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Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)

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ClinicalTrials.gov Identifier: NCT03142334
Recruitment Status : Active, not recruiting
First Posted : May 5, 2017
Results First Posted : December 28, 2021
Last Update Posted : December 28, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Biological: Pembrolizumab
Drug: Placebo
Enrollment 994
Recruitment Details  
Pre-assignment Details Of the 994 participants randomized in the study, 984 participants received study medication and were evaluable for safety analyses (Database cutoff date 14 Dec 2020)
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year). Participants received placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
Period Title: Overall Study
Started 496 498
Treated 488 496
Continuing Study Treatment 0 1
Completed Study Treatment 298 365
Discontinued Study Treatment 190 130
Completed [1] 0 0
Not Completed 496 498
Reason Not Completed
Death             18             33
Withdrawal by Subject             15             11
Ongoing on trial follow up             463             454
[1]
Completed Trial
Arm/Group Title Pembrolizumab Placebo Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year). Participants received placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year). Total of all reporting groups
Overall Number of Baseline Participants 496 498 994
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 496 participants 498 participants 994 participants
58.3  (10.6) 58.6  (11.0) 58.4  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Female
149
  30.0%
139
  27.9%
288
  29.0%
Male
347
  70.0%
359
  72.1%
706
  71.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
Hispanic or Latino
72
  14.5%
62
  12.4%
134
  13.5%
Not Hispanic or Latino
381
  76.8%
394
  79.1%
775
  78.0%
Unknown or Not Reported
43
   8.7%
42
   8.4%
85
   8.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 498 participants 994 participants
American Indian or Alaska Native
10
   2.0%
2
   0.4%
12
   1.2%
Asian
63
  12.7%
75
  15.1%
138
  13.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
   1.4%
5
   1.0%
12
   1.2%
White
372
  75.0%
377
  75.7%
749
  75.4%
More than one race
8
   1.6%
5
   1.0%
13
   1.3%
Unknown or Not Reported
36
   7.3%
34
   6.8%
70
   7.0%
1.Primary Outcome
Title Disease-free Survival (DFS) as Assessed by the Investigator
Hide Description DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastasis status (M0 versus M1 no evidence of disease (NED) by investigator) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 versus 1), United States (US) participant (Yes versus No) within M0 group by investigator was used to report hazard ratio (HR) and 95% confidence intervals (CIs).
Time Frame Up to approximately 42 months (database cutoff date 14 Dec 2020)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
Participants received placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
Overall Number of Participants Analyzed 496 498
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = Median, lower and upper limit of 95% CIs for DFS was not reportable at the time of last disease assessment due to insufficient number of participants with events by the time of the data cutoff (14-Dec-2020).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments HR and the associated 95% CIs were calculated based on Cox Regression model and p-value was calculated based on log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Log Rank
Comments One-sided p-value was based on log-rank test stratified by metastasis status, ECOG PS, US participant within M0 group by investigator.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.53 to 0.87
Estimation Comments Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastasis status, ECOG PS, and US participant within M0 group by investigator was used to calculate HR and 95% CIs.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Participants are monitored for the occurrence of nonserious AEs for up to 30 days after last dose of study treatment and of serious AEs for up to 90 days after last dose of study treatment. The number of participants who experience an AE will be assessed.
Time Frame Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 13 months); Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 15 months)
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinue study treatment due to an AE will be assessed.
