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Trial record 69 of 519 for:    melanoma phase III

Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006)

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: NCT01866319
Recruitment Status : Completed
First Posted : May 31, 2013
Results First Posted : January 14, 2016
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Biological: Pembrolizumab
Biological: Ipilimumab
Enrollment 834
Recruitment Details Recruitment to the study has stopped; some participants are still receiving treatment.
Pre-assignment Details

These results are based on a database cutoff date of 03 Mar 2015, at which time, 497 participants were continuing in the study.

These data were collected and analyzed prior to the 02 Aug 2016 effective date of Amendment 05.

Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description Participants receive ipilimumab, 3 mg/kg intravenously (IV), once eveery 3 weeks (Q3W) for a total of 4 doses Participants receive pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to 2 years Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years
Period Title: Overall Study
Started 278 279 277
Treated 256 278 277
Completed 1 0 0
Not Completed 277 279 277
Reason Not Completed
Adverse Event             13             6             12
Clinical progression             1             0             0
Death             97             74             77
Lost to Follow-up             3             0             6
Physician Decision             1             0             0
Withdrawal by Subject             31             9             6
Remain on study             131             190             176
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W Total
Hide Arm/Group Description Participants receive ipilimumab, 3 mg/kg IV, Q3W for a total of 4 doses Participants receive pembrolizumab, 10 mg/kg IV, Q2W for up to 2 years Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years Total of all reporting groups
Overall Number of Baseline Participants 278 279 277 834
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants. Participants were included in the group to which they were randomized for Baseline Characteristics.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 278 participants 279 participants 277 participants 834 participants
59.9  (14.2) 59.9  (14.6) 61.2  (13.6) 60.3  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 279 participants 277 participants 834 participants
Female
116
  41.7%
118
  42.3%
103
  37.2%
337
  40.4%
Male
162
  58.3%
161
  57.7%
174
  62.8%
497
  59.6%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description

PFS was defined as the time from randomization to the first documented disease progression, based on blinded independent central radiologic and clinical review using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death due to any cause, whichever occurred first. Disease progression was defined as a 20% or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5mm or the appearance of new lesions.

Statistical testing was stratified by line of therapy (1st vs. 2nd), programmed cell death ligand 1 (PD-L1) status (positive vs. negative) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1)

Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants as randomized to a study arm; data collected up to 3 September 2014.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants receive ipilimumab, 3 mg/kg IV, Q3W for a total of 4 doses
Participants receive pembrolizumab, 10 mg/kg IV, Q2W for up to 2 years
Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years
Overall Number of Participants Analyzed 278 279 277
Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.8 to 2.9)
5.5
(3.4 to 6.9)
4.1
(2.9 to 6.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.46 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.47 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75869
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.77 to 1.21
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. The reported percentage is estimated using a product-limit (Kaplan-Meier) method for censored data; for participants whose survival data was obtained after the data cut-off date for the interim analysis, data were censored at the date of cut-off (3 March 2015). Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1).
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants as randomized to a study arm; data collected up to 3 March 2015.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants receive ipilimumab, 3 mg/kg IV, Q3W for a total of 4 doses
Participants receive pembrolizumab, 10 mg/kg IV, Q2W for up to 2 years
Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years
Overall Number of Participants Analyzed 278 279 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
58.2
(51.8 to 64.0)
74.1
(68.5 to 78.9)
68.4
(62.5 to 73.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00052
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.47 to 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00358
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.52 to 0.90
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51319
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval 95%
0.67 to 1.22
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description

ORR was defined as the percentage of the participants with a best tumor response of complete response (CR) or partial response (PR) based on blinded independent central radiologic and clinical review using RECIST 1.1. CR was defined as disappearance of all target lesions with any pathological lymph nodes having a reduction in short axis to <10 mm. PR was defined as a 30% or greater decrease in the sum of diameters of target lesions.

Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1)

Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants randomized to a study arm; data collected through 3 September 2014.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants receive ipilimumab, 3 mg/kg IV, Q3W for a total of 4 doses
Participants receive pembrolizumab, 10 mg/kg IV, Q2W for up to 2 years
Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years
Overall Number of Participants Analyzed 278 279 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
11.9
(8.3 to 16.3)
33.7
(28.2 to 39.6)
32.9
(27.4 to 38.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00013
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value 16.1
Confidence Interval (2-Sided) 95%
7.8 to 24.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00002
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value 17.2
Confidence Interval (2-Sided) 95%
9.5 to 25.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82636
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value -1.1
Confidence Interval 95%
-10.6 to 8.6
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) were collected for 30 days after the last dose of study drug (up to 25 months.
Adverse Event Reporting Description Data cut-off 3 March 2015; AEs were recorded for the all participants as treated (APaT) population, defined as all randomized patients who received at least one dose of study treatment.
 
Arm/Group Title Ipilimumab 3 mg/kg Q3W Pembrolizumab 10 mg/kg Q2W Pembrolizumab 10 mg/kg Q3W
Hide Arm/Group Description Participants receive ipilimumab, 3 mg/kg IV, Q3W for a total of 4 doses Participants receive pembrolizumab, 10 mg/kg IV, Q2W for up to 2 years Participants receive pembrolizumab, 10 mg/kg IV, Q3W for up to 2 years
All-Cause Mortality
Ipilimumab 3 mg/kg Q3W Pembrolizumab 10 mg/kg Q2W Pembrolizumab 10 mg/kg Q3W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab 3 mg/kg Q3W Pembrolizumab 10 mg/kg Q2W Pembrolizumab 10 mg/kg Q3W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   81/256 (31.64%)      90/278 (32.37%)      84/277 (30.32%)    
Blood and lymphatic system disorders       
Anaemia  1  0/256 (0.00%)  0 2/278 (0.72%)  2 5/277 (1.81%)  5
Lymphadenopathy  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Thrombocytopenia  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  3
Cardiac disorders       
Acute coronary syndrome  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Angina unstable  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Atrial fibrillation  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Atrial flutter  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cardiac failure  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Cardiac failure congestive  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  3
Cardio-respiratory arrest  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Myocardial infarction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pericardial effusion  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Endocrine disorders       
Adrenal insufficiency  1  1/256 (0.39%)  1 2/278 (0.72%)  2 0/277 (0.00%)  0
Hypophysitis  1  2/256 (0.78%)  2 0/278 (0.00%)  0 1/277 (0.36%)  1
Hypopituitarism  1  2/256 (0.78%)  2 1/278 (0.36%)  1 0/277 (0.00%)  0
Thyroiditis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Eye disorders       
Diplopia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Glaucoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Uveitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Gastrointestinal disorders       
Abdominal distension  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Abdominal pain  1  2/256 (0.78%)  2 1/278 (0.36%)  1 2/277 (0.72%)  2
Abdominal pain lower  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Anal fistula  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Autoimmune pancreatitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Colitis  1  16/256 (6.25%)  18 4/278 (1.44%)  4 6/277 (2.17%)  6
Constipation  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Diarrhoea  1  10/256 (3.91%)  10 10/278 (3.60%)  10 2/277 (0.72%)  2
Enteritis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Enterocolitis  1  2/256 (0.78%)  2 0/278 (0.00%)  0 0/277 (0.00%)  0
Gastritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Gastrointestinal haemorrhage  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Gastrooesophageal reflux disease  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Haematochezia  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Ileus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Intestinal obstruction  1  0/256 (0.00%)  0 2/278 (0.72%)  3 0/277 (0.00%)  0
Intestinal stenosis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Intussusception  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Large intestine perforation  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Nausea  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Oesophagitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pancreatitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Small intestinal obstruction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Stomatitis necrotising  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Vomiting  1  3/256 (1.17%)  3 0/278 (0.00%)  0 1/277 (0.36%)  1
General disorders       
