonia aspiration 2/353 (0.6%) 0/352 (0%)
Pneumonitis 5/353 (1.4%) 3/352 (0.9%)
Pulmonary embolism 2/353 (0.6%) 2/352 (0.6%)
Pulmonary infarction 0/353 (0%) 1/352 (0.3%)
Emphysema 1/353 (0.3%) 0/352 (0%)
Interstitial lung disease 1/353 (0.3%) 0/352 (0%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative 1/353 (0.3%) 0/352 (0%)
Drug reaction with eosinophilia and systemic symptoms 1/353 (0.3%) 2/352 (0.6%)
Erythema multiforme 0/353 (0%) 1/352 (0.3%)
Lichen planus 0/353 (0%) 1/352 (0.3%)
Rash 2/353 (0.6%) 0/352 (0%)
Skin ulcer 1/353 (0.3%) 0/352 (0%)
Urticaria 0/353 (0%) 1/352 (0.3%)
Dermatitis allergic 0/353 (0%) 1/352 (0.3%)
Vascular disorders
Deep vein thrombosis 1/353 (0.3%) 1/352 (0.3%)
Essential hypertension 1/353 (0.3%) 0/352 (0%)
Haematoma 1/353 (0.3%) 0/352 (0%)
Hypertension 1/353 (0.3%) 0/352 (0%)
Hypotension 0/353 (0%) 2/352 (0.6%)
Lymphoedema 1/353 (0.3%) 0/352 (0%)
Thrombosis 0/353 (0%) 1/352 (0.3%)
Other (Not Including Serious) Adverse Events
Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 327/353 (92.6%) 325/352 (92.3%)
Blood and lymphatic system disorders
Anaemia 35/353 (9.9%) 36/352 (10.2%)
Endocrine disorders
Hyperthyroidism 22/353 (6.2%) 27/352 (7.7%)
Hypothyroidism 44/353 (12.5%) 35/352 (9.9%)
Gastrointestinal disorders
Abdominal pain 37/353 (10.5%) 37/352 (10.5%)
Abdominal pain upper 24/353 (6.8%) 16/352 (4.5%)
Constipation 58/353 (16.4%) 62/352 (17.6%)
Diarrhoea 90/353 (25.5%) 100/352 (28.4%)
Dry mouth 19/353 (5.4%) 30/352 (8.5%)
Nausea 103/353 (29.2%) 86/352 (24.4%)
Vomiting 51/353 (14.4%) 44/352 (12.5%)
General disorders
Asthenia 68/353 (19.3%) 46/352 (13.1%)
Fatigue 100/353 (28.3%) 94/352 (26.7%)
Oedema peripheral 27/353 (7.6%) 27/352 (7.7%)
Pyrexia 46/353 (13%) 38/352 (10.8%)
Influenza like Illness 17/353 (4.8%) 22/352 (6.3%)
Infections and infestations
Nasopharyngitis 50/353 (14.2%) 50/352 (14.2%)
Upper respiratory tract infection 19/353 (5.4%) 33/352 (9.4%)
Urinary tract infection 20/353 (5.7%) 32/352 (9.1%)
Influenza 19/353 (5.4%) 17/352 (4.8%)
Investigations
Alanine aminotransferase increased 39/353 (11%) 25/352 (7.1%)
Amylase increased 27/353 (7.6%) 34/352 (9.7%)
Aspartate aminotransferase increased 36/353 (10.2%) 33/352 (9.4%)
Lipase increased 36/353 (10.2%) 39/352 (11.1%)
Weight decreased 22/353 (6.2%) 17/352 (4.8%)
Metabolism and nutrition disorders
Decreased appetite 55/353 (15.6%) 44/352 (12.5%)
Hyperglycaemia 23/353 (6.5%) 17/352 (4.8%)
Musculoskeletal and connective tissue disorders
Arthralgia 63/353 (17.8%) 63/352 (17.9%)
Back pain 47/353 (13.3%) 52/352 (14.8%)
Myalgia 26/353 (7.4%) 32/352 (9.1%)
Pain in extremity 32/353 (9.1%) 28/352 (8%)
Nervous system disorders
Dizziness 33/353 (9.3%) 32/352 (9.1%)
Headache 66/353 (18.7%) 74/352 (21%)
Psychiatric disorders
Anxiety 19/353 (5.4%) 14/352 (4%)
Insomnia 35/353 (9.9%) 31/352 (8.8%)
Respiratory, thoracic and mediastinal disorders
Cough 73/353 (20.7%) 63/352 (17.9%)
Dyspnoea 22/353 (6.2%) 29/352 (8.2%)
Skin and subcutaneous tissue disorders
Dry skin 23/353 (6.5%) 23/352 (6.5%)
Pruritus 83/353 (23.5%) 101/352 (28.7%)
Rash 77/353 (21.8%) 81/352 (23%)
Rash maculo-papular 21/353 (5.9%) 18/352 (5.1%)
Vitiligo 51/353 (14.4%) 48/352 (13.6%)
Vascular disorders
Hypertension 27/353 (7.6%) 21/352 (6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Clinical Study Agreement.

Results Point of Contact

Name/Title Study Director
Organization Incyte Corporation
Phone 855-463-3463
Email medinfo@incyte.com
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02752074
Other Study ID Numbers:
  • INCB 24360-301 (ECHO-301)
First Posted:
Apr 26, 2016
Last Update Posted:
Aug 27, 2020
Last Verified:
Jul 1, 2020