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Trial record 78 of 519 for:    melanoma phase III

Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/1325-MG/KEYNOTE-054)

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: NCT02362594
Recruitment Status : Active, not recruiting
First Posted : February 13, 2015
Results First Posted : January 4, 2019
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
European Organisation for Research and Treatment of Cancer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Melanoma
Interventions Biological: pembrolizumab
Drug: placebo
Enrollment 1019
Recruitment Details  
Pre-assignment Details As of the 02-Oct-2017 interim database cut-off date, of the 1019 randomized participants in Part 1, 544 had completed Part 1 and 62 were continuing in Part 1. This interim results disclosure is for Part 1 only.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description In Part 1, participants received pembrolizumab 200 mg intravenously (IV) as post-surgery therapy every 3 weeks (Q3W) for up to 1 year. In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Period Title: Overall Study
Started 514 505
Treated 509 502
Continuing Part 1 Adjuvant Therapy 41 21
Completed [1] 264 280
Not Completed 250 225
[1]
Completed Part 1 Adjuvant Therapy
Arm/Group Title Pembrolizumab Placebo Total
Hide Arm/Group Description In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year. In Part 1, participants received placebo IV as post-surgery therapy Q3W. Total of all reporting groups
Overall Number of Baseline Participants 514 505 1019
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 514 participants 505 participants 1019 participants
53.9  (13.6) 53.7  (14.2) 53.8  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 514 participants 505 participants 1019 participants
Female
190
  37.0%
201
  39.8%
391
  38.4%
Male
324
  63.0%
304
  60.2%
628
  61.6%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Programmed Death-Ligand 1 (PD-L1) Tumor Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
PD-L1 Positive Number Analyzed 514 participants 505 participants 1019 participants
428
  83.3%
425
  84.2%
853
  83.7%
PD-L1 Negative Number Analyzed 514 participants 505 participants 1019 participants
59
  11.5%
57
  11.3%
116
  11.4%
Undetermined Number Analyzed 514 participants 505 participants 1019 participants
27
   5.3%
23
   4.6%
50
   4.9%
[1]
Measure Description: Tumor PD-L1 status was assessed by immunohistochemistry (IHC) and recorded as positive (≥1% PD-L1 IHC), negative (<1% PD-L1 IHC), or undetermined level of expression (indeterminate PD-L1 IHC).
Melanoma Stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Stage IIIA (> 1 mm) Number Analyzed 514 participants 505 participants 1019 participants
80
  15.6%
80
  15.8%
160
  15.7%
Stage IIIB Number Analyzed 514 participants 505 participants 1019 participants
237
  46.1%
230
  45.5%
467
  45.8%
Stage IIIC (1-3 LN+) Number Analyzed 514 participants 505 participants 1019 participants
95
  18.5%
93
  18.4%
188
  18.4%
Stage IIIC (≥4 LN+) Number Analyzed 514 participants 505 participants 1019 participants
102
  19.8%
102
  20.2%
204
  20.0%
[1]
Measure Description: Participants were stratified by melanoma stage using the American Joint Committee on Cancer (AJCC) 7th edition stage as follows: Stage IIIA (with >1 mm metastasis), Stage IIIB, Stage IIIC with 1-3 positive lymph nodes (LN+), and Stage IIIC with ≥4 LN+.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 514 participants 505 participants 1019 participants
North America
38
   7.4%
37
   7.3%
75
   7.4%
Europe
341
  66.3%
336
  66.5%
677
  66.4%
Australia/New Zealand
111
  21.6%
112
  22.2%
223
  21.9%
Other
24
   4.7%
20
   4.0%
44
   4.3%
1.Primary Outcome
Title Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants
Hide Description RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants in both treatment arms of Part 1.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 514 505
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
82.2
(78.6 to 85.3)
73.3
(69.2 to 77.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Placebo
Comments Comparison of RFS time-to-event distribution between the 2 treatment arms was based on Cox regression model with treatment as a covariate stratified by stage (IIIA [>1 mm metastasis] vs. IIIB vs. IIIC 1-3 nodes vs. IIIC ≥4 nodes) as indicated at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments One-sided p-value based on log-rank test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 98.4%
0.43 to 0.74
Estimation Comments [Not Specified]
2.Primary Outcome
Title Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among Participants With PD-L1-positive Tumor Expression
Hide Description RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants with PD-L1-positive tumors in both treatment arms of Part 1.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 with PD-L1-positive tumors.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 428 425
