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)

• ClinicalTrials.gov Identifier: NCT03142334
• Recruitment Status: Active, not recruiting
• First Posted: May 5, 2017
• Results First Posted: December 28, 2021
• Last Update Posted: June 29, 2023
• Sponsor: Merck Sharp & Dohme LLC
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Pembrolizumab	Placebo	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS) as Assessed by the Investigator
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)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Pembrolizumab	Placebo
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).

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)
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)
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
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
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
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)
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
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)
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
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
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

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• 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):

Powles T, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, Hajek J, Gurney H, Chang YH, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Burgents JE, Xu L, Imai K, Quinn DI, Choueiri TK; KEYNOTE-564 Investigators. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1133-1144. doi: 10.1016/S1470-2045(22)00487-9. Erratum In: Lancet Oncol. 2023 Jan;24(1):e10.

Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694. doi: 10.1056/NEJMoa2106391.

Marconi L, Sun M, Beisland C, Klatte T, Ljungberg B, Stewart GD, Dabestani S, Choueiri TK, Bex A. Prevalence, Disease-free, and Overall Survival of Contemporary Patients With Renal Cell Carcinoma Eligible for Adjuvant Checkpoint Inhibitor Trials. Clin Genitourin Cancer. 2021 Apr;19(2):e92-e99. doi: 10.1016/j.clgc.2020.12.005. Epub 2021 Jan 7.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03142334
• Other Study ID Numbers: 3475-564; 173704 ( Registry Identifier: JAPAC-CTI ); MK-3475-564 ( Other Identifier: Merck ); KEYNOTE-564 ( Other Identifier: Merck ); 2016-004351-75 ( EudraCT Number )
• 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: June 29, 2023