Time Frame Up to approximately 12 months
Outcome Measure Data Not Reported
5.Secondary Outcome
Title First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator
Hide Description DRSS1 is defined as the time from randomization to the first documented local recurrence of RCC as assessed by the investigator. For DRSS1, only local recurrence is counted as an event.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Second Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator
Hide Description DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or occurrence of distant kidney cancer metastasis(es) with visceral lesion, whichever occurs first, as assessed by the investigator.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR)
Hide Description EFS is defined as time from randomization to the first documented local recurrence or occurrence of distant kidney cancer metastasis(es) among participants which by BICR were considered disease-free at baseline (M0/M1 NED); or disease progression among participants which by BICR were considered to have baseline disease (M1), or death due to any cause, whichever occurs first.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
8.Secondary Outcome
Title DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator
Hide Description DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, or occurrence of distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. The PD-L1 expression status is based on combined positive score (CPS). If CPS is ≥ 1, PD-L1 expression status is positive and if the CPS is <1, PD-L1 expression status is negative.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
9.Secondary Outcome
Title OS According to Participant PD-L1 Expression Status (Positive, Negative)
Hide Description OS is defined as the time from randomization to death due to any cause. The PD-L1 expression status is based on combined positive score (CPS). If CPS is ≥ 1, PD-L1 expression status is positive and if the CPS is <1, PD-L1 expression status is negative.
Time Frame Up to approximately 72 months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score
Hide Description The QLQ-C30 quality of life (QOL) questionnaire contains 5 functioning scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain) and single symptom items (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Items are scored on a 4-point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much). The QLQC30 also contains 2 global health status scales that use 7-point scale scoring (1=very poor and 7=excellent). The change from baseline in the 2-item global health status/QOL life scale (range: 2-14) will be presented, with a higher score representing a higher QOL.
Time Frame Baseline and Week 52
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score
Hide Description The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. The change from baseline in the FKSI-DRS index score will be presented.
Time Frame Baseline and Week 52
Outcome Measure Data Not Reported
Time Frame Up to approximately 43 months (Database cutoff date 14 Dec 2020).
Adverse Event Reporting Description All-cause mortality was reported on all randomized participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment.
 
Arm/Group Title Pembrolizumab Placebo
Hide Arm/Group Description Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year). Participants received placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
All-Cause Mortality
Pembrolizumab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   18/496 (3.63%)      33/498 (6.63%)    
Hide Serious Adverse Events
Pembrolizumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   100/488 (20.49%)      56/496 (11.29%)    
Blood and lymphatic system disorders     
Thrombocytopenia  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Cardiac disorders     
Acute myocardial infarction  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Atrial fibrillation  1  2/488 (0.41%)  2 2/496 (0.40%)  2
Bundle branch block left  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Cardiac failure  1  2/488 (0.41%)  2 1/496 (0.20%)  1
Coronary artery stenosis  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Myocardial infarction  1  3/488 (0.61%)  3 0/496 (0.00%)  0
Myocarditis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Pleuropericarditis  1  1/488 (0.20%)  2 0/496 (0.00%)  0
Sinus node dysfunction  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Endocrine disorders     
Adrenal insufficiency  1  6/488 (1.23%)  6 0/496 (0.00%)  0
Autoimmune thyroiditis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Glucocorticoid deficiency  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Hyperthyroidism  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Hypophysitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Thyroiditis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Abdominal wall haematoma  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Colitis  1  5/488 (1.02%)  5 1/496 (0.20%)  1
Diarrhoea  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Diverticulum  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Enterocolitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Gastrointestinal haemorrhage  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Gastrooesophageal reflux disease  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Large intestine polyp  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Mallory-Weiss syndrome  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Small intestinal obstruction  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Vomiting  1  2/488 (0.41%)  2 0/496 (0.00%)  0
