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Trial record 1 of 1 for:    KEYNOTE-040
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Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02252042
Recruitment Status : Active, not recruiting
First Posted : September 29, 2014
Results First Posted : August 13, 2018
Last Update Posted : July 29, 2021
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 Head and Neck Squamous Cell Cancer
Interventions Biological: pembrolizumab
Drug: methotrexate
Drug: docetaxel
Biological: cetuximab
Enrollment 495
Recruitment Details  
Pre-assignment Details This results disclosure is based on a data cutoff date of 15 May 2017, at which time 99 participants were ongoing in the study.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle. Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Period Title: Overall Study
Started 247 248
Treated 246 [1] 234 [2]
Completed 0 0
Not Completed 247 248
Reason Not Completed
Death             170             192
Physician Decision             0             1
Withdrawal by Subject             13             20
Ongoing in study             64             35
[1]
1 participant was randomized but did not receive study treatment.
[2]
14 participants were randomized but did not receive study treatment.
Arm/Group Title Pembrolizumab Active Comparator Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle. Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle. Total of all reporting groups
Overall Number of Baseline Participants 247 248 495
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 247 participants 248 participants 495 participants
60.3  (9.8) 60.2  (8.6) 60.2  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
Female
40
  16.2%
43
  17.3%
83
  16.8%
Male
207
  83.8%
205
  82.7%
412
  83.2%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
American Indian or Alaska Native
2
   0.8%
0
   0.0%
2
   0.4%
Asian
15
   6.1%
16
   6.5%
31
   6.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   1.2%
7
   2.8%
10
   2.0%
White
207
  83.8%
207
  83.5%
414
  83.6%
More than one race
4
   1.6%
3
   1.2%
7
   1.4%
Unknown or Not Reported
16
   6.5%
15
   6.0%
31
   6.3%
[1]
Measure Description: The race of participants is presented.
Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
TPS=0%
103
  41.7%
93
  37.5%
196
  39.6%
1%<=TPS<50%
79
  32.0%
87
  35.1%
166
  33.5%
TPS >=50%
64
  25.9%
65
  26.2%
129
  26.1%
Missing
1
   0.4%
3
   1.2%
4
   0.8%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a TPS ≥50% were classified as PD-L1 strongly positive and participants with a TPS <50% were classified as not strongly positive.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
EGOG PS=0
71
  28.7%
67
  27.0%
138
  27.9%
ECOG PS=1
176
  71.3%
180
  72.6%
356
  71.9%
ECOG PS=2
0
   0.0%
1
   0.4%
1
   0.2%
[1]
Measure Description: Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature; Grade 2: Ambulatory & capable of all selfcare but unable to carry out any work activities, up & about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.
Human Papillomavirus (HPV) Tumor Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
Positive HPV Status
61
  24.7%
58
  23.4%
119
  24.0%
Negative HPV Status
186
  75.3%
190
  76.6%
376
  76.0%
[1]
Measure Description: Participants were assessed for the presence or absence of HPV in their tumors.
PD-L1 Combined Positive Score (CPS) Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
PD-L1 CPS <1
50
  20.2%
54
  21.8%
104
  21.0%
PD-L1 CPS ≥1
196
  79.4%
191
  77.0%
387
  78.2%
Missing
1
   0.4%
3
   1.2%
4
   0.8%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a CPS ≥1 were classified as PD-L1 positive and participants with a CPS <1 were classified as PD-L1 negative.
