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A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)

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ClinicalTrials.gov Identifier: NCT02256436
Recruitment Status : Active, not recruiting
First Posted : October 3, 2014
Results First Posted : August 31, 2017
Last Update Posted : December 20, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Urothelial Cancer
Interventions Biological: pembrolizumab
Drug: paclitaxel
Drug: vinflunine
Drug: docetaxel
Enrollment 542

Recruitment Details  
Pre-assignment Details This interim analysis of the results disclosure is based on data collected prior to the database cutoff date of 07-Sep-2016 (up to approximately 20 months of follow up from study start), at which time, 175 participants were ongoing in the study.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W). Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Period Title: Overall Study
Started 270 272
Treated 266 255
Completed 0 0
Not Completed 270 272
Reason Not Completed
Adverse Event             15             13
Death             137             158
Lost to Follow-up             1             1
Physician Decision             1             3
Protocol Violation             1             0
Withdrawal by Subject             7             30
Ongoing in Study             108             67
Arm/Group Title Pembrolizumab Active Comparator Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg IV on Day 1 Q3W. Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W. Total of all reporting groups
Overall Number of Baseline Participants 270 272 542
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 270 participants 272 participants 542 participants
66.0  (10.2) 65.1  (9.2) 65.5  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 270 participants 272 participants 542 participants
Female
70
  25.9%
70
  25.7%
140
  25.8%
Male
200
  74.1%
202
  74.3%
402
  74.2%
1.Primary Outcome
Title Overall Survival (OS) - All Participants
Hide Description OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 270 272
Median (95% Confidence Interval)
Unit of Measure: Months
10.3
(8.0 to 11.8)
7.4
(6.1 to 8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments OS - All Participants (Note: ECOG PS=Eastern Cooperative Oncology Group Performance Status)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00224
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.59 to 0.91
Estimation Comments [Not Specified]
2.Primary Outcome
Title Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants
Hide Description PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent radiologist review in all participants up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 270 272
Median (95% Confidence Interval)
Unit of Measure: Months
2.1
(2.0 to 2.2)
3.3
(2.3 to 3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments PFS - All Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41648
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.81 to 1.19
Estimation Comments [Not Specified]
3.Primary Outcome
Title OS - Participants With Strongly PD-L1 Positive Tumors
Hide Description OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a programmed cell death-ligand 1 (PD-L1) combined proportion score (CPS) ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 74 90
Median (95% Confidence Interval)
Unit of Measure: Months
8.0
(5.0 to 12.3)
5.2
(4.0 to 7.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments OS - Strongly PD-L1 positive participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00483
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.37 to 0.88
Estimation Comments [Not Specified]
4.Primary Outcome
Title PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
Hide Description PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by blinded independent radiologist review in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 74 90
Median (95% Confidence Interval)
Unit of Measure: Months
2.1
(1.9 to 2.1)
3.1
(2.2 to 3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments PFS - Strongly PD-L1 positive participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23958
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.61 to 1.28
Estimation Comments [Not Specified]
5.Primary Outcome
Title OS - Participants With PD-L1 Positive Tumors
Hide Description OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 110 120
Median (95% Confidence Interval)
Unit of Measure: Months
11.3
(7.7 to 16.0)
6.9
(4.7 to 8.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments OS - PD-L1 positive participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00239
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.43 to 0.86
Estimation Comments [Not Specified]
6.Primary Outcome
Title PFS Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
Hide Description PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by blinded independent radiologist review in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 110 120
Median (95% Confidence Interval)
Unit of Measure: Months
2.1
(2.0 to 2.4)
3.2
(2.2 to 3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments PFS - PD-L1 positive participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26443
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.68 to 1.24
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST 1.1 - All Participants
Hide Description ORR 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: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by blinded independent radiologist review in all participants up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 270 272
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
21.1
(16.4 to 26.5)
11.4
(7.9 to 15.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments ORR per RECIST 1.1 - All Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00106
Comments One-sided p-value for testing H0: difference in %=0; H1: difference in %>0
Method Miettinen & Nurminene method
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 9.6
Confidence Interval (2-Sided) 95%
3.5 to 15.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title ORR Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
