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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02752074
Recruitment Status : Completed
First Posted : April 26, 2016
Results First Posted : May 15, 2019
Last Update Posted : August 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Incyte Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: pembrolizumab + epacadostat
Drug: pembrolizumab + placebo
Enrollment 706
Recruitment Details This study was conducted at 135 centers in 23 countries
Pre-assignment Details  
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Hide 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
Reason Not Completed
Lost to Follow-up             1             4
Death             146             129
Withdrawal by Subject             9             10
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo Total
Hide 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 Number of Baseline Participants 354 352 706
Hide Baseline Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 352 participants 706 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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 352 participants 706 participants
Female
137
  38.7%
146
  41.5%
283
  40.1%
Male
217
  61.3%
206
  58.5%
423
  59.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 352 participants 706 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
   5.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 352 participants 706 participants
American Indian or Alaska Native
0
   0.0%
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%
0
   0.0%
Black or African American
0
   0.0%
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
   0.0%
1
   0.1%
Eastern Cooperative Oncology Group (ECOG)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 352 participants 706 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%
1.Primary Outcome
Title Progression-free Survival
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Hide 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).
Overall Number of Participants Analyzed 354 352
Median (95% Confidence Interval)
Unit of Measure: months
4.7
(2.9 to 6.8)
4.9
(2.9 to 6.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Epacadostat, Pembrolizumab + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51711
Comments One-sided p-value based on log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.83 to 1.21
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) Rate at 6 Months
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 354 352
Median (95% Confidence Interval)
Unit of Measure: percent probability
84.1
(79.8 to 87.5)
87.2
(83.2 to 90.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Epacadostat
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80666
Comments One-sided p-value based on log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.86 to 1.49
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Hide 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).
Overall Number of Participants Analyzed 354 352
Measure Type: Count of Participants
Unit of Measure: Participants
121
  34.2%
111
  31.5%
4.Secondary Outcome
Title Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 353 352
Measure Type: Count of Participants
Unit of Measure: Participants
With one or more adverse events
346
  98.0%
345
  98.0%
Serious adverse events
99
  28.0%
100
  28.4%
5.Secondary Outcome
Title Duration of Response (DOR)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population: consists of all randomized participants.
Arm/Group Title Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Hide 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).
Overall Number of Participants Analyzed 354 352
Median (Full Range)
Unit of Measure: months
NA [1] 
(0.0 to NA)
NA [1] 
(0.0 to NA)
[1]
Median duration not reached due to participants remaining in response at the time of the data cutoff.
6.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of Epacadostat
Hide Description Defined as oral dose clearance.
Time Frame Through up to 30 days after the end of treatment, up to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants enrolled in the Epacadostat arm currently with melanoma.
Arm/Group Title Pembrolizumab + Epacadostat
Hide 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).
Overall Number of Participants Analyzed 340
Mean (Standard Deviation)
Unit of Measure: Liter/hour (L/h)
59.8  (17.5)
7.Secondary Outcome
Title Apparent Volume of Distribution (Vd/F) of Epacadostat
Hide Description Apparent volume of distribution after administration.
Time Frame Through up to 30 days after the end of treatment, up to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants enrolled in the Epacadostat arm currently with melanoma.
Arm/Group Title Pembrolizumab + Epacadostat
Hide 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).
