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Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)

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ClinicalTrials.gov Identifier: NCT02853331
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Results First Posted : November 8, 2019
Last Update Posted : March 7, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Biological: Pembrolizumab
Drug: Axitinib
Drug: Sunitinib
Enrollment 861
Recruitment Details  
Pre-assignment Details These interim results are based on a database cutoff date of 24-Aug-2018, at which time 693 participants were ongoing in the study.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily. Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Period Title: Overall Study
Started 432 429
Treated 429 425
Completed 0 0
Not Completed 432 429
Reason Not Completed
Death             59             95
Withdrawal by Subject             5             9
Ongoing in study             368             325
Arm/Group Title Pembrolizumab + Axitinib Sunitinib Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily. Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks. Total of all reporting groups
Overall Number of Baseline Participants 432 429 861
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 432 participants 429 participants 861 participants
61.2  (10.0) 60.8  (10.2) 61.0  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 432 participants 429 participants 861 participants
Female
124
  28.7%
109
  25.4%
233
  27.1%
Male
308
  71.3%
320
  74.6%
628
  72.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 432 participants 429 participants 861 participants
Hispanic or Latino
19
   4.4%
18
   4.2%
37
   4.3%
Not Hispanic or Latino
377
  87.3%
387
  90.2%
764
  88.7%
Unknown or Not Reported
36
   8.3%
24
   5.6%
60
   7.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 432 participants 429 participants 861 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
66
  15.3%
71
  16.6%
137
  15.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
10
   2.3%
8
   1.9%
18
   2.1%
White
343
  79.4%
341
  79.5%
684
  79.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
13
   3.0%
9
   2.1%
22
   2.6%
International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Risk Group   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 432 participants 429 participants 861 participants
Favorable
138
  31.9%
131
  30.5%
269
  31.2%
Intermediate
238
  55.1%
246
  57.3%
484
  56.2%
Poor
56
  13.0%
52
  12.1%
108
  12.5%
[1]
Measure Description: Participants were stratified by IMDC risk group using the following criteria: baseline Karnofsky Performance Status <80%; interval between initial diagnosis of renal cell carcinoma to start of first-line systemic treatment for advanced disease <1year; baseline hemoglobin <lower limit of normal (LLN); baseline platelet count >upper limit of normal (ULN); baseline corrected calcium1 >ULN; and baseline neutrophil >ULN. The category was determined by totaling the risk factors per participant and scored as favorable (no factors); intermediate (1 or 2 factors); and poor (≥3 factors).
Geographic Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 432 participants 429 participants 861 participants
North America
104
  24.1%
103
  24.0%
207
  24.0%
Western Europe
106
  24.5%
104
  24.2%
210
  24.4%
Rest of World
222
  51.4%
222
  51.7%
444
  51.6%
[1]
Measure Description: Participants were stratified by geographic region using the following categories: North America; Western Europe; and Rest of the World.
1.Primary Outcome
Title Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Median (95% Confidence Interval)
Unit of Measure: Months
15.1
(12.6 to 17.7)
11.0
(8.7 to 12.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Axitinib, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00012
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.56 to 0.84
Estimation Comments HR based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by IMDC risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World).
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The OS for participants is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
OS median, OS lower limit & OS upper limit were not reached by the time of the data cutoff (24-Aug-2018).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Axitinib, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00005
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.38 to 0.74
Estimation Comments HR based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by IMDC risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World).
3.Secondary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
Hide Description ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR was calculated using the Miettinen & Nurminen method stratified by International Metastatic Renal Cell Carcinoma (RCC) Database Consortium (IMDC) risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World). The percentage of participants who experienced a CR or PR is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
59.3
(54.5 to 63.9)
35.7
(31.1 to 40.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Axitinib, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments H0: difference in %=0 versus H1: difference in % >0
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 23.6
Confidence Interval (2-Sided) 95%
17.2 to 29.9
Estimation Comments Difference in percentages based on Miettinen & Nurminen method stratified by IMDC risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World).
4.Secondary Outcome
Title Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
Hide Description DCR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions), Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), or Stable Disease (SD) per RECIST 1.1 for ≥6 months. The DCR was calculated using the Miettinen & Nurminen method stratified by International Metastatic Renal Cell Carcinoma (RCC) Database Consortium (IMDC) risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World). The percentage of participants who experienced a CR, PR, or SD is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who experienced a PR, CR or SD for ≥6 months.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
71.5
(67.0 to 75.7)
60.6
(55.8 to 65.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Axitinib, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 11.0
Confidence Interval (2-Sided) 95%
4.8 to 17.0
Estimation Comments Difference in percentages based on Miettinen & Nurminen method stratified by IMDC risk group (favorable vs. intermediate vs. poor) and geographic region (North America vs. Western Europe vs. Rest of World).