1.Primary Outcome
Title Initial Overall Survival (OS) for All Participants
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 final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
Time Frame Up to approximately 2 years (Database lock on 04-Jun-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
8.4
(6.5 to 9.4)
7.1
(5.9 to 8.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03160
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.67 to 1.01
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
2.Primary Outcome
Title Updated Final OS for All Participants
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 final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years (Database update on 13-Oct-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
8.4
(6.4 to 9.4)
6.9
(5.9 to 8.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01605
Comments Nominal p-value
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.65 to 0.98
Estimation Comments Nominal HR. Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
3.Secondary Outcome
Title OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
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 final analysis will be censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 196 191
Median (95% Confidence Interval)
Unit of Measure: Months
8.7
(6.9 to 11.4)
7.1
(5.7 to 8.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00493
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.58 to 0.93
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
4.Secondary Outcome
Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
Hide Description PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
2.1
(2.1 to 2.3)
2.3
(2.1 to 2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32504
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.79 to 1.16
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
5.Secondary Outcome
Title PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Hide Description PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 196 191
Median (95% Confidence Interval)
Unit of Measure: Months
2.2
(2.1 to 3.0)
2.3
(2.1 to 3.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07736
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.69 to 1.06
Estimation Comments Cox regression model with treatment as a single covariate
6.Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
Hide Description ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
14.6
(10.4 to 19.6)
10.1
(6.6 to 14.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0610
Comments [Not Specified]
Method Log Rank
Comments H0: difference in %=0; H1: difference in %>0
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-1.2 to 10.6
Estimation Comments Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
7.Secondary Outcome
Title ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Hide Description ORR was defined as the percentage of the 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 196 191
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
17.3
(12.3 to 23.4)
9.9
(6.1 to 15.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0171
Comments [Not Specified]
Method Log Rank
Comments H0: difference in %=0; H1: difference in %>0
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
0.6 to 14.6
Estimation Comments Stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
8.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 in All Participants
Hide Description For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 26 18
Median (Full Range)
Unit of Measure: Months
18.4
(2.7 to 18.4)
5.0
(1.4 to 18.8)
9.Secondary Outcome
Title DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Hide Description For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS who demonstrated a confirmed CR or PR per RECIST 1.1. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 26 15
Median (Full Range)
Unit of Measure: Months
18.4
(2.7 to 18.4)
9.6
(1.4 to 18.8)
10.Secondary Outcome
Title Time to Progression (TTP) Per RECIST 1.1 in All Participants
Hide Description TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
2.2
(2.1 to 3.3)
2.2
(2.1 to 3.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14545
Comments p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.70 to 1.12
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
11.Secondary Outcome
Title TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Hide Description TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
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Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 196 191
Median (Full Range)
Unit of Measure: Months
2.7
(2.1 to 3.5)
2.3
(2.1 to 3.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05851
Comments p-value stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.62 to 1.06
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
12.Secondary Outcome
Title PFS Per Modified RECIST in All Participants
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
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Hide Analysis Population Description
The efficacy population consisted of all randomized participants. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
3.5
(3.1 to 4.4)
4.8
(4.1 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65759
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.86 to 1.27
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
13.Secondary Outcome
Title PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population consisted of all randomized participants with PD-L1 ≥1% CPS. Participants are 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 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 196 191
Median (95% Confidence Interval)
Unit of Measure: Months
3.6
(3.1 to 4.6)
4.8
(4.1 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Active Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51982
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.81 to 1.26
Estimation Comments Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), HPV status (Positive vs. Negative) & PD-L1 status (Strongly Positive, Not Strongly Positive)
14.Secondary Outcome
Title Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
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 is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
Time Frame Up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 246 234
Measure Type: Count of Participants
Unit of Measure: Participants
238
  96.7%
227
  97.0%
15.Secondary Outcome
Title Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
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 is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.
Time Frame Up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 195 183
Measure Type: Count of Participants
Unit of Measure: Participants
192
  98.5%
178
  97.3%
16.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
Hide Description The number of all participants who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 246 234
Measure Type: Count of Participants
Unit of Measure: Participants
28
  11.4%
37
  15.8%
17.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
Hide Description The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all randomized participants with PD-L1 ≥1% CPS who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle.
Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Overall Number of Participants Analyzed 195 183
Measure Type: Count of Participants
Unit of Measure: Participants
24
  12.3%
30
  16.4%
Time Frame Up to approximately 27 months (Up to 90 days after last dose of study drug)
Adverse Event Reporting Description Safety Population: All participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as SAEs, with the exception of drug-related deaths, which are reported as "Malignant Neoplasm Progression".