Adverse drug reaction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Asthenia  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Cardiac death  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Death  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Face oedema  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Fatigue  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
General physical health deterioration  1  1/256 (0.39%)  1 2/278 (0.72%)  2 1/277 (0.36%)  1
Generalised oedema  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Malaise  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Pain  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pyrexia  1  4/256 (1.56%)  4 2/278 (0.72%)  3 0/277 (0.00%)  0
Hepatobiliary disorders       
Autoimmune hepatitis  1  1/256 (0.39%)  1 3/278 (1.08%)  3 1/277 (0.36%)  1
Bile duct obstruction  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Biliary dilatation  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cholangitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cholecystitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Drug-induced liver injury  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  2
Hepatic function abnormal  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Hepatitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Hepatocellular injury  1  2/256 (0.78%)  2 0/278 (0.00%)  0 0/277 (0.00%)  0
Hepatotoxicity  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Liver disorder  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Immune system disorders       
Anaphylactoid reaction  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Drug hypersensitivity  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypersensitivity  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Infections and infestations       
Bacterial sepsis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Bronchitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Cellulitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 2/277 (0.72%)  2
Clostridium difficile colitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Colonic abscess  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cystitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Encephalitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Endocarditis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Endocarditis staphylococcal  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Erysipelas  1  1/256 (0.39%)  1 1/278 (0.36%)  1 1/277 (0.36%)  1
Escherichia bacteraemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Gastroenteritis  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Liver abscess  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Lung infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Meningitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Myelitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pelvic infection  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pneumonia  1  3/256 (1.17%)  3 3/278 (1.08%)  3 1/277 (0.36%)  1
Pyelonephritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Respiratory tract infection  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Sepsis  1  2/256 (0.78%)  2 2/278 (0.72%)  2 2/277 (0.72%)  2
Septic shock  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Sinusitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Soft tissue infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Urinary tract infection  1  1/256 (0.39%)  1 1/278 (0.36%)  1 1/277 (0.36%)  1
Urosepsis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Injury, poisoning and procedural complications       
Facial bones fracture  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Femur fracture  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Hip fracture  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Joint injury  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Radiation necrosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Rib fracture  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Wound decomposition  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  2/256 (0.78%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Aspartate aminotransferase increased  1  1/256 (0.39%)  1 1/278 (0.36%)  1 2/277 (0.72%)  2
Blood bilirubin increased  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Blood corticotrophin decreased  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Blood prolactin increased  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Intraocular pressure decreased  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Liver function test abnormal  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  1/256 (0.39%)  1 1/278 (0.36%)  1 2/277 (0.72%)  2
Diabetic ketoacidosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Failure to thrive  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Gout  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypercalcaemia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Hypoalbuminaemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypokalaemia  1  0/256 (0.00%)  0 2/278 (0.72%)  2 1/277 (0.36%)  1
Hyponatraemia  1  1/256 (0.39%)  1 2/278 (0.72%)  2 2/277 (0.72%)  2
Metabolic disorder  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Tumour lysis syndrome  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Type 1 diabetes mellitus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Musculoskeletal and connective tissue disorders       