Hide Description ORR 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: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by blinded independent radiologist review in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 74 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
21.6
(12.9 to 32.7)
6.7
(2.5 to 13.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments ORR per RECIST 1.1 - Strongly PD-L1 Positive Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00020
Comments One-sided p-value for testing H0: difference in %=0; H1: difference in %>0
Method Miettinen & Nurminen method
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 19.3
Confidence Interval (2-Sided) 95%
8.6 to 31.7
Estimation Comments [Not Specified]
9.Secondary Outcome
Title ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
Hide Description ORR 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: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by blinded independent radiologist review in participants with PD-L1 positive tumors (CPS ≥1%) up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 110 120
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
23.6
(16.1 to 32.7)
8.3
(4.1 to 14.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments ORR per RECIST 1.1 - PD-L1 Positive Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00022
Comments One-sided p-value for testing H0: difference in %=0; H1: difference in %>0
Method Miettinen & Nurminen method
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 16.9
Confidence Interval (2-Sided) 95%
7.7 to 27.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title PFS Per Modified RECIST - All Participants
Hide Description PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per modified (immune-related [ir]) RECIST, progressive disease (irPD) was defined as: increase in tumor burden ≥25% relative to minimum recorded tumor burden confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented. PFS per modified RECIST was assessed by blinded independent radiologist review in all randomized participants up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 270 272
Median (95% Confidence Interval)
Unit of Measure: Months
2.2
(2.1 to 3.4)
3.5
(3.1 to 4.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments PFS per Modified RECIST - All Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16411
Comments One-sided p-value based on stratified log-rank test
Method Regression, Cox
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.74 to 1.11
Estimation Comments [Not Specified]
11.Secondary Outcome
Title ORR Per Modified RECIST - All Participants
Hide Description ORR per modified RECIST was defined as the percentage of participants in the analysis population who had a Complete Response (irCR: complete disappearance of all lesions [and no new lesions] confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a Partial Response (irPR: decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per modified RECIST was assessed by blinded independent radiologist review in all participants up through the database cutoff date of 07-Sep-2016.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 270 272
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
25.2
(20.1 to 30.8)
11.8
(8.2 to 16.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments All Participants
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00002
Comments One-sided p-value for testing H0: difference in %=0; H1: difference in %>0
Method Miettinen & Nurminen method
Comments Treatment as a covariate stratified by ECOG PS, presence/absence of liver metastases, hemoglobin and time from completion of most recent chemotherapy
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
7.0 to 19.9
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE was 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 were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was assessed.
Time Frame Up to approximately 23 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 266 255
Measure Type: Number
Unit of Measure: Participants
248 250
13.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description An AE was 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 discontinued study treatment due to an AE was assessed.
Time Frame Up to approximately 20 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 266 255
Measure Type: Number
Unit of Measure: Participants
22 32
14.Secondary Outcome
Title Response Duration Per RECIST 1.1 - All Participants
Hide Description For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, response duration was defined as the time from first documented evidence of CR or PR until disease progression or death. Response duration for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Response duration was assessed in all participants based on independent radiologist review and was analyzed using the Kaplan-Meier method.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 57 31
Median (Full Range)
Unit of Measure: Months
NA [1] 
(1.6 to NA)
4.3
(1.4 to 15.4)
[1]
NA=Not reached
15.Secondary Outcome
Title Response Duration Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
Hide Description For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, response duration was defined as the time from first documented evidence of CR or PR until disease progression or death. Response duration for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Response duration was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on independent radiologist review and was analyzed using the Kaplan-Meier method.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized strongly PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 16 6
Median (Full Range)
Unit of Measure: Months
NA [1] 
(1.6 to NA)
4.4
(1.5 to 10.8)
[1]
NA=Not reached
16.Secondary Outcome
Title Response Duration Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
Hide Description For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, response duration was defined as the time from first documented evidence of CR or PR until disease progression or death. Response duration for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Response duration was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on independent radiologist review and was analyzed using the Kaplan-Meier method.