5.Secondary Outcome
Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
Hide Description DOR was defined as the time from first documented evidence of a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 until progressive disease (PD) or death due to any cause, whichever occurred first. PD was defined per RECIST 1.1 as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. The DOR for all participants who experienced a CR or PR is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who experienced a CR or PR.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 256 153
Median (Full Range)
Unit of Measure: Months
NA [1] 
(1.4 to NA)
15.2 [2] 
(1.1 to NA)
[1]
Median DOR not reached by the time of the data cutoff (24-Aug-2018). DOR upper limit not calculated due to no progressive disease by the time of last disease assessment.
[2]
DOR upper limit not calculated due to no progressive disease by the time of last disease assessment.
6.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 429 425
Measure Type: Count of Participants
Unit of Measure: Participants
422
  98.4%
423
  99.5%
7.Secondary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 429 425
Measure Type: Count of Participants
Unit of Measure: Participants
131
  30.5%
59
  13.9%
8.Secondary Outcome
Title Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants
Hide Description The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment. The PFS rate at Month 12 is presented.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
59.6
(54.3 to 64.5)
46.1
(40.5 to 51.5)
9.Secondary Outcome
Title Progression Free Survival Rate (PFS Rate) at Month 18 in All Participants
Hide Description The PFS rate was determined in all participants at Month 18. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment. The PFS rate at Month 18 is presented.
Time Frame Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
41.1
(33.5 to 48.5)
32.8
(25.4 to 40.4)
10.Secondary Outcome
Title Progression Free Survival Rate (PFS Rate) at Month 24 in All Participants
Hide Description The PFS rate was determined in all participants at Month 24. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The date of PD was approximated by the date of the first assessment at which PD was documented per RECIST 1.1 by Blinded Independent Central Review (BICR). Death was always considered as confirmed PD. Participants who did not experience PFS were censored at the last disease assessment.
Time Frame Month 24
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Overall Survival (OS) Rate at Month 12 in All Participants
Hide Description The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 is presented.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
89.9
(86.4 to 92.4)
78.3
(73.8 to 82.1)
12.Secondary Outcome
Title Overall Survival (OS) Rate at Month 18 in All Participants
Hide Description The OS rate was determined for all participants at Month 18 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 18 is presented.
Time Frame Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 432 429
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
82.3
(77.2 to 86.3)
72.1
(66.3 to 77.0)
13.Secondary Outcome
Title Overall Survival (OS) Rate at Month 24 in All Participants
Hide Description The OS rate was determined for all participants at Month 24 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment.
Time Frame Month 24
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Time to True Deterioration (TTD) of the Functional Assessment of Cancer Therapy Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) Score
Hide Description TTD was defined as time (in months) from the first dose of study treatment to the date of deterioration of FKSI-DRS Score. The FKSI-DRS was a questionnaire that asked the participant to rate 9 kidney cancer-related symptoms: lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or blood in the urine. Each item was scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. Deterioration was defined as a 3-point decrease (i.e. lower score) in symptom score and the time to true deterioration was the time to first onset of 3 or more decreases from baseline with confirmation under right-censoring rule (the last observation). The time to true deterioration as measured in months is presented.
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study medication and completed at least 1 questionnaire assessment.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 395 387
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(12.7 to NA)
NA [2] 
(NA to NA)
[1]
TTD median not reached by the time of the data cutoff (24-Aug-2018). For TTD upper limit, no deterioration reached by the time of last disease assessment.
[2]
TTD median not reached by the time of the data cutoff (24-Aug-2018). For TTD lower and upper limit, no deterioration reached by the time of last disease assessment.
15.Secondary Outcome
Title Least Squares (LS) Mean Change From Baseline to Week 54 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score
Hide Description EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 54
Outcome Measure Data Not Reported
16.Other Pre-specified Outcome
Title Mean Baseline EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Score
Hide Description EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The mean baseline EORTC QLQ-C30 score is presented.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days])
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with non-missing questionnaire assessments at baseline.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 394 410
Mean (Standard Deviation)
Unit of Measure: Score on a scale
70.90  (21.037) 72.07  (20.642)
17.Post-Hoc Outcome
Title Least Squares (LS) Mean Change From Baseline to Week 30 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score
Hide Description EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life on a 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100; with a high score indicating improved health status. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The LS Mean change from baseline to Week 30 is presented.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study medication and had non-missing questionnaire assessments at baseline and Week 30.