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
83.8
(80.0 to 87.0)
75.4
(71.0 to 79.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Placebo
Comments Comparison of RFS time-to-event distribution between the 2 treatment arms (PD-L1-positive participants) was based on Cox regression model with treatment as a covariate stratified by stage (IIIA [>1 mm metastasis] vs. IIIB vs. IIIC 1-3 nodes vs. IIIC ≥4 nodes) as indicated at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments One-sided p-value based on log-rank test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95.0%
0.42 to 0.69
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Distant Metastases-free Survival (DMFS) in All Participants
Hide Description DMFS will be defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. For participants who remain alive and distant metastasis-free, DMFS will be censored on the date of last visit/contact with disease assessments. The percentage of participants with DMFS will be reported for all participants in both treatment arms.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Distant Metastases-free Survival (DMFS) for Participants With PD-L1-positive Tumor Expression
Hide Description

Description:

DMFS will be defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. For participants who remain alive and distant metastasis-free, DMFS will be censored on the date of last visit/contact with disease assessments. The percentage of participants with DMFS will be reported for all participants with PD-L1-positive tumors in both treatment arms.

Time Frame Up to 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Overall Survival (OS) for All Participants
Hide Description OS will be defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of participants still alive will be censored at the moment of last visit/contact. OS will be reported for all participants in both treatment arms.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Overall Survival (OS) for Participants With PD-L1-positive Tumor Expression
Hide Description OS will be defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of participants still alive will be censored at the moment of last visit/contact. OS will be reported for all participants with PD-L1-positive tumors in both treatment arms.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Number of Participants Who Experienced At Least 1 Adverse Event (AE)
Hide Description An AE is defined as “any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment”. An AE can therefore be any unfavorable and unintended signs (such as rash or enlarged liver), symptoms (such as nausea or chest pain), an abnormal laboratory finding (including results of blood tests, x-rays or scans) or a disease temporarily associated with the use of the protocol treatment, whether or not considered related to the investigational medicinal product. The number of participants who experienced at least 1 AE was reported for all participants in each treatment arm.
Time Frame Up to 22 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 509 502
Measure Type: Count of Participants
Unit of Measure: Participants
475
  93.3%
453
  90.2%
8.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Hide Description An AE is defined as “any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment”. An AE can therefore be any unfavorable and unintended signs (such as rash or enlarged liver), symptoms (such as nausea or chest pain), an abnormal laboratory finding (including results of blood tests, x-rays or scans) or a disease temporarily associated with the use of the protocol treatment, whether or not considered related to the investigational medicinal product. The number of participants who discontinued study treatment due to an AE was reported for all participants in each treatment arm.
Time Frame Up to 22 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 509 502
Measure Type: Count of Participants
Unit of Measure: Participants
70
  13.8%
18
   3.6%
9.Secondary Outcome
Title Clearance (CL) of Pembrolizumab
Hide Description Blood samples were to be collected at pre-specified time points and plasma isolated for analysis of pembrolizumab CL, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following IV pembrolizumab administration. Samples were not collected and this analysis was not performed.
Time Frame Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
As pre-specified by the protocol, pembrolizumab CL was not analyzed as planned and no data were collected since by the time of the interim analysis, pembrolizumab pharmacokinetics (PK) in melanoma patients had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Volume of Distribution (V) of Pembrolizumab
Hide Description Blood samples were to be collected at pre-specified time points and plasma isolated for analysis of pembrolizumab V, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. Samples were not collected and this analysis was not performed.