Back pain  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Intervertebral disc protrusion  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Muscular weakness  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Myalgia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pain in extremity  1  2/256 (0.78%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Pathological fracture  1  0/256 (0.00%)  0 2/278 (0.72%)  2 3/277 (1.08%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma gastric  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Basal cell carcinoma  1  0/256 (0.00%)  0 3/278 (1.08%)  5 3/277 (1.08%)  3
Basosquamous carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Bowen's disease  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Chronic lymphocytic leukaemia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Desmoplastic melanoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Gastrointestinal carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Intracranial tumour haemorrhage  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Lymphangiosis carcinomatosa  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Malignant melanoma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Metastases to central nervous system  1  3/256 (1.17%)  3 1/278 (0.36%)  1 1/277 (0.36%)  1
Metastatic malignant melanoma  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Neoplasm malignant  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Papillary thyroid cancer  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Papilloma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Squamous cell carcinoma  1  2/256 (0.78%)  2 4/278 (1.44%)  4 0/277 (0.00%)  0
Squamous cell carcinoma of skin  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Tumour haemorrhage  1  3/256 (1.17%)  3 0/278 (0.00%)  0 0/277 (0.00%)  0
Tumour pain  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Nervous system disorders       
Amnesia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Axonal neuropathy  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Brain oedema  1  1/256 (0.39%)  1 1/278 (0.36%)  1 0/277 (0.00%)  0
Cerebral haemorrhage  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Cerebral ischaemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cerebrovascular accident  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Dizziness  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Encephalopathy  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Epilepsy  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Guillain-Barre syndrome  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Haemorrhage intracranial  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Haemorrhagic stroke  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Horner's syndrome  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Hydrocephalus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Partial seizures  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Peripheral motor neuropathy  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Sciatica  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Seizure  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  3
Spinal cord compression  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Transient ischaemic attack  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Psychiatric disorders       
Completed suicide  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Confusional state  1  1/256 (0.39%)  1 0/278 (0.00%)  0 2/277 (0.72%)  2
Delirium  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Depression  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Dysphoria  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Mental status changes  1  1/256 (0.39%)  2 0/278 (0.00%)  0 0/277 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  1/256 (0.39%)  1 3/278 (1.08%)  3 3/277 (1.08%)  3
Hydronephrosis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Renal failure  1  2/256 (0.78%)  2 0/278 (0.00%)  0 4/277 (1.44%)  4
Tubulointerstitial nephritis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Urinary retention  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  0/256 (0.00%)  0 1/278 (0.36%)  2 0/277 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Cough  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Dyspnoea  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Haemoptysis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Hypoxia  1  1/256 (0.39%)  1 1/278 (0.36%)  1 0/277 (0.00%)  0
Lung disorder  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pleural effusion  1  1/256 (0.39%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Pneumonia aspiration  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pneumonitis  1  2/256 (0.78%)  2 2/278 (0.72%)  2 4/277 (1.44%)  4
Pneumothorax spontaneous  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pulmonary embolism  1  1/256 (0.39%)  1 1/278 (0.36%)  1 4/277 (1.44%)  4
Pulmonary thrombosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Skin and subcutaneous tissue disorders       
Drug eruption  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Lichen planus  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pemphigoid  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Rash  1  1/256 (0.39%)  1 1/278 (0.36%)  1 2/277 (0.72%)  2
Vascular disorders       