Time Frame Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized PD-L1 positive participants, regardless of whether or not they received study treatment. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W.
Overall Number of Participants Analyzed 26 10
Median (Full Range)
Unit of Measure: Months
NA [1] 
(1.6 to NA)
NA [1] 
(1.5 to NA)
[1]
NA=Not reached
Time Frame Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 21 months) Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 23 months)
Adverse Event Reporting Description The safety population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
 
Arm/Group Title Active Comparator Pembrolizumab
Hide Arm/Group Description Participants received paclitaxel 175 mg/m^2 IV or docetaxel 75 mg/m^2 IV or vinflunine 320 mg/m^2 IV on Day 1 Q3W. Participants received pembrolizumab 200 mg IV on Day 1 Q3W.
All-Cause Mortality
Active Comparator Pembrolizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Active Comparator Pembrolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   104/255 (40.78%)      104/266 (39.10%)    
Blood and lymphatic system disorders     
Anaemia  1  8/255 (3.14%)  9 7/266 (2.63%)  8
Anaemia of malignant disease  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Febrile neutropenia  1  15/255 (5.88%)  15 0/266 (0.00%)  0
Leukopenia  1  2/255 (0.78%)  5 0/266 (0.00%)  0
Nephrogenic anaemia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Neutropenia  1  5/255 (1.96%)  5 0/266 (0.00%)  0
Normochromic normocytic anaemia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Pancytopenia  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Thrombocytopenia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Atrial fibrillation  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Atrial flutter  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Atrioventricular block  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Myocardial infarction  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pericardial effusion  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Sinus tachycardia  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Endocrine disorders     
Adrenal insufficiency  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Hypercalcaemia of malignancy  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Hyperthyroidism  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  4/255 (1.57%)  4 2/266 (0.75%)  2
Anal incontinence  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Colitis  1  0/255 (0.00%)  0 4/266 (1.50%)  4
Colonic pseudo-obstruction  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Constipation  1  7/255 (2.75%)  7 0/266 (0.00%)  0
Diarrhoea  1  2/255 (0.78%)  2 3/266 (1.13%)  4
Enterocolitis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Enterocutaneous fistula  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Gastrointestinal haemorrhage  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Gastrointestinal perforation  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Ileus  1  3/255 (1.18%)  4 0/266 (0.00%)  0
Ileus paralytic  1  2/255 (0.78%)  3 0/266 (0.00%)  0
Intestinal obstruction  1  8/255 (3.14%)  8 0/266 (0.00%)  0
Large intestinal obstruction  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Nausea  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Neutropenic colitis  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Small intestinal obstruction  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Subileus  1  2/255 (0.78%)  3 0/266 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Vomiting  1  1/255 (0.39%)  2 1/266 (0.38%)  1
General disorders     
Asthenia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Death  1  4/255 (1.57%)  4 1/266 (0.38%)  1
Fatigue  1  1/255 (0.39%)  1 2/266 (0.75%)  2
General physical health deterioration  1  0/255 (0.00%)  0 3/266 (1.13%)  3
Hyperthermia malignant  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Influenza like illness  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Malaise  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Mucosal inflammation  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Pyrexia  1  5/255 (1.96%)  5 5/266 (1.88%)  5
Hepatobiliary disorders     
Hepatic pain  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Hyperbilirubinaemia  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Jaundice  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Anal abscess  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Atypical pneumonia  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Bacteraemia  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Catheter site infection  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Cystitis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Device related infection  1  0/255 (0.00%)  0 1/266 (0.38%)  2
Device related sepsis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Gastroenteritis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Gastroenteritis viral  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Infective exacerbation of chronic obstructive airways disease  1  1/255 (0.39%)  1 1/266 (0.38%)  2