Overall Number of Participants Analyzed 340
Mean (Standard Deviation)
Unit of Measure: Liter
139  (22.5)
8.Secondary Outcome
Title Clearance (CL) of Pembrolizumab
Hide Description [Not Specified]
Time Frame Through up to 30 days after the end of treatment, up to 25 months
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Volume of Distribution (V) of Pembrolizumab
Hide Description [Not Specified]
Time Frame Through up to 30 days after the end of treatment, up to 25 months
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Formation of Anti-pembrolizumab Antibodies
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
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
Hide 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 (%) Affected / at Risk (%)
Total   147/353 (41.64%)   136/352 (38.64%) 
Hide Serious Adverse Events
Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   99/353 (28.05%)   100/352 (28.41%) 
Blood and lymphatic system disorders     
Anaemia † 1  1/353 (0.28%)  4/352 (1.14%) 
Neutropenia † 1  0/353 (0.00%)  1/352 (0.28%) 
Thrombocytopenia † 1  1/353 (0.28%)  0/352 (0.00%) 
Cardiac disorders     
Acute myocardial infarction † 1  0/353 (0.00%)  1/352 (0.28%) 
Atrial fibrillation † 1  0/353 (0.00%)  1/352 (0.28%) 
Congestive cardiomyopathy † 1  1/353 (0.28%)  0/352 (0.00%) 
Extrasystoles † 1  1/353 (0.28%)  0/352 (0.00%) 
Myocarditis † 1  1/353 (0.28%)  0/352 (0.00%) 
Supraventricular tachycardia † 1  1/353 (0.28%)  0/352 (0.00%) 
Ear and labyrinth disorders     
Vertigo positional † 1  0/353 (0.00%)  1/352 (0.28%) 
Endocrine disorders     
Adrenal insufficiency † 1  4/353 (1.13%)  1/352 (0.28%) 
Hypophysitis † 1  1/353 (0.28%)  3/352 (0.85%) 
Hypothyroidism † 1  0/353 (0.00%)  1/352 (0.28%) 
Eye disorders     
Retinopathy † 1  0/353 (0.00%)  1/352 (0.28%) 
Gastrointestinal disorders     
Abdominal pain † 1  2/353 (0.57%)  1/352 (0.28%) 
Autoimmune colitis † 1  1/353 (0.28%)  1/352 (0.28%) 
Colitis † 1  4/353 (1.13%)  5/352 (1.42%) 
Diarrhoea † 1  9/353 (2.55%)  4/352 (1.14%) 
Gastric haemorrhage † 1  1/353 (0.28%)  0/352 (0.00%) 
Gastritis † 1  1/353 (0.28%)  0/352 (0.00%) 
Gastrooesophageal reflux disease † 1  1/353 (0.28%)  0/352 (0.00%) 
Intussusception † 1  0/353 (0.00%)  1/352 (0.28%) 
Large intestinal obstruction † 1  0/353 (0.00%)  1/352 (0.28%) 
Nausea † 1  1/353 (0.28%)  2/352 (0.57%) 
Pancreatitis † 1  1/353 (0.28%)  1/352 (0.28%) 
Pancreatitis acute † 1  1/353 (0.28%)  1/352 (0.28%) 
Pancreatitis chronic † 1  1/353 (0.28%)  0/352 (0.00%) 
Rectal haemorrhage † 1  0/353 (0.00%)  1/352 (0.28%) 
Small intestinal obstruction † 1  0/353 (0.00%)  2/352 (0.57%) 
Vomiting † 1  3/353 (0.85%)  1/352 (0.28%) 
Colitis ischaemic † 1  1/353 (0.28%)  0/352 (0.00%) 
Upper gastrointestinal haemorrhage † 1  1/353 (0.28%)  0/352 (0.00%) 