General disorders     
Influenza like illness  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Multiple organ dysfunction syndrome  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Pyrexia  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Hepatobiliary disorders     
Cholecystitis  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Cholestasis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Hepatitis  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Hepatitis alcoholic  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Immune-mediated hepatitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Infections and infestations     
Anorectal infection  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Appendicitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Bronchitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Campylobacter infection  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Device related infection  1  0/488 (0.00%)  0 1/496 (0.20%)  2
Encephalitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Helicobacter infection  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Infected lymphocele  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Infection  1  1/488 (0.20%)  2 0/496 (0.00%)  0
Influenza  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Intervertebral discitis  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Lower respiratory tract infection  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Meningitis aseptic  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Pneumonia  1  6/488 (1.23%)  6 1/496 (0.20%)  1
Pneumonia influenzal  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Pyelonephritis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Rectal abscess  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Respiratory tract infection  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Sepsis  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Septic shock  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Urinary tract infection  1  1/488 (0.20%)  1 2/496 (0.40%)  2
Vascular device infection  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Viral infection  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Wound infection  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Injury, poisoning and procedural complications     
Accidental overdose  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Ankle fracture  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Craniocerebral injury  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Foot fracture  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Incisional hernia  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Infusion related reaction  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Joint dislocation  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Multiple injuries  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Nail injury  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Post procedural haematuria  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Tendon rupture  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Diabetes mellitus  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Diabetic ketoacidosis  1  5/488 (1.02%)  6 0/496 (0.00%)  0
Glucose tolerance impaired  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Hyperamylasaemia  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Hypokalaemia  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Hyponatraemia  1  2/488 (0.41%)  2 1/496 (0.20%)  1
Type 1 diabetes mellitus  1  4/488 (0.82%)  4 0/496 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Back pain  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Chondrocalcinosis pyrophosphate  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Musculoskeletal chest pain  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Osteoarthritis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Pathological fracture  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Sjogren's syndrome  1  2/488 (0.41%)  2 0/496 (0.00%)  0
Trigger finger  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/488 (0.00%)  0 3/496 (0.60%)  3
Basal cell carcinoma metastatic  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Benign lung neoplasm  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Choroid melanoma  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Colon neoplasm  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Neuroendocrine tumour  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Papillary thyroid cancer  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Primary myelofibrosis  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Prostate cancer  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Transitional cell carcinoma  1  1/488 (0.20%)  1 2/496 (0.40%)  2
Nervous system disorders     
Ataxia  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Cerebellar ischaemia  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Cerebellar syndrome  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Cerebral infarction  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Cerebral ischaemia  1  1/488 (0.20%)  2 0/496 (0.00%)  0