 
Arm/Group Title Pembrolizumab Active Comparator
Hide Arm/Group Description Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle. Participants received methotrexate 40 mg/m^2 IV (may have been escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3-week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
All-Cause Mortality
Pembrolizumab Active Comparator
Affected / at Risk (%) Affected / at Risk (%)
Total   181/246 (73.58%)      207/234 (88.46%)    
Hide Serious Adverse Events
Pembrolizumab Active Comparator
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   110/246 (44.72%)      92/234 (39.32%)    
Blood and lymphatic system disorders     
Anaemia  1  5/246 (2.03%)  5 2/234 (0.85%)  2
Anaemia of malignant disease  1  1/246 (0.41%)  3 0/234 (0.00%)  0
Febrile neutropenia  1  0/246 (0.00%)  0 9/234 (3.85%)  9
Lymph node haemorrhage  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pancytopenia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Cardiac disorders     
Myocardial infarction  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pericardial effusion  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Endocrine disorders     
Hypercalcaemia of malignancy  1  3/246 (1.22%)  3 2/234 (0.85%)  2
Gastrointestinal disorders     
Abdominal pain upper  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Colitis  1  2/246 (0.81%)  2 1/234 (0.43%)  1
Constipation  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Diarrhoea  1  6/246 (2.44%)  8 2/234 (0.85%)  2
Dysphagia  1  4/246 (1.63%)  4 3/234 (1.28%)  3
Gastrointestinal haemorrhage  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Gastrointestinal inflammation  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Incarcerated inguinal hernia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Inguinal hernia  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Large intestine perforation  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Malignant dysphagia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Mouth haemorrhage  1  3/246 (1.22%)  3 3/234 (1.28%)  3
Nausea  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Oral discharge  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pneumoperitoneum  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Stomatitis  1  1/246 (0.41%)  1 3/234 (1.28%)  3
Upper gastrointestinal haemorrhage  1  0/246 (0.00%)  0 1/234 (0.43%)  1
General disorders     
Asthenia  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Death  1  5/246 (2.03%)  5 4/234 (1.71%)  4
Euthanasia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Face oedema  1  1/246 (0.41%)  1 1/234 (0.43%)  1
General physical health deterioration  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Ill-defined disorder  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Malaise  1  1/246 (0.41%)  1 2/234 (0.85%)  2
Performance status decreased  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pyrexia  1  1/246 (0.41%)  1 3/234 (1.28%)  3
Hepatobiliary disorders     
Autoimmune hepatitis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Cholelithiasis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Cirrhosis alcoholic  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Immune system disorders     
Anaphylactic reaction  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Hypersensitivity  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Infections and infestations     
Bronchitis  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Candida sepsis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Cellulitis  1  3/246 (1.22%)  4 0/234 (0.00%)  0
Clostridium difficile colitis  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Colonic abscess  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Disseminated tuberculosis  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Epiglottitis  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Herpes zoster  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Infected fistula  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Infection  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Infective exacerbation of chronic obstructive airways disease  1  1/246 (0.41%)  2 0/234 (0.00%)  0
Influenza  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Klebsiella infection  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Lower respiratory tract infection  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Lower respiratory tract infection bacterial  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Lung infection  1  1/246 (0.41%)  1 2/234 (0.85%)  3