General disorders     
Asthenia † 1  0/353 (0.00%)  1/352 (0.28%) 
Chest pain † 1  1/353 (0.28%)  1/352 (0.28%) 
Death † 1  2/353 (0.57%)  0/352 (0.00%) 
Fatigue † 1  1/353 (0.28%)  2/352 (0.57%) 
General physical health deterioration † 1  1/353 (0.28%)  1/352 (0.28%) 
Pyrexia † 1  4/353 (1.13%)  3/352 (0.85%) 
Hepatobiliary disorders     
Autoimmune hepatitis † 1  2/353 (0.57%)  0/352 (0.00%) 
Bile duct obstruction † 1  1/353 (0.28%)  0/352 (0.00%) 
Cholecystitis † 1  1/353 (0.28%)  1/352 (0.28%) 
Hepatic function abnormal † 1  1/353 (0.28%)  0/352 (0.00%) 
Hepatitis acute † 1  0/353 (0.00%)  1/352 (0.28%) 
Immune-mediated hepatitis † 1  1/353 (0.28%)  1/352 (0.28%) 
Hepatitis † 1  1/353 (0.28%)  0/352 (0.00%) 
Immune system disorders     
Anaphylactic reaction † 1  1/353 (0.28%)  0/352 (0.00%) 
Cytokine release syndrome † 1  0/353 (0.00%)  1/352 (0.28%) 
Drug hypersensitivity † 1  0/353 (0.00%)  1/352 (0.28%) 
Infections and infestations     
Cellulitis † 1  1/353 (0.28%)  1/352 (0.28%) 
Dacryocanaliculitis † 1  0/353 (0.00%)  1/352 (0.28%) 
Erysipelas † 1  0/353 (0.00%)  1/352 (0.28%) 
Infected skin ulcer † 1  1/353 (0.28%)  0/352 (0.00%) 
Infection † 1  1/353 (0.28%)  1/352 (0.28%) 
Peritonitis † 1  1/353 (0.28%)  0/352 (0.00%) 
Pneumonia † 1  5/353 (1.42%)  0/352 (0.00%) 
Pseudomonas infection † 1  1/353 (0.28%)  0/352 (0.00%) 
Respiratory tract infection † 1  1/353 (0.28%)  0/352 (0.00%) 
Rhinitis † 1  1/353 (0.28%)  0/352 (0.00%) 
Sepsis † 1  2/353 (0.57%)  2/352 (0.57%) 
Septic shock † 1  0/353 (0.00%)  2/352 (0.57%) 
Urinary tract infection † 1  1/353 (0.28%)  0/352 (0.00%) 
Urosepsis † 1  1/353 (0.28%)  0/352 (0.00%) 
Viral infection † 1  0/353 (0.00%)  1/352 (0.28%) 
Wound infection † 1  1/353 (0.28%)  0/352 (0.00%) 
Lung infection † 1  1/353 (0.28%)  0/352 (0.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction † 1  0/353 (0.00%)  1/352 (0.28%) 
Lumbar vertebral fracture † 1  0/353 (0.00%)  1/352 (0.28%) 
Pubis fracture † 1  1/353 (0.28%)  0/352 (0.00%) 
Radiation necrosis † 1  1/353 (0.28%)  0/352 (0.00%) 
Thoracic vertebral fracture † 1  1/353 (0.28%)  0/352 (0.00%) 
Upper limb fracture † 1  0/353 (0.00%)  1/352 (0.28%) 
Wound complication † 1  1/353 (0.28%)  0/352 (0.00%) 
Concussion † 1  1/353 (0.28%)  0/352 (0.00%) 
Femoral neck fracture † 1  0/353 (0.00%)  1/352 (0.28%) 
Femur fracture † 1  1/353 (0.28%)  0/352 (0.00%) 
Humerus fracture † 1  1/353 (0.28%)  0/352 (0.00%) 
Lower limb fracture † 1  0/353 (0.00%)  1/352 (0.28%) 
Spinal compression fracture † 1  0/353 (0.00%)  1/352 (0.28%) 
Investigations     
Alanine aminotransferase increased † 1  1/353 (0.28%)  1/352 (0.28%) 
Aspartate aminotransferase increased † 1  0/353 (0.00%)  1/352 (0.28%) 
Blood creatinine increased † 1  2/353 (0.57%)  1/352 (0.28%) 