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
Overall Number of Participants Analyzed 427 423
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-4.05
(-6.03 to -2.07)
-2.35
(-4.44 to -0.26)
Time Frame Through Database Cutoff Date of 24-Aug-2018 (up to approximately 22 months)
Adverse Event Reporting Description Population: All participants who received ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs.
 
Arm/Group Title Pembrolizumab + Axitinib Sunitinib
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily. Participants received sunitinib 50 mg orally once daily for 4 weeks and then were off treatment for 2 weeks.
All-Cause Mortality
Pembrolizumab + Axitinib Sunitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   59/432 (13.66%)      97/429 (22.61%)    
Hide Serious Adverse Events
Pembrolizumab + Axitinib Sunitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   173/429 (40.33%)      133/425 (31.29%)    
Blood and lymphatic system disorders     
Anaemia † 1  2/429 (0.47%)  2 3/425 (0.71%)  3
Anaemia of malignant disease † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cytopenia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Disseminated intravascular coagulation † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Thrombocytopenia † 1  0/429 (0.00%)  0 4/425 (0.94%)  4
Thrombocytopenic purpura † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cardiac disorders     
Acute myocardial infarction † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Angina unstable † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Atrial fibrillation † 1  4/429 (0.93%)  4 0/425 (0.00%)  0
Atrial flutter † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Cardiac amyloidosis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cardiac arrest † 1  1/429 (0.23%)  1 2/425 (0.47%)  2
Cardiac failure † 1  1/429 (0.23%)  1 2/425 (0.47%)  3
Cardiac failure acute † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Cardiac failure chronic † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cardiac failure congestive † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Cardiac tamponade † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cardiac ventricular thrombosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Coronary artery occlusion † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Coronary artery stenosis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Myocardial infarction † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Myocarditis † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Sinus tachycardia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Endocrine disorders     
Adrenal insufficiency † 1  4/429 (0.93%)  4 0/425 (0.00%)  0
Adrenocorticotropic hormone deficiency † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Hyperthyroidism † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Hypophysitis † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Hypothyroidism † 1  1/429 (0.23%)  1 2/425 (0.47%)  2
Secondary adrenocortical insufficiency † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Eye disorders     
Vitreous floaters † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gastrointestinal disorders     
Abdominal adhesions † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Abdominal pain † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Abdominal wall haematoma † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Anal inflammation † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Ascites † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Colitis † 1  3/429 (0.70%)  3 0/425 (0.00%)  0
Diarrhoea † 1  12/429 (2.80%)  12 4/425 (0.94%)  4
Duodenal perforation † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Enteritis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Enterocolitis † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Enterocolitis haemorrhagic † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gastric haemorrhage † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Gastroduodenitis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gastrointestinal angiodysplasia † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Gastrointestinal haemorrhage † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Gastrointestinal perforation † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gastrointestinal toxicity † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Gastrooesophageal reflux disease † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Haematochezia † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Haemorrhoids † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Ileus † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Mallory-Weiss syndrome † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Melaena † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Mouth haemorrhage † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Nausea † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Oesophagitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Pancreatitis † 1  2/429 (0.47%)  2 2/425 (0.47%)  2
Pneumatosis intestinalis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Small intestinal obstruction † 1  1/429 (0.23%)  2 0/425 (0.00%)  0
Stomatitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Upper gastrointestinal haemorrhage † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Vomiting † 1  2/429 (0.47%)  2 2/425 (0.47%)  2
General disorders     
Asthenia † 1  3/429 (0.70%)  3 4/425 (0.94%)  4
Chest pain † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Condition aggravated † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Death † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Fatigue † 1  0/429 (0.00%)  0 3/425 (0.71%)  3