Influenza  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Lower respiratory tract infection  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Lung infection  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Nasopharyngitis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Necrotising fasciitis  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Osteomyelitis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pelvic infection  1  0/255 (0.00%)  0 1/266 (0.38%)  2
Pneumocystis jirovecii infection  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Pneumonia  1  8/255 (3.14%)  9 9/266 (3.38%)  9
Post procedural infection  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Psoas abscess  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pyelonephritis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Respiratory tract infection  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Respiratory tract infection viral  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Sepsis  1  5/255 (1.96%)  6 0/266 (0.00%)  0
Septic shock  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Tooth abscess  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Upper respiratory tract infection  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Urinary tract infection  1  12/255 (4.71%)  13 12/266 (4.51%)  15
Urosepsis  1  1/255 (0.39%)  1 4/266 (1.50%)  5
Injury, poisoning and procedural complications     
Craniocerebral injury  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Fall  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Hip fracture  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Incisional hernia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Pelvic fracture  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Post procedural haemorrhage  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Procedural pain  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Stoma site haemorrhage  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Thoracic vertebral fracture  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Toxicity to various agents  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Wrist fracture  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Investigations     
Alanine aminotransferase increased  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Aspartate aminotransferase increased  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Bacterial test positive  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Blood calcium increased  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Blood creatinine increased  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Neutrophil count decreased  1  3/255 (1.18%)  3 0/266 (0.00%)  0
Platelet count decreased  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Transaminases increased  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Metabolism and nutrition disorders     
Cachexia  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Decreased appetite  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Dehydration  1  2/255 (0.78%)  3 3/266 (1.13%)  3
Electrolyte imbalance  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Fluid retention  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Hypercalcaemia  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Hyponatraemia  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Type 2 diabetes mellitus  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Vitamin B1 deficiency  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Bone pain  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Gouty arthritis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pain in extremity  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Pathological fracture  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Periostitis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Tendonitis  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  3/255 (1.18%)  3 4/266 (1.50%)  5
Lung neoplasm malignant  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Malignant neoplasm progression  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Malignant pleural effusion  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Metastases to central nervous system  1  0/255 (0.00%)  0 1/266 (0.38%)  2
Tumour haemorrhage  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Tumour pain  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Urethral cancer  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Nervous system disorders     
Cerebral infarction  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Encephalopathy  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Posterior reversible encephalopathy syndrome  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Somnolence  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Syncope  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Transient ischaemic attack  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Product Issues     
Device dislocation  1  0/255 (0.00%)  0 3/266 (1.13%)  3
Device malfunction  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Renal and urinary disorders     
Acute kidney injury  1  6/255 (2.35%)  6 4/266 (1.50%)  4