Time Frame Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
As pre-specified by the protocol, pembrolizumab V was not analyzed as planned and no data were collected since by the time of the interim analysis, pembrolizumab PK in melanoma patients had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Number of Participants Positive for Anti-Drug Antibodies (ADA) After Pembrolizumab Treatment
Hide Description Pre- and post-baseline serum samples from participants treated with pembrolizumab were analyzed for ADA by means of a neutralizing antibody assay which assessed the ability of ADA to block (neutralize) binding of pembrolizumab to Programmed Cell Death-1 (PD-1) protein. Overall immunogenicity was defined as the number of treatment emergent positive participants based on the total number of evaluable participants (treatment emergent positive, non-treatment emergent positive and negative immunogenicity status).
Time Frame Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who had at least one ADA sample available after treatment with pembrolizumab and who had treatment emergent positive, non-treatment emergent positive, or negative immunogenicity status. Participants receiving Placebo treatment in Part 1 were not analyzed for ADA.
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year.
In Part 1, participants received placebo IV as post-surgery therapy Q3W.
Overall Number of Participants Analyzed 495 0
Measure Type: Count of Participants
Unit of Measure: Participants
Negative
473
  95.6%
Non-Treatment emergent positive
5
   1.0%
Treatment emergent positive
17
   3.4%
Time Frame Up to 29 months (through database cut-off date of 02-Oct-2017)
Adverse Event Reporting Description

All-Cause Mortality was reported for all randomized participants in Part 1.

Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment in Part 1. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

 
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description In Part 1, participants received pembrolizumab 200 mg IV as post-surgery therapy Q3W for up to 1 year. In Part 1, participants received placebo IV as post-surgery therapy Q3W.
All-Cause Mortality
Pembrolizumab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   25/514 (4.86%)      35/505 (6.93%)    
Show Serious Adverse Events Hide Serious Adverse Events
Pembrolizumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   128/509 (25.15%)      82/502 (16.33%)    
Cardiac disorders     
Acute myocardial infarction  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Atrial fibrillation  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Autoimmune pericarditis  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Cardiac failure congestive  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Myocarditis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Ventricular tachycardia  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Endocrine disorders     
Adrenocortical insufficiency acute  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Hyperthyroidism  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Hypophysitis  1  3/509 (0.59%)  3 0/502 (0.00%)  0
Hypopituitarism  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Secondary adrenocortical insufficiency  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Thyroiditis  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Eye disorders     
Conjunctivitis allergic  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Abdominal pain upper  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Aptyalism  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Autoimmune colitis  1  3/509 (0.59%)  6 0/502 (0.00%)  0
Colitis  1  8/509 (1.57%)  11 0/502 (0.00%)  0
Constipation  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Diarrhoea  1  5/509 (0.98%)  9 2/502 (0.40%)  2
Enteritis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Food poisoning  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Gastritis  1  2/509 (0.39%)  3 0/502 (0.00%)  0
Haemorrhoids  1  0/509 (0.00%)  0 1/502 (0.20%)  3
Ileus  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Large intestine perforation  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Nausea  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Oesophageal haemorrhage  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Oral lichen planus  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Pancreatitis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Pancreatitis acute  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Small intestinal perforation  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Vomiting  1  1/509 (0.20%)  1 1/502 (0.20%)  1
General disorders     
Discomfort  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Fatigue  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Granuloma  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Oedema  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Papillitis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Pyrexia  1  4/509 (0.79%)  8 0/502 (0.00%)  0
Systemic inflammatory response syndrome  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Hepatobiliary disorders     