Blood potassium increased † 1  0/353 (0.00%)  1/352 (0.28%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  1/353 (0.28%)  1/352 (0.28%) 
Dehydration † 1  1/353 (0.28%)  0/352 (0.00%) 
Diabetes mellitus † 1  0/353 (0.00%)  1/352 (0.28%) 
Diabetic ketoacidosis † 1  1/353 (0.28%)  1/352 (0.28%) 
Hypercalcaemia † 1  1/353 (0.28%)  0/352 (0.00%) 
Hypokalaemia † 1  0/353 (0.00%)  1/352 (0.28%) 
Hyponatraemia † 1  0/353 (0.00%)  2/352 (0.57%) 
Type 1 diabetes mellitus † 1  0/353 (0.00%)  1/352 (0.28%) 
Hyperglycaemia † 1  0/353 (0.00%)  1/352 (0.28%) 
Type 2 diabetes mellitus † 1  1/353 (0.28%)  0/352 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  2/353 (0.57%)  1/352 (0.28%) 
Dupuytren's contracture † 1  1/353 (0.28%)  0/352 (0.00%) 
Lumbar spinal stenosis † 1  1/353 (0.28%)  0/352 (0.00%) 
Myositis † 1  0/353 (0.00%)  1/352 (0.28%) 
Pathological fracture † 1  1/353 (0.28%)  1/352 (0.28%) 
Polymyalgia rheumatica † 1  0/353 (0.00%)  1/352 (0.28%) 
Scleroderma † 1  1/353 (0.28%)  0/352 (0.00%) 
Pain in extremity † 1  0/353 (0.00%)  1/352 (0.28%) 
Haemarthrosis † 1  0/353 (0.00%)  1/352 (0.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma † 1  2/353 (0.57%)  4/352 (1.14%) 
Breast cancer † 1  1/353 (0.28%)  0/352 (0.00%) 
Cancer pain † 1  0/353 (0.00%)  1/352 (0.28%) 
Malignant melanoma † 1  0/353 (0.00%)  1/352 (0.28%) 
Malignant melanoma in situ † 1  0/353 (0.00%)  1/352 (0.28%) 
Renal cell carcinoma † 1  0/353 (0.00%)  1/352 (0.28%) 
Squamous cell carcinoma † 1  3/353 (0.85%)  3/352 (0.85%) 
Squamous cell carcinoma of skin † 1  1/353 (0.28%)  0/352 (0.00%) 
T-cell lymphoma † 1  1/353 (0.28%)  0/352 (0.00%) 
Transitional cell carcinoma † 1  0/353 (0.00%)  2/352 (0.57%) 
Tumour flare † 1  1/353 (0.28%)  0/352 (0.00%) 
Tumour haemorrhage † 1  0/353 (0.00%)  1/352 (0.28%) 
Carcinoid tumour of the gastrointestinal † 1  1/353 (0.28%)  0/352 (0.00%) 
Follicular thyroid cancer † 1  0/353 (0.00%)  1/352 (0.28%) 
Intestinal adenocarcinoma † 1  1/353 (0.28%)  0/352 (0.00%) 
Nervous system disorders     
Chronic inflammatory demyelinating polyradiculoneuropathy † 1  1/353 (0.28%)  0/352 (0.00%) 
Dizziness † 1  1/353 (0.28%)  1/352 (0.28%) 
Generalised tonic-clonic seizure † 1  1/353 (0.28%)  0/352 (0.00%) 
Haemorrhage intracranial † 1  0/353 (0.00%)  5/352 (1.42%) 
Hemiplegia † 1  1/353 (0.28%)  0/352 (0.00%) 
Ischaemic cerebral infarction † 1  1/353 (0.28%)  0/352 (0.00%) 
Ischaemic stroke † 1  1/353 (0.28%)  0/352 (0.00%) 
Neuralgia † 1  1/353 (0.28%)  1/352 (0.28%) 
Presyncope † 1  0/353 (0.00%)  2/352 (0.57%) 
Syncope † 1  1/353 (0.28%)  2/352 (0.57%) 
Tension headache † 1  0/353 (0.00%)  1/352 (0.28%) 
Cerebrovascular accident † 1  0/353 (0.00%)  1/352 (0.28%) 
Optic neuritis † 1  1/353 (0.28%)  0/352 (0.00%) 
Seizure † 1  0/353 (0.00%)  1/352 (0.28%) 
Psychiatric disorders     