Gait disturbance † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
General physical health deterioration † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Malaise † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Mucosal inflammation † 1  1/429 (0.23%)  1 2/425 (0.47%)  2
Non-cardiac chest pain † 1  1/429 (0.23%)  1 1/425 (0.24%)  3
Pyrexia † 1  3/429 (0.70%)  3 1/425 (0.24%)  1
Strangulated hernia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Sudden cardiac death † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Sudden death † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Hepatobiliary disorders     
Autoimmune hepatitis † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Cholangitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cholecystitis † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Cholecystitis acute † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Cholelithiasis † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Drug-induced liver injury † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Hepatic cirrhosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Hepatic function abnormal † 1  5/429 (1.17%)  5 0/425 (0.00%)  0
Hepatic pain † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Hepatitis † 1  3/429 (0.70%)  3 0/425 (0.00%)  0
Hepatitis fulminant † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Hepatocellular injury † 1  3/429 (0.70%)  3 1/425 (0.24%)  1
Hepatotoxicity † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Immune-mediated hepatitis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Jaundice cholestatic † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Immune system disorders     
Anaphylactic reaction † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Contrast media allergy † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Contrast media reaction † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Hypersensitivity † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Infections and infestations     
Acute hepatitis C † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Anal abscess † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Appendicitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Bacterial sepsis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Bronchitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cellulitis † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Clostridium difficile infection † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Colonic abscess † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Device related infection † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Extrapulmonary tuberculosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gastroenteritis † 1  3/429 (0.70%)  3 1/425 (0.24%)  1
Herpes zoster † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Infection † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Influenza † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Klebsiella infection † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Labyrinthitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Lower respiratory tract infection † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Lung infection † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Necrotising fasciitis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Oral fungal infection † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Osteomyelitis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Pancreas infection † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Perineal abscess † 1  0/429 (0.00%)  0 1/425 (0.24%)  2
Periodontitis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Peritonitis † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Peritonsillar abscess † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Pneumonia † 1  4/429 (0.93%)  4 10/425 (2.35%)  12
Sepsis † 1  1/429 (0.23%)  1 2/425 (0.47%)  3
Skin infection † 1  0/429 (0.00%)  0 1/425 (0.24%)  2
Upper respiratory tract infection † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Urinary tract infection † 1  3/429 (0.70%)  4 3/425 (0.71%)  3
Injury, poisoning and procedural complications     
Carbon monoxide poisoning † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Comminuted fracture † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Femur fracture † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Fibula fracture † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Head injury † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Humerus fracture † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Incisional hernia † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Multiple fractures † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Pelvic fracture † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Postoperative respiratory failure † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Radiation necrosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Rib fracture † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Tendon rupture † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Thoracic vertebral fracture † 1  1/429 (0.23%)  2 0/425 (0.00%)  0
Tibia fracture † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Traumatic haemothorax † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Wound dehiscence † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Investigations     
Alanine aminotransferase increased † 1  6/429 (1.40%)  6 0/425 (0.00%)  0
Aspartate aminotransferase increased † 1  5/429 (1.17%)  5 0/425 (0.00%)  0