Autoimmune hepatitis  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Cholecystitis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Cholelithiasis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Hepatitis  1  2/509 (0.39%)  8 0/502 (0.00%)  0
Immune system disorders     
Anaphylactic reaction  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Sarcoidosis  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Infections and infestations     
Bronchitis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Cellulitis  1  3/509 (0.59%)  4 7/502 (1.39%)  8
Cholecystitis infective  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Diverticulitis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Erysipelas  1  2/509 (0.39%)  2 4/502 (0.80%)  4
Gastroenteritis viral  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Infected seroma  1  0/509 (0.00%)  0 2/502 (0.40%)  2
Infection  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Lung infection  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Pneumonia  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Post procedural cellulitis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Respiratory tract infection viral  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Skin infection  1  1/509 (0.20%)  1 1/502 (0.20%)  1
Soft tissue infection  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Subcutaneous abscess  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Upper respiratory tract infection  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Viral infection  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Vulvitis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Injury, poisoning and procedural complications     
Animal bite  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Post procedural haematoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Spinal column injury  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Subarachnoid haemorrhage  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Synovial rupture  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Wound necrosis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  2/509 (0.39%)  3 0/502 (0.00%)  0
Aspartate aminotransferase increased  1  3/509 (0.59%)  4 0/502 (0.00%)  0
Gamma-glutamyltransferase increased  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Diabetic ketoacidosis  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Hypercreatininaemia  1  1/509 (0.20%)  4 0/502 (0.00%)  0
Hyperglycaemia  1  2/509 (0.39%)  5 0/502 (0.00%)  0
Hyponatraemia  1  1/509 (0.20%)  2 2/502 (0.40%)  3
Type 1 diabetes mellitus  1  3/509 (0.59%)  5 0/502 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Fasciitis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Intervertebral disc protrusion  1  1/509 (0.20%)  3 2/502 (0.40%)  2
Myositis  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Rheumatoid arthritis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenoma benign  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Angiolipoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Basal cell carcinoma  1  17/509 (3.34%)  24 25/502 (4.98%)  36
Benign lymph node neoplasm  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Benign neoplasm of testis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Bowen's disease  1  4/509 (0.79%)  4 1/502 (0.20%)  1
Choroid melanoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Hepatocellular carcinoma  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Intracranial tumour haemorrhage  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Invasive ductal breast carcinoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Keratoacanthoma  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Lentigo maligna  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Leydig cell tumour of the testis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Malignant melanoma  1  3/509 (0.59%)  3 3/502 (0.60%)  4
Malignant melanoma in situ  1  1/509 (0.20%)  1 6/502 (1.20%)  6
Mantle cell lymphoma  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Melanocytic naevus  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Meningioma  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Metastases to central nervous system  1  1/509 (0.20%)  1 1/502 (0.20%)  1
Nodular melanoma  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Prostate cancer  1  1/509 (0.20%)  1 1/502 (0.20%)  1
Rectal adenocarcinoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Renal cell carcinoma  1  1/509 (0.20%)  1 1/502 (0.20%)  1
Squamous cell carcinoma  1  6/509 (1.18%)  10 3/502 (0.60%)  4
Squamous cell carcinoma of skin  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Superficial spreading melanoma stage unspecified  1  0/509 (0.00%)  0 1/502 (0.20%)  2
Thyroid cancer  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Nervous system disorders     
Carotid artery aneurysm  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Cerebrovascular accident  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Dizziness  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Facial paralysis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Headache  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Myasthenia gravis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Peripheral sensory neuropathy  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Sciatica  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Transient ischaemic attack  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Psychiatric disorders     