Anxiety † 1  1/353 (0.28%)  0/352 (0.00%) 
Paranoia † 1  1/353 (0.28%)  0/352 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  2/353 (0.57%)  3/352 (0.85%) 
Bladder outlet obstruction † 1  1/353 (0.28%)  0/352 (0.00%) 
Hydronephrosis † 1  0/353 (0.00%)  1/352 (0.28%) 
Nephritis † 1  1/353 (0.28%)  0/352 (0.00%) 
Nephrolithiasis † 1  0/353 (0.00%)  1/352 (0.28%) 
Renal failure † 1  0/353 (0.00%)  1/352 (0.28%) 
Renal injury † 1  0/353 (0.00%)  1/352 (0.28%) 
Bladder perforation † 1  1/353 (0.28%)  0/352 (0.00%) 
Haematuria † 1  0/353 (0.00%)  1/352 (0.28%) 
Nephrotic syndrome † 1  0/353 (0.00%)  1/352 (0.28%) 
Tubulointerstitial nephritis † 1  1/353 (0.28%)  0/352 (0.00%) 
Ureterolithiasis † 1  0/353 (0.00%)  1/352 (0.28%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure † 1  1/353 (0.28%)  0/352 (0.00%) 
Bronchial obstruction † 1  1/353 (0.28%)  0/352 (0.00%) 
Bronchitis chronic † 1  0/353 (0.00%)  1/352 (0.28%) 
Chronic obstructive pulmonary disease † 1  2/353 (0.57%)  1/352 (0.28%) 
Dyspnoea † 1  0/353 (0.00%)  1/352 (0.28%) 
Haemoptysis † 1  1/353 (0.28%)  0/352 (0.00%) 
Pleural effusion † 1  0/353 (0.00%)  1/352 (0.28%) 
Pleurisy † 1  1/353 (0.28%)  0/352 (0.00%) 
Pneumonia aspiration † 1  2/353 (0.57%)  0/352 (0.00%) 
Pneumonitis † 1  5/353 (1.42%)  3/352 (0.85%) 
Pulmonary embolism † 1  2/353 (0.57%)  2/352 (0.57%) 
Pulmonary infarction † 1  0/353 (0.00%)  1/352 (0.28%) 
Emphysema † 1  1/353 (0.28%)  0/352 (0.00%) 
Interstitial lung disease † 1  1/353 (0.28%)  0/352 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis exfoliative † 1  1/353 (0.28%)  0/352 (0.00%) 
Drug reaction with eosinophilia and systemic symptoms † 1  1/353 (0.28%)  2/352 (0.57%) 
Erythema multiforme † 1  0/353 (0.00%)  1/352 (0.28%) 
Lichen planus † 1  0/353 (0.00%)  1/352 (0.28%) 
Rash † 1  2/353 (0.57%)  0/352 (0.00%) 
Skin ulcer † 1  1/353 (0.28%)  0/352 (0.00%) 
Urticaria † 1  0/353 (0.00%)  1/352 (0.28%) 
Dermatitis allergic † 1  0/353 (0.00%)  1/352 (0.28%) 
Vascular disorders     
Deep vein thrombosis † 1  1/353 (0.28%)  1/352 (0.28%) 
Essential hypertension † 1  1/353 (0.28%)  0/352 (0.00%) 
Haematoma † 1  1/353 (0.28%)  0/352 (0.00%) 
Hypertension † 1  1/353 (0.28%)  0/352 (0.00%) 
Hypotension † 1  0/353 (0.00%)  2/352 (0.57%) 
Lymphoedema † 1  1/353 (0.28%)  0/352 (0.00%) 
Thrombosis † 1  0/353 (0.00%)  1/352 (0.28%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab + Epacadostat Pembrolizumab + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   327/353 (92.63%)   325/352 (92.33%) 
Blood and lymphatic system disorders     
Anaemia † 1  35/353 (9.92%)  36/352 (10.23%) 
Endocrine disorders     
Hyperthyroidism † 1  22/353 (6.23%)  27/352 (7.67%) 
Hypothyroidism † 1  44/353 (12.46%)  35/352 (9.94%) 
Gastrointestinal disorders     