Aortic stenosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Arterial stenosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Arterial thrombosis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Deep vein thrombosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Haematoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypotension  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Lymphoedema  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Orthostatic hypotension  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Superior vena cava occlusion  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Thrombosis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Vein disorder  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Venous thrombosis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab 3 mg/kg Q3W Pembrolizumab 10 mg/kg Q2W Pembrolizumab 10 mg/kg Q3W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   228/256 (89.06%)      269/278 (96.76%)      254/277 (91.70%)    
Blood and lymphatic system disorders       
Anaemia  1  15/256 (5.86%)  20 30/278 (10.79%)  36 29/277 (10.47%)  31
Endocrine disorders       
Hyperthyroidism  1  7/256 (2.73%)  7 18/278 (6.47%)  20 11/277 (3.97%)  11
Hypothyroidism  1  6/256 (2.34%)  7 31/278 (11.15%)  31 28/277 (10.11%)  29
Gastrointestinal disorders       
Abdominal pain  1  24/256 (9.38%)  29 29/278 (10.43%)  36 20/277 (7.22%)  23
Abdominal pain upper  1  10/256 (3.91%)  12 15/278 (5.40%)  19 13/277 (4.69%)  14
Constipation  1  33/256 (12.89%)  37 52/278 (18.71%)  65 41/277 (14.80%)  47
Diarrhoea  1  76/256 (29.69%)  103 86/278 (30.94%)  141 77/277 (27.80%)  114
Dry mouth  1  1/256 (0.39%)  1 30/278 (10.79%)  31 23/277 (8.30%)  24
Nausea  1  61/256 (23.83%)  72 74/278 (26.62%)  87 68/277 (24.55%)  82
Vomiting  1  34/256 (13.28%)  38 41/278 (14.75%)  57 25/277 (9.03%)  29
General disorders       
Asthenia  1  38/256 (14.84%)  45 56/278 (20.14%)  103 49/277 (17.69%)  62
Chest pain  1  4/256 (1.56%)  4 15/278 (5.40%)  20 5/277 (1.81%)  5
Fatigue  1  82/256 (32.03%)  87 94/278 (33.81%)  123 95/277 (34.30%)  121
Influenza like illness  1  8/256 (3.13%)  9 17/278 (6.12%)  18 13/277 (4.69%)  21
Oedema peripheral  1  18/256 (7.03%)  20 27/278 (9.71%)  32 19/277 (6.86%)  20
Pyrexia  1  22/256 (8.59%)  24 38/278 (13.67%)  52 21/277 (7.58%)  30
Infections and infestations       
Nasopharyngitis  1  13/256 (5.08%)  13 30/278 (10.79%)  45 27/277 (9.75%)  31
Upper respiratory tract infection  1  14/256 (5.47%)  14 27/278 (9.71%)  31 16/277 (5.78%)  18
Urinary tract infection  1  12/256 (4.69%)  16 16/278 (5.76%)  23 14/277 (5.05%)  18
Investigations       
Alanine aminotransferase increased  1  14/256 (5.47%)  16 19/278 (6.83%)  26 16/277 (5.78%)  17
Aspartate aminotransferase increased  1  13/256 (5.08%)  15 22/278 (7.91%)  30 13/277 (4.69%)  19
Blood lactate dehydrogenase increased  1  8/256 (3.13%)  9 14/278 (5.04%)  20 4/277 (1.44%)  6
Weight decreased  1  13/256 (5.08%)  13 17/278 (6.12%)  18 21/277 (7.58%)  22
Metabolism and nutrition disorders       
Decreased appetite  1  42/256 (16.41%)  46 47/278 (16.91%)  60 55/277 (19.86%)  57
Hypertriglyceridaemia  1  2/256 (0.78%)  2 10/278 (3.60%)  14 14/277 (5.05%)  25
Hypokalaemia  1  6/256 (2.34%)  8 16/278 (5.76%)  26 14/277 (5.05%)  16
Musculoskeletal and connective tissue disorders       
Arthralgia  1  30/256 (11.72%)  32 58/278 (20.86%)  101 56/277 (20.22%)  59
Back pain  1  20/256 (7.81%)  20 46/278 (16.55%)  54 34/277 (12.27%)  37
Musculoskeletal pain  1  11/256 (4.30%)  13 23/278 (8.27%)  26 14/277 (5.05%)  14
Myalgia  1  12/256 (4.69%)  12 40/278 (14.39%)  52 22/277 (7.94%)  24
Neck pain  1  6/256 (2.34%)  6 14/278 (5.04%)  15 5/277 (1.81%)  5
Pain in extremity  1  16/256 (6.25%)  19 29/278 (10.43%)  35 19/277 (6.86%)  23
Nervous system disorders       
Dizziness  1  10/256 (3.91%)  11 28/278 (10.07%)  33 23/277 (8.30%)  27
Dysgeusia  1  7/256 (2.73%)  7 15/278 (5.40%)  21 6/277 (2.17%)  6
Headache  1  39/256 (15.23%)  42 52/278 (18.71%)  80 42/277 (15.16%)  61
Psychiatric disorders       
Anxiety  1  7/256 (2.73%)  7 15/278 (5.40%)  15 12/277 (4.33%)  12
Insomnia  1  16/256 (6.25%)  16 29/278 (10.43%)  32 27/277 (9.75%)  27
Respiratory, thoracic and mediastinal disorders       
Cough  1  24/256 (9.38%)  25 58/278 (20.86%)  77 52/277 (18.77%)  61
Dyspnoea  1  26/256 (10.16%)  28 32/278 (11.51%)  36 35/277 (12.64%)  35
Oropharyngeal pain  1  4/256 (1.56%)  4 17/278 (6.12%)  17 6/277 (2.17%)  6
Skin and subcutaneous tissue disorders       
Dry skin  1  8/256 (3.13%)  8 17/278 (6.12%)  19 15/277 (5.42%)  15
Erythema  1  10/256 (3.91%)  11 17/278 (6.12%)  22 9/277 (3.25%)  9
Pruritus  1  74/256 (28.91%)  90 66/278 (23.74%)  96 58/277 (20.94%)  73
Rash  1  43/256 (16.80%)  48 59/278 (21.22%)  87 57/277 (20.58%)  81
Rash maculo-papular  1  8/256 (3.13%)  8 16/278 (5.76%)  21 9/277 (3.25%)  11
Vitiligo  1  4/256 (1.56%)  4 32/278 (11.51%)  32 39/277 (14.08%)  41
Vascular disorders       
Hypertension  1  6/256 (2.34%)  6 17/278 (6.12%)  19 10/277 (3.61%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01866319     History of Changes
Other Study ID Numbers: 3475-006
2012-004907-10 ( EudraCT Number )
MK-3475-006 ( Other Identifier: Merck Protocol Number )
First Submitted: May 28, 2013
First Posted: May 31, 2013
Results First Submitted: December 9, 2015
Results First Posted: January 14, 2016
Last Update Posted: June 24, 2019