Anxiety  1  1/509 (0.20%)  1 1/502 (0.20%)  1
Renal and urinary disorders     
Acute kidney injury  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Autoimmune nephritis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Glomerulosclerosis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Nephritis  1  0/509 (0.00%)  0 1/502 (0.20%)  4
Nephrolithiasis  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Renal colic  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Tubulointerstitial nephritis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Urinary retention  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Interstitial lung disease  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Pleural effusion  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Pneumonitis  1  7/509 (1.38%)  8 0/502 (0.00%)  0
Pneumothorax  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Pulmonary embolism  1  2/509 (0.39%)  2 0/502 (0.00%)  0
Skin and subcutaneous tissue disorders     
Drug reaction with eosinophilia and systemic symptoms  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Lichenoid keratosis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Psoriasis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Rash  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Rash maculo-papular  1  1/509 (0.20%)  3 0/502 (0.00%)  0
Urticaria  1  1/509 (0.20%)  2 0/502 (0.00%)  0
Surgical and medical procedures     
Appendicectomy  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Haematoma  1  0/509 (0.00%)  0 1/502 (0.20%)  1
Hypotension  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Lymphoedema  1  1/509 (0.20%)  1 0/502 (0.00%)  0
Venous thrombosis  1  0/509 (0.00%)  0 1/502 (0.20%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   443/509 (87.03%)      409/502 (81.47%)    
Endocrine disorders     
Hyperthyroidism  1  52/509 (10.22%)  61 6/502 (1.20%)  6
Hypothyroidism  1  75/509 (14.73%)  93 14/502 (2.79%)  14
Gastrointestinal disorders     
Abdominal pain  1  37/509 (7.27%)  40 31/502 (6.18%)  37
Constipation  1  34/509 (6.68%)  37 29/502 (5.78%)  32
Diarrhoea  1  140/509 (27.50%)  238 129/502 (25.70%)  234
Dry mouth  1  30/509 (5.89%)  32 10/502 (1.99%)  10
Nausea  1  88/509 (17.29%)  112 73/502 (14.54%)  103
Vomiting  1  40/509 (7.86%)  55 22/502 (4.38%)  25
General disorders     
Asthenia  1  56/509 (11.00%)  93 42/502 (8.37%)  71
Fatigue  1  168/509 (33.01%)  247 168/502 (33.47%)  232
Influenza like illness  1  55/509 (10.81%)  73 38/502 (7.57%)  47
Infections and infestations     
Nasopharyngitis  1  44/509 (8.64%)  54 25/502 (4.98%)  26
Upper respiratory tract infection  1  39/509 (7.66%)  49 30/502 (5.98%)  39
Investigations     
Alanine aminotransferase increased  1  35/509 (6.88%)  41 24/502 (4.78%)  30
Weight decreased  1  55/509 (10.81%)  69 39/502 (7.77%)  64
Weight increased  1  63/509 (12.38%)  96 82/502 (16.33%)  117
Metabolism and nutrition disorders     
Decreased appetite  1  36/509 (7.07%)  40 13/502 (2.59%)  15
Musculoskeletal and connective tissue disorders     
Arthralgia  1  79/509 (15.52%)  130 72/502 (14.34%)  98
Back pain  1  34/509 (6.68%)  37 54/502 (10.76%)  69
Myalgia  1  35/509 (6.88%)  40 25/502 (4.98%)  29
Pain in extremity  1  22/509 (4.32%)  26 30/502 (5.98%)  34
Nervous system disorders     
Dizziness  1  26/509 (5.11%)  29 31/502 (6.18%)  38
Headache  1  95/509 (18.66%)  135 93/502 (18.53%)  126
Respiratory, thoracic and mediastinal disorders     
Cough  1  70/509 (13.75%)  88 55/502 (10.96%)  66
Dyspnoea  1  46/509 (9.04%)  50 25/502 (4.98%)  26
Skin and subcutaneous tissue disorders     
Pruritus  1  99/509 (19.45%)  138 58/502 (11.55%)  74
Rash  1  67/509 (13.16%)  90 43/502 (8.57%)  51
Rash maculo-papular  1  27/509 (5.30%)  44 24/502 (4.78%)  26
Vascular disorders     
Hypertension  1  74/509 (14.54%)  178 77/502 (15.34%)  209
Lymphoedema  1  26/509 (5.11%)  28 36/502 (7.17%)  37
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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.
All draft publications, including abstracts or detailed summaries of any proposed presentations, must be submitted to the Sponsor at the earliest practicable time for review, not less than 30 days before submission or presentation unless otherwise set forth in the clinical trial agreement. Sponsor shall have the right to delete any confidential information contained in any proposed presentation or abstract and may delay publication for up to 60 days for purposes of filing a patent application.
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
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02362594     History of Changes
Other Study ID Numbers: 3475-054
1325-MG ( Other Identifier: European Organisation for Research and Treatment of Cancer )
2014-004944-37 ( EudraCT Number )
163277 ( Registry Identifier: JAPIC-CTI )
KEYNOTE-054 ( Other Identifier: Merck )
MK-3475-054 ( Other Identifier: Merck )
First Submitted: February 9, 2015
First Posted: February 13, 2015
Results First Submitted: December 10, 2018
Results First Posted: January 4, 2019
Last Update Posted: February 12, 2019