Neutropenic sepsis  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Oral bacterial infection  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Oral candidiasis  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Pneumocystis jirovecii pneumonia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pneumonia  1  20/246 (8.13%)  21 16/234 (6.84%)  17
Pulmonary sepsis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Respiratory tract infection  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Sepsis  1  4/246 (1.63%)  4 3/234 (1.28%)  3
Septic shock  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Stoma site infection  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Subcutaneous abscess  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Upper respiratory tract infection  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Urinary tract infection  1  1/246 (0.41%)  1 2/234 (0.85%)  2
Urosepsis  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Wound infection  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Injury, poisoning and procedural complications     
Accidental overdose  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Alcohol poisoning  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Fall  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Femoral neck fracture  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Hip fracture  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Postoperative fever  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Procedural hypotension  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Spinal fracture  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Stoma site haemorrhage  1  0/246 (0.00%)  0 1/234 (0.43%)  2
Stoma site ulcer  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Subarachnoid haemorrhage  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Tracheostomy malfunction  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Investigations     
Blood creatinine increased  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Hepatic enzyme increased  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Neutrophil count decreased  1  0/246 (0.00%)  0 3/234 (1.28%)  5
Platelet count decreased  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Weight decreased  1  1/246 (0.41%)  1 0/234 (0.00%)  0
White blood cell count decreased  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Metabolism and nutrition disorders     
Decreased appetite  1  4/246 (1.63%)  4 0/234 (0.00%)  0
Dehydration  1  2/246 (0.81%)  2 3/234 (1.28%)  3
Diabetes mellitus inadequate control  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Hypercalcaemia  1  7/246 (2.85%)  7 0/234 (0.00%)  0
Hyponatraemia  1  3/246 (1.22%)  3 0/234 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Kyphosis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Muscular weakness  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Soft tissue haemorrhage  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Astrocytoma, low grade  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Basal cell carcinoma  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Colon cancer  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Infected neoplasm  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Malignant neoplasm progression  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Paraneoplastic syndrome  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Rectal cancer  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Tumour haemorrhage  1  9/246 (3.66%)  10 2/234 (0.85%)  4
Tumour pain  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Nervous system disorders     
Cerebrovascular accident  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Guillain-Barre syndrome  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Seizure  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Somnolence  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Spinal cord compression  1  2/246 (0.81%)  3 0/234 (0.00%)  0
Syncope  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Vocal cord paresis  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Psychiatric disorders     
Confusional state  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Delirium  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Renal and urinary disorders     
Acute kidney injury  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/246 (0.41%)  1 1/234 (0.43%)  1
Asphyxia  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Aspiration  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Chronic obstructive pulmonary disease  1  1/246 (0.41%)  2 1/234 (0.43%)  3
Dyspnoea  1  4/246 (1.63%)  4 1/234 (0.43%)  1
Eosinophilic pneumonia  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Epistaxis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Haemoptysis  1  2/246 (0.81%)  3 0/234 (0.00%)  0
