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Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)

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: NCT03635567
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Results First Posted : October 12, 2023
Last Update Posted : January 17, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cervical Cancer
Interventions Biological: Pembrolizumab
Drug: Paclitaxel
Drug: Cisplatin
Drug: Carboplatin
Biological: Bevacizumab
Drug: Placebo to pembrolizumab
Enrollment 617
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Period Title: Overall Study
Started 308 309
Treated 307 309
Received Second Course of Pembrolizumab 8 0
Completed 0 0
Not Completed 308 309
Reason Not Completed
Lost to Follow-up             0             2
Withdrawal by Subject             9             10
Ongoing in Study             125             76
Death             174             221
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy Total
Hide Arm/Group Description On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. Total of all reporting groups
Overall Number of Baseline Participants 308 309 617
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 308 participants 309 participants 617 participants
51.7  (11.9) 50.7  (12.7) 51.2  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
Female
308
 100.0%
309
 100.0%
617
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
Hispanic or Latino
109
  35.4%
121
  39.2%
230
  37.3%
Not Hispanic or Latino
193
  62.7%
184
  59.5%
377
  61.1%
Unknown or Not Reported
6
   1.9%
4
   1.3%
10
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
American Indian or Alaska Native
18
   5.8%
21
   6.8%
39
   6.3%
Asian
65
  21.1%
45
  14.6%
110
  17.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   1.3%
2
   0.6%
6
   1.0%
White
170
  55.2%
190
  61.5%
360
  58.3%
More than one race
32
  10.4%
34
  11.0%
66
  10.7%
Unknown or Not Reported
19
   6.2%
17
   5.5%
36
   5.8%
Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
PD-L1 CPS<1
35
  11.4%
34
  11.0%
69
  11.2%
1≤ PD-L1 CPS<10
115
  37.3%
116
  37.5%
231
  37.4%
PD-L1 CPS≥10
158
  51.3%
159
  51.5%
317
  51.4%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue. Randomization of participants in the study were stratified by their PD-L1 CPS at baseline (PD-L1 CPS<1, 1≤ PD-L1 CPS<10, or PD-L1 CPS≥10).
Metastatic at Initial Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
Yes
94
  30.5%
96
  31.1%
190
  30.8%
No
214
  69.5%
213
  68.9%
427
  69.2%
[1]
Measure Description: Randomization of participants was stratified by whether they were metastatic at initial diagnosis (Yes or No). Metastatic was defined as Stage IV based on the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) (2009).
Investigator Choice to Use Bevacizumab   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 309 participants 617 participants
Yes
196
  63.6%
193
  62.5%
389
  63.0%
No
112
  36.4%
116
  37.5%
228
  37.0%
[1]
Measure Description: Randomization of participants was stratified by the Investigator's choice for the participant to receive bevacizumab (Yes or No).
1.Primary Outcome
Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥1 is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 273 275
Median (95% Confidence Interval)
Unit of Measure: Months
10.5
(9.7 to 12.3)
8.2
(6.3 to 8.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (hazard ratio [HR]) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.47 to 0.71
Estimation Comments [Not Specified]
2.Primary Outcome
Title PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 308 309
Median (95% Confidence Interval)
Unit of Measure: Months
10.4
(9.1 to 12.2)
8.2
(6.4 to 8.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.50 to 0.74
Estimation Comments [Not Specified]
3.Primary Outcome
Title PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥10 is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 158 159
Median (95% Confidence Interval)
Unit of Measure: Months
10.4
(8.9 to 15.1)
8.1
(6.2 to 8.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.40 to 0.68
Estimation Comments [Not Specified]
4.Primary Outcome
Title Overall Survival (OS) in Participants With PD-L1 CPS ≥1
Hide Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥1 is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 273 275
Median (95% Confidence Interval)
Unit of Measure: Months
28.6
(22.1 to 38.0)
16.5
(14.5 to 20.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.49 to 0.74
Estimation Comments [Not Specified]
5.Primary Outcome
Title OS in All Participants
Hide Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 308 309
Median (95% Confidence Interval)
Unit of Measure: Months
26.4
(21.3 to 32.5)
16.8
(14.6 to 19.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value based on log-rank test provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.52 to 0.77
Estimation Comments [Not Specified]
6.Primary Outcome
Title OS in Participants With PD-L1 CPS ≥10
Hide Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥10 is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 158 159
Median (95% Confidence Interval)
Unit of Measure: Months
29.6 [1] 
(20.6 to NA)
17.4
(14.0 to 24.7)
[1]
NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison.
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.44 to 0.78
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Hide Description ORR was defined as the percentage of the participants in the analysis population who have 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, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 308 309
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
66.2
(60.7 to 71.5)
51.5
(45.7 to 57.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison was based on Miettinen & Nurminen method stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 14.9
Confidence Interval (2-Sided) 95%
7.4 to 22.3
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
Hide Description For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized who demonstrated CR or PR.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 204 159
Median (95% Confidence Interval)
Unit of Measure: Months
18.0
(10.5 to 32.3)
10.4
(8.3 to 13.3)
9.Secondary Outcome
Title Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS Rate was defined as the percentage of participants that were PFS event-free at Month 12. The PFS Rate per RECIST 1.1 as assessed by Investigator at Month 12 is presented.
Time Frame 12 months
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Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 308 309
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
44.7
(38.9 to 50.4)
33.1
(27.7 to 38.7)
10.Secondary Outcome
Title PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
Hide Description PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR is presented.
Time Frame Up to approximately 46 months
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Hide Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 308 309
Median (95% Confidence Interval)
Unit of Measure: Months
12.3
(10.3 to 17.9)
8.3
(8.1 to 9.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Chemotherapy, Placebo+Chemotherapy
Comments Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No formal hypothesis testing performed; nominal p-value provided for treatment comparison
Method Stratified Log-Rank
Comments Nominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.49 to 0.74
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is presented.
Time Frame Up to approximately 46 months
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Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 307 309
Measure Type: Number
Unit of Measure: Number of participants
305 307
12.Secondary Outcome
Title Number of Participants Who Experienced a Serious AE (SAE)
Hide Description An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented.
Time Frame Up to approximately 46 months
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Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 307 309
Measure Type: Number
Unit of Measure: Number of Participants
157 132
13.Secondary Outcome
Title Number of Participants Who Experienced an Immune-related AE (irAE)
Hide Description