Autoimmune nephritis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Azotaemia  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Bladder neck obstruction  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Haematuria  1  5/255 (1.96%)  6 5/266 (1.88%)  5
Hydronephrosis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Nephritis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Prerenal failure  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Renal failure  1  1/255 (0.39%)  1 2/266 (0.75%)  2
Renal injury  1  0/255 (0.00%)  0 1/266 (0.38%)  2
Urinary fistula  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Urinary retention  1  2/255 (0.78%)  2 0/266 (0.00%)  0
Urinary tract obstruction  1  1/255 (0.39%)  1 3/266 (1.13%)  3
Reproductive system and breast disorders     
Female genital tract fistula  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pelvic fluid collection  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Pelvic pain  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Prostatic obstruction  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/255 (0.00%)  0 2/266 (0.75%)  2
Dyspnoea  1  2/255 (0.78%)  2 3/266 (1.13%)  3
Haemoptysis  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Interstitial lung disease  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pleurisy  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Pneumonitis  1  0/255 (0.00%)  0 6/266 (2.26%)  7
Pulmonary embolism  1  1/255 (0.39%)  1 1/266 (0.38%)  1
Pulmonary hypertension  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Vascular disorders     
Deep vein thrombosis  1  2/255 (0.78%)  2 2/266 (0.75%)  2
Embolism  1  1/255 (0.39%)  1 0/266 (0.00%)  0
Hypertension  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Hypovolaemic shock  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Thrombosis  1  0/255 (0.00%)  0 1/266 (0.38%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Comparator Pembrolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   233/255 (91.37%)      223/266 (83.83%)    
Blood and lymphatic system disorders     
Anaemia  1  84/255 (32.94%)  132 43/266 (16.17%)  59
Neutropenia  1  39/255 (15.29%)  70 0/266 (0.00%)  0
Endocrine disorders     
Hypothyroidism  1  3/255 (1.18%)  3 17/266 (6.39%)  18
Gastrointestinal disorders     
Abdominal pain  1  31/255 (12.16%)  38 32/266 (12.03%)  36
Abdominal pain upper  1  14/255 (5.49%)  16 9/266 (3.38%)  11
Constipation  1  79/255 (30.98%)  105 50/266 (18.80%)  59
Diarrhoea  1  46/255 (18.04%)  68 42/266 (15.79%)  66
Nausea  1  73/255 (28.63%)  100 55/266 (20.68%)  60
Stomatitis  1  22/255 (8.63%)  34 6/266 (2.26%)  7
Vomiting  1  34/255 (13.33%)  47 38/266 (14.29%)  47
General disorders     
Asthenia  1  52/255 (20.39%)  67 30/266 (11.28%)  32
Fatigue  1  85/255 (33.33%)  107 67/266 (25.19%)  83
Mucosal inflammation  1  18/255 (7.06%)  24 5/266 (1.88%)  7
Oedema peripheral  1  40/255 (15.69%)  48 26/266 (9.77%)  28
Pyrexia  1  29/255 (11.37%)  37 34/266 (12.78%)  42
Infections and infestations     
Urinary tract infection  1  25/255 (9.80%)  28 30/266 (11.28%)  39
Investigations     
Blood creatinine increased  1  13/255 (5.10%)  16 13/266 (4.89%)  19
Neutrophil count decreased  1  36/255 (14.12%)  69 1/266 (0.38%)  1
Weight decreased  1  21/255 (8.24%)  22 24/266 (9.02%)  28
White blood cell count decreased  1  20/255 (7.84%)  38 1/266 (0.38%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  52/255 (20.39%)  64 56/266 (21.05%)  61
Hyponatraemia  1  18/255 (7.06%)  21 14/266 (5.26%)  16
Musculoskeletal and connective tissue disorders     
Arthralgia  1  30/255 (11.76%)  55 24/266 (9.02%)  26
Back pain  1  21/255 (8.24%)  22 37/266 (13.91%)  44
Myalgia  1  17/255 (6.67%)  24 14/266 (5.26%)  14
Pain in extremity  1  27/255 (10.59%)  31 21/266 (7.89%)  25
Nervous system disorders     
Dizziness  1  19/255 (7.45%)  26 15/266 (5.64%)  18
Dysgeusia  1  18/255 (7.06%)  21 7/266 (2.63%)  7
Headache  1  13/255 (5.10%)  17 13/266 (4.89%)  17
Neuropathy peripheral  1  31/255 (12.16%)  43 1/266 (0.38%)  1
Peripheral sensory neuropathy  1  28/255 (10.98%)  34 2/266 (0.75%)  3
Psychiatric disorders     
Insomnia  1  19/255 (7.45%)  19 16/266 (6.02%)  20
Renal and urinary disorders     
Haematuria  1  17/255 (6.67%)  20 27/266 (10.15%)  38
Respiratory, thoracic and mediastinal disorders     
Cough  1  18/255 (7.06%)  20 38/266 (14.29%)  47
Dyspnoea  1  22/255 (8.63%)  22 30/266 (11.28%)  35
Skin and subcutaneous tissue disorders     
Alopecia  1  99/255 (38.82%)  105 2/266 (0.75%)  2
Dry skin  1  9/255 (3.53%)  9 14/266 (5.26%)  16
Pruritus  1  14/255 (5.49%)  16 62/266 (23.31%)  78
Rash  1  16/255 (6.27%)  17 29/266 (10.90%)  34
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this 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.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02256436     History of Changes
Other Study ID Numbers: 3475-045
2014-002009-40 ( EudraCT Number )
152903 ( Registry Identifier: JAPIC-CTI )
MK-3475-045 ( Other Identifier: Merck Protocol Number )
First Submitted: September 29, 2014
First Posted: October 3, 2014
Results First Submitted: June 12, 2017
Results First Posted: August 31, 2017
Last Update Posted: December 20, 2017