Hypoxia  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Laryngeal obstruction  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Laryngeal stenosis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Lung disorder  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pharyngeal fistula  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Pleural effusion  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Pneumonia aspiration  1  6/246 (2.44%)  7 3/234 (1.28%)  3
Pneumonitis  1  6/246 (2.44%)  6 3/234 (1.28%)  3
Pneumothorax  1  0/246 (0.00%)  0 2/234 (0.85%)  2
Pulmonary embolism  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Respiratory disorder  1  0/246 (0.00%)  0 1/234 (0.43%)  2
Respiratory failure  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Respiratory tract haemorrhage  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Fungating wound  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Pruritus  1  0/246 (0.00%)  0 1/234 (0.43%)  1
Skin ulcer  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Stevens-Johnson syndrome  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Vascular disorders     
Angiodysplasia  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Deep vein thrombosis  1  1/246 (0.41%)  1 0/234 (0.00%)  0
Haemorrhage  1  2/246 (0.81%)  2 0/234 (0.00%)  0
Jugular vein thrombosis  1  0/246 (0.00%)  0 1/234 (0.43%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab Active Comparator
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   212/246 (86.18%)      210/234 (89.74%)    
Blood and lymphatic system disorders     
Anaemia  1  62/246 (25.20%)  77 51/234 (21.79%)  70
Endocrine disorders     
Hypothyroidism  1  37/246 (15.04%)  40 9/234 (3.85%)  9
Gastrointestinal disorders     
Abdominal pain  1  9/246 (3.66%)  9 12/234 (5.13%)  12
Constipation  1  43/246 (17.48%)  49 37/234 (15.81%)  43
Diarrhoea  1  36/246 (14.63%)  54 41/234 (17.52%)  50
Dry mouth  1  15/246 (6.10%)  15 6/234 (2.56%)  6
Dysphagia  1  21/246 (8.54%)  23 15/234 (6.41%)  16
Nausea  1  34/246 (13.82%)  43 44/234 (18.80%)  52
Stomatitis  1  7/246 (2.85%)  9 26/234 (11.11%)  34
Vomiting  1  23/246 (9.35%)  27 23/234 (9.83%)  34
General disorders     
Asthenia  1  37/246 (15.04%)  47 41/234 (17.52%)  52
Fatigue  1  48/246 (19.51%)  51 63/234 (26.92%)  81
Mucosal inflammation  1  17/246 (6.91%)  21 36/234 (15.38%)  51
Pyrexia  1  24/246 (9.76%)  38 25/234 (10.68%)  35
Investigations     
Aspartate aminotransferase increased  1  10/246 (4.07%)  10 13/234 (5.56%)  18
Neutrophil count decreased  1  4/246 (1.63%)  11 24/234 (10.26%)  29
Platelet count decreased  1  7/246 (2.85%)  7 13/234 (5.56%)  19
Weight decreased  1  21/246 (8.54%)  22 26/234 (11.11%)  26
White blood cell count decreased  1  2/246 (0.81%)  3 12/234 (5.13%)  15
Metabolism and nutrition disorders     
Decreased appetite  1  31/246 (12.60%)  37 43/234 (18.38%)  48
Hypercalcaemia  1  14/246 (5.69%)  16 13/234 (5.56%)  14
Hypokalaemia  1  23/246 (9.35%)  27 19/234 (8.12%)  21
Hypomagnesaemia  1  10/246 (4.07%)  11 20/234 (8.55%)  25
Hyponatraemia  1  12/246 (4.88%)  14 16/234 (6.84%)  17
Hypophosphataemia  1  15/246 (6.10%)  21 12/234 (5.13%)  14
Musculoskeletal and connective tissue disorders     
Arthralgia  1  19/246 (7.72%)  20 5/234 (2.14%)  6
Back pain  1  23/246 (9.35%)  24 8/234 (3.42%)  8
Neck pain  1  19/246 (7.72%)  19 17/234 (7.26%)  17
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  13/246 (5.28%)  13 7/234 (2.99%)  8
Nervous system disorders     
Headache  1  21/246 (8.54%)  25 22/234 (9.40%)  24
Psychiatric disorders     
Anxiety  1  13/246 (5.28%)  13 6/234 (2.56%)  6
Insomnia  1  22/246 (8.94%)  22 17/234 (7.26%)  17
Respiratory, thoracic and mediastinal disorders     
Cough  1  42/246 (17.07%)  47 36/234 (15.38%)  39
Dyspnoea  1  30/246 (12.20%)  32 26/234 (11.11%)  31
Haemoptysis  1  13/246 (5.28%)  15 6/234 (2.56%)  8
Productive cough  1  14/246 (5.69%)  14 5/234 (2.14%)  7
Skin and subcutaneous tissue disorders     
Alopecia  1  1/246 (0.41%)  1 27/234 (11.54%)  27
Dermatitis acneiform  1  0/246 (0.00%)  0 18/234 (7.69%)  28
Dry skin  1  4/246 (1.63%)  4 17/234 (7.26%)  19
Pruritus  1  18/246 (7.32%)  22 17/234 (7.26%)  40
Rash  1  25/246 (10.16%)  32 38/234 (16.24%)  81
Vascular disorders     
Hypotension  1  12/246 (4.88%)  12 12/234 (5.13%)  16
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The 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 Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02252042    
Other Study ID Numbers: 3475-040
2014-001749-26 ( EudraCT Number )
MK-3475-040 ( Other Identifier: Merck Protocol Number )
First Submitted: September 25, 2014
First Posted: September 29, 2014
Results First Submitted: May 4, 2018
Results First Posted: August 13, 2018
Last Update Posted: July 29, 2021