Blood bilirubin increased † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Blood creatine phosphokinase increased † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Blood electrolytes abnormal † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Blood pressure decreased † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Hepatic enzyme increased † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Liver function test increased † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Platelet count decreased † 1  0/429 (0.00%)  0 3/425 (0.71%)  3
Transaminases increased † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Dehydration † 1  6/429 (1.40%)  7 5/425 (1.18%)  5
Diabetes mellitus † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Diabetic ketoacidosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Electrolyte imbalance † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Failure to thrive † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Gout † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Hypercalcaemia † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Hyperglycaemia † 1  3/429 (0.70%)  3 0/425 (0.00%)  0
Hyperkalaemia † 1  1/429 (0.23%)  2 1/425 (0.24%)  1
Hypoglycaemia † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Hypokalaemia † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Hyponatraemia † 1  2/429 (0.47%)  2 5/425 (1.18%)  5
Hypophosphataemia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Ketoacidosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Metabolic acidosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Arthritis † 1  1/429 (0.23%)  2 0/425 (0.00%)  0
Back pain † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Bone pain † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Muscular weakness † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Musculoskeletal chest pain † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Musculoskeletal pain † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Myalgia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Myositis † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Neck pain † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Pathological fracture † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Polymyalgia rheumatica † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain † 1  1/429 (0.23%)  1 2/425 (0.47%)  2
Colon cancer † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Endometrial cancer † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Invasive ductal breast carcinoma † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Malignant neoplasm progression † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Paraneoplastic syndrome † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Plasma cell myeloma † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Squamous cell carcinoma † 1  0/429 (0.00%)  0 1/425 (0.24%)  3
Tumour pain † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Nervous system disorders     
Aphasia † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cerebellar infarction † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Cerebral infarction † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Cerebrovascular accident † 1  4/429 (0.93%)  4 1/425 (0.24%)  1
Epilepsy † 1  0/429 (0.00%)  0 1/425 (0.24%)  2
Facial paresis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Haemorrhage intracranial † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Headache † 1  3/429 (0.70%)  4 1/425 (0.24%)  1
Myasthenia gravis † 1  4/429 (0.93%)  4 0/425 (0.00%)  0
Pachymeningitis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Presyncope † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Spinal cord compression † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Transient ischaemic attack † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Psychiatric disorders     
Dependence † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Suicide attempt † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Renal and urinary disorders     
Acute kidney injury † 1  7/429 (1.63%)  8 3/425 (0.71%)  3
Calculus urinary † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Chronic kidney disease † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Haematuria † 1  1/429 (0.23%)  1 2/425 (0.47%)  2
Nephritis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Nephropathy toxic † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Proteinuria † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Renal colic † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Renal failure † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Renal haemorrhage † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Renal impairment † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Tubulointerstitial nephritis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Ureterolithiasis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease † 1  2/429 (0.47%)  2 0/425 (0.00%)  0
Dyspnoea † 1  3/429 (0.70%)  3 2/425 (0.47%)  2
Dyspnoea exertional † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Epiglottic cyst † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Haemoptysis † 1  0/429 (0.00%)  0 2/425 (0.47%)  2
Hypoxia † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Interstitial lung disease † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Pleural effusion † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Pneumonia aspiration † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Pneumonitis † 1  5/429 (1.17%)  5 0/425 (0.00%)  0
Pulmonary artery thrombosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Pulmonary embolism † 1  4/429 (0.93%)  4 7/425 (1.65%)  7