Abdominal pain † 1  37/353 (10.48%)  37/352 (10.51%) 
Abdominal pain upper † 1  24/353 (6.80%)  16/352 (4.55%) 
Constipation † 1  58/353 (16.43%)  62/352 (17.61%) 
Diarrhoea † 1  90/353 (25.50%)  100/352 (28.41%) 
Dry mouth † 1  19/353 (5.38%)  30/352 (8.52%) 
Nausea † 1  103/353 (29.18%)  86/352 (24.43%) 
Vomiting † 1  51/353 (14.45%)  44/352 (12.50%) 
General disorders     
Asthenia † 1  68/353 (19.26%)  46/352 (13.07%) 
Fatigue † 1  100/353 (28.33%)  94/352 (26.70%) 
Oedema peripheral † 1  27/353 (7.65%)  27/352 (7.67%) 
Pyrexia † 1  46/353 (13.03%)  38/352 (10.80%) 
Influenza like Illness † 1  17/353 (4.82%)  22/352 (6.25%) 
Infections and infestations     
Nasopharyngitis † 1  50/353 (14.16%)  50/352 (14.20%) 
Upper respiratory tract infection † 1  19/353 (5.38%)  33/352 (9.38%) 
Urinary tract infection † 1  20/353 (5.67%)  32/352 (9.09%) 
Influenza † 1  19/353 (5.38%)  17/352 (4.83%) 
Investigations     
Alanine aminotransferase increased † 1  39/353 (11.05%)  25/352 (7.10%) 
Amylase increased † 1  27/353 (7.65%)  34/352 (9.66%) 
Aspartate aminotransferase increased † 1  36/353 (10.20%)  33/352 (9.38%) 
Lipase increased † 1  36/353 (10.20%)  39/352 (11.08%) 
Weight decreased † 1  22/353 (6.23%)  17/352 (4.83%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  55/353 (15.58%)  44/352 (12.50%) 
Hyperglycaemia † 1  23/353 (6.52%)  17/352 (4.83%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  63/353 (17.85%)  63/352 (17.90%) 
Back pain † 1  47/353 (13.31%)  52/352 (14.77%) 
Myalgia † 1  26/353 (7.37%)  32/352 (9.09%) 
Pain in extremity † 1  32/353 (9.07%)  28/352 (7.95%) 
Nervous system disorders     
Dizziness † 1  33/353 (9.35%)  32/352 (9.09%) 
Headache † 1  66/353 (18.70%)  74/352 (21.02%) 
Psychiatric disorders     
Anxiety † 1  19/353 (5.38%)  14/352 (3.98%) 
Insomnia † 1  35/353 (9.92%)  31/352 (8.81%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  73/353 (20.68%)  63/352 (17.90%) 
Dyspnoea † 1  22/353 (6.23%)  29/352 (8.24%) 
Skin and subcutaneous tissue disorders     
Dry skin † 1  23/353 (6.52%)  23/352 (6.53%) 
Pruritus † 1  83/353 (23.51%)  101/352 (28.69%) 
Rash † 1  77/353 (21.81%)  81/352 (23.01%) 
Rash maculo-papular † 1  21/353 (5.95%)  18/352 (5.11%) 
Vitiligo † 1  51/353 (14.45%)  48/352 (13.64%) 
Vascular disorders     
Hypertension † 1  27/353 (7.65%)  21/352 (5.97%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Clinical Study Agreement.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Incyte Corporation
Phone: 855-463-3463
EMail: medinfo@incyte.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02752074    
Other Study ID Numbers: INCB 24360-301 (ECHO-301)
First Submitted: April 22, 2016
First Posted: April 26, 2016
Results First Submitted: February 26, 2019
Results First Posted: May 15, 2019
Last Update Posted: August 27, 2020