Cognitive disorder  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Facial paralysis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Haemorrhage intracranial  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Ischaemic stroke  1  0/488 (0.00%)  0 2/496 (0.40%)  2
Loss of consciousness  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Myasthenic syndrome  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Syncope  1  0/488 (0.00%)  0 2/496 (0.40%)  2
Tension headache  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Transient global amnesia  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Psychiatric disorders     
Depression  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Suicide attempt  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Renal and urinary disorders     
Acute kidney injury  1  6/488 (1.23%)  6 0/496 (0.00%)  0
Bladder mass  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Calculus urinary  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Nephrolithiasis  1  0/488 (0.00%)  0 2/496 (0.40%)  3
Renal colic  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Renal pain  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Tubulointerstitial nephritis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Urinary retention  1  1/488 (0.20%)  1 2/496 (0.40%)  2
Reproductive system and breast disorders     
Testicular torsion  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Uterine polyp  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Immune-mediated pneumonitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Interstitial lung disease  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Pleural effusion  1  1/488 (0.20%)  1 1/496 (0.20%)  1
Pneumonitis  1  3/488 (0.61%)  3 0/496 (0.00%)  0
Pulmonary embolism  1  1/488 (0.20%)  1 3/496 (0.60%)  3
Skin and subcutaneous tissue disorders     
Lichenification  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Rash maculo-papular  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Stevens-Johnson syndrome  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Essential hypertension  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Giant cell arteritis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Haematoma  1  0/488 (0.00%)  0 1/496 (0.20%)  1
Orthostatic hypotension  1  1/488 (0.20%)  1 0/496 (0.00%)  0
Vasculitis  1  1/488 (0.20%)  1 0/496 (0.00%)  0
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
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   436/488 (89.34%)      393/496 (79.23%)    
Endocrine disorders     
Hyperthyroidism  1  56/488 (11.48%)  58 1/496 (0.20%)  1
Hypothyroidism  1  103/488 (21.11%)  111 18/496 (3.63%)  20
Gastrointestinal disorders     
Abdominal pain  1  36/488 (7.38%)  54 39/496 (7.86%)  50
Constipation  1  35/488 (7.17%)  39 40/496 (8.06%)  42
Diarrhoea  1  123/488 (25.20%)  195 111/496 (22.38%)  171
Dry mouth  1  33/488 (6.76%)  37 5/496 (1.01%)  5
Nausea  1  80/488 (16.39%)  105 48/496 (9.68%)  61
Vomiting  1  39/488 (7.99%)  44 28/496 (5.65%)  31
General disorders     
Asthenia  1  50/488 (10.25%)  85 36/496 (7.26%)  50
Fatigue  1  145/488 (29.71%)  180 120/496 (24.19%)  156
Influenza like illness  1  25/488 (5.12%)  26 21/496 (4.23%)  24
Oedema peripheral  1  21/488 (4.30%)  26 27/496 (5.44%)  30
Pyrexia  1  31/488 (6.35%)  31 22/496 (4.44%)  24
Infections and infestations     
Nasopharyngitis  1  28/488 (5.74%)  33 42/496 (8.47%)  47
Upper respiratory tract infection  1  27/488 (5.53%)  32 24/496 (4.84%)  27
Urinary tract infection  1  29/488 (5.94%)  36 20/496 (4.03%)  30
Investigations     
Alanine aminotransferase increased  1  35/488 (7.17%)  42 17/496 (3.43%)  23
Aspartate aminotransferase increased  1  36/488 (7.38%)  40 10/496 (2.02%)  14
Blood creatinine increased  1  50/488 (10.25%)  59 42/496 (8.47%)  52
Metabolism and nutrition disorders     
Decreased appetite  1  34/488 (6.97%)  34 10/496 (2.02%)  10
Hyperglycaemia  1  28/488 (5.74%)  36 17/496 (3.43%)  20
Musculoskeletal and connective tissue disorders     
Arthralgia  1  108/488 (22.13%)  159 93/496 (18.75%)  123
Back pain  1  49/488 (10.04%)  56 63/496 (12.70%)  70
Myalgia  1  46/488 (9.43%)  60 32/496 (6.45%)  38
Pain in extremity  1  35/488 (7.17%)  41 25/496 (5.04%)  30
Nervous system disorders     
Dizziness  1  39/488 (7.99%)  47 27/496 (5.44%)  32
Headache  1  69/488 (14.14%)  92 62/496 (12.50%)  91
Psychiatric disorders     
Insomnia  1  26/488 (5.33%)  27 29/496 (5.85%)  32
Respiratory, thoracic and mediastinal disorders     
Cough  1  76/488 (15.57%)  90 50/496 (10.08%)  56
Dyspnoea  1  30/488 (6.15%)  32 27/496 (5.44%)  38
Skin and subcutaneous tissue disorders     
Dry skin  1  26/488 (5.33%)  30 22/496 (4.44%)  22
Pruritus  1  111/488 (22.75%)  148 65/496 (13.10%)  75
Rash  1  98/488 (20.08%)  151 53/496 (10.69%)  83
Vascular disorders     
Hypertension  1  38/488 (7.79%)  46 39/496 (7.86%)  43
1
Term from vocabulary, MedDRA 23.1
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.
The investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect proprietary information and to provide comments.
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 LLC
ClinicalTrials.gov Identifier: NCT03142334    
Other Study ID Numbers: 3475-564
2016-004351-75 ( EudraCT Number )
173704 ( Registry Identifier: JAPAC-CTI )
MK-3475-564 ( Other Identifier: Merck )
KEYNOTE-564 ( Other Identifier: Merck )
First Submitted: May 3, 2017
First Posted: May 5, 2017
Results First Submitted: November 29, 2021
Results First Posted: December 28, 2021
Last Update Posted: December 28, 2021