Pulmonary haemorrhage † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Pulmonary thrombosis † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Respiratory failure † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Skin and subcutaneous tissue disorders     
Drug eruption † 1  1/429 (0.23%)  1 1/425 (0.24%)  1
Palmar-plantar erythrodysaesthesia syndrome † 1  2/429 (0.47%)  2 1/425 (0.24%)  1
Rash maculo-papular † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Skin ulcer † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Angioedema † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Vascular disorders     
Hypertension † 1  2/429 (0.47%)  2 2/425 (0.47%)  2
Hypertensive crisis † 1  0/429 (0.00%)  0 1/425 (0.24%)  1
Peripheral artery occlusion † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
Venous thrombosis limb † 1  1/429 (0.23%)  1 0/425 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab + Axitinib Sunitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   417/429 (97.20%)      415/425 (97.65%)    
Blood and lymphatic system disorders     
Anaemia † 1  32/429 (7.46%)  34 97/425 (22.82%)  152
Leukopenia † 1  6/429 (1.40%)  11 41/425 (9.65%)  79
Neutropenia † 1  8/429 (1.86%)  11 82/425 (19.29%)  152
Thrombocytopenia † 1  11/429 (2.56%)  13 95/425 (22.35%)  164
Endocrine disorders     
Hyperthyroidism † 1  53/429 (12.35%)  58 16/425 (3.76%)  18
Hypothyroidism † 1  152/429 (35.43%)  177 133/425 (31.29%)  172
Gastrointestinal disorders     
Abdominal pain † 1  48/429 (11.19%)  64 29/425 (6.82%)  32
Abdominal pain upper † 1  26/429 (6.06%)  35 26/425 (6.12%)  31
Constipation † 1  89/429 (20.75%)  107 62/425 (14.59%)  70
Diarrhoea † 1  231/429 (53.85%)  496 191/425 (44.94%)  380
Dry mouth † 1  25/429 (5.83%)  27 25/425 (5.88%)  26
Dyspepsia † 1  22/429 (5.13%)  26 62/425 (14.59%)  73
Gastrooesophageal reflux disease † 1  18/429 (4.20%)  18 48/425 (11.29%)  60
Nausea † 1  119/429 (27.74%)  174 134/425 (31.53%)  205
Stomatitis † 1  67/429 (15.62%)  86 88/425 (20.71%)  110
Vomiting † 1  64/429 (14.92%)  97 78/425 (18.35%)  125
General disorders     
Asthenia † 1  62/429 (14.45%)  85 60/425 (14.12%)  77
Fatigue † 1  165/429 (38.46%)  208 158/425 (37.18%)  211
Mucosal inflammation † 1  56/429 (13.05%)  77 92/425 (21.65%)  143
Oedema peripheral † 1  28/429 (6.53%)  29 34/425 (8.00%)  43
Pyrexia † 1  53/429 (12.35%)  65 42/425 (9.88%)  46
Infections and infestations     
Nasopharyngitis † 1  33/429 (7.69%)  41 15/425 (3.53%)  23
Upper respiratory tract infection † 1  27/429 (6.29%)  31 20/425 (4.71%)  20
Urinary tract infection † 1  37/429 (8.62%)  54 25/425 (5.88%)  28
Investigations     
Alanine aminotransferase increased † 1  110/429 (25.64%)  158 64/425 (15.06%)  81
Aspartate aminotransferase increased † 1  108/429 (25.17%)  163 69/425 (16.24%)  95
Blood alkaline phosphatase increased † 1  27/429 (6.29%)  32 19/425 (4.47%)  21
Blood bilirubin increased † 1  28/429 (6.53%)  45 24/425 (5.65%)  39
Blood creatinine increased † 1  48/429 (11.19%)  79 51/425 (12.00%)  72
Blood thyroid stimulating hormone increased † 1  23/429 (5.36%)  25 22/425 (5.18%)  28
Neutrophil count decreased † 1  4/429 (0.93%)  6 50/425 (11.76%)  109
Platelet count decreased † 1  16/429 (3.73%)  21 76/425 (17.88%)  148
Weight decreased † 1  76/429 (17.72%)  86 47/425 (11.06%)  54
White blood cell count decreased † 1  2/429 (0.47%)  2 43/425 (10.12%)  97
Metabolism and nutrition disorders     
Decreased appetite † 1  126/429 (29.37%)  173 125/425 (29.41%)  156
Hyperglycaemia † 1  31/429 (7.23%)  53 20/425 (4.71%)  26
Hyperkalaemia † 1  30/429 (6.99%)  62 14/425 (3.29%)  16
Hypophosphataemia † 1  9/429 (2.10%)  20 36/425 (8.47%)  57
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  78/429 (18.18%)  95 25/425 (5.88%)  33
Back pain † 1  55/429 (12.82%)  64 42/425 (9.88%)  45
Musculoskeletal pain † 1  26/429 (6.06%)  29 18/425 (4.24%)  19
Myalgia † 1  36/429 (8.39%)  41 19/425 (4.47%)  23
Pain in extremity † 1  51/429 (11.89%)  69 42/425 (9.88%)  48
Nervous system disorders     
Dizziness † 1  22/429 (5.13%)  25 28/425 (6.59%)  31
Dysgeusia † 1  47/429 (10.96%)  52 131/425 (30.82%)  185
Headache † 1  67/429 (15.62%)  91 68/425 (16.00%)  87
Psychiatric disorders     
Insomnia † 1  36/429 (8.39%)  40 39/425 (9.18%)  39
Renal and urinary disorders     
Haematuria † 1  22/429 (5.13%)  23 20/425 (4.71%)  27
Proteinuria † 1  74/429 (17.25%)  104 47/425 (11.06%)  77
Respiratory, thoracic and mediastinal disorders     
Cough † 1  91/429 (21.21%)  108 58/425 (13.65%)  66
Dysphonia † 1  109/429 (25.41%)  126 14/425 (3.29%)  18
Dyspnoea † 1  69/429 (16.08%)  80 44/425 (10.35%)  49
Epistaxis † 1  27/429 (6.29%)  30 40/425 (9.41%)  45
Oropharyngeal pain † 1  28/429 (6.53%)  31 19/425 (4.47%)  27
Skin and subcutaneous tissue disorders     
Dry skin † 1  29/429 (6.76%)  31 39/425 (9.18%)  47
Palmar-plantar erythrodysaesthesia syndrome † 1  118/429 (27.51%)  140 169/425 (39.76%)  235
Pruritus † 1  65/429 (15.15%)  78 25/425 (5.88%)  33
Rash † 1  61/429 (14.22%)  84 47/425 (11.06%)  60
Vascular disorders     
Hypertension † 1  189/429 (44.06%)  317 192/425 (45.18%)  278
1
Term from vocabulary, MedDRA 21.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
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: NCT02853331    
Other Study ID Numbers: 3475-426
163460 ( Registry Identifier: JAPIC-CTI )
MK-3475-426 ( Other Identifier: Merck )
KEYNOTE-426 ( Other Identifier: Merck )
2016-000588-17 ( EudraCT Number )
First Submitted: July 29, 2016
First Posted: August 2, 2016
Results First Submitted: October 18, 2019
Results First Posted: November 8, 2019
Last Update Posted: March 7, 2024