AEs associated with pembrolizumab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. For this study irAEs included, but were not limited to: -Pneumonitis;

  • Diarrhea/Colitis;
  • Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin;
  • Type 1 diabetes mellitus or Hyperglycemia;
  • Hypophysitis;
  • Hyperthyroidism;
  • Hypothyroidism;
  • Nephritis and Renal dysfunction; and
  • Myocarditis. The number of participants who experienced an irAE is presented.
Time Frame Up to approximately 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 307 309
Measure Type: Number
Unit of Measure: Number of Participants
106 51
14.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 307 309
Measure Type: Number
Unit of Measure: Number of Participants
125 91
15.Secondary Outcome
Title Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
Hide Description The EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. Participant responses to "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Raw scores are standardized with linear transformation so that scores range from 0-100. A higher combined score indicates a better overall health status. Participant post-baseline scores were classified based on change from baseline, "Improved": a ≥10-point improvement in score and confirmed by the next visit; "Stable": a ≥10-point increase or <10-point change in score OR a <10-point change in score and a ≥10-point increase in score at the next visit; or "Deteriorated": a ≥10-point deterioration in score when the criteria for improvement/stability weren't met. Participants who didn't meet "Improved", "Stable", or "Deteriorated" criteria reported as "Other".
Time Frame Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months
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Hide Analysis Population Description
Per protocol, all randomized participants who received at least one dose of study treatment and completed at least one EORTC QLQ-C30 assessment were analyzed. Participants with no EORTC QLQ-C30 assessment were not included in the analysis.
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Hide Arm/Group Description:
On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed 279 282
Measure Type: Number
Unit of Measure: Number of Participants
Improved 122 86
Stable 106 139
Deteriorated 42 48
Other 9 9
Time Frame Up to approximately 46 months
Adverse Event Reporting Description Serious and Other adverse events (AEs) included all participants who received ≥1 dose of study drug. All-Cause Mortality included all randomized participants. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs. Data are reported by treatment received.
 
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy Pembrolizumab (Second Course)
Hide Arm/Group Description On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
All-Cause Mortality
Pembrolizumab+Chemotherapy Placebo+Chemotherapy Pembrolizumab (Second Course)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   178/308 (57.79%)      228/309 (73.79%)      0/8 (0.00%)    
Hide Serious Adverse Events
Pembrolizumab+Chemotherapy Placebo+Chemotherapy Pembrolizumab (Second Course)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   157/307 (51.14%)      132/309 (42.72%)      3/8 (37.50%)    
Blood and lymphatic system disorders       
Anaemia  1  14/307 (4.56%)  14 12/309 (3.88%)  14 0/8 (0.00%)  0
Bicytopenia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Febrile neutropenia  1  21/307 (6.84%)  25 13/309 (4.21%)  14 0/8 (0.00%)  0
Leukopenia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Lymphadenitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Neutropenia  1  4/307 (1.30%)  5 3/309 (0.97%)  3 0/8 (0.00%)  0
Pancytopenia  1  2/307 (0.65%)  2 3/309 (0.97%)  3 0/8 (0.00%)  0
Thrombocytopenia  1  3/307 (0.98%)  3 2/309 (0.65%)  3 0/8 (0.00%)  0
Cardiac disorders       
Acute myocardial infarction  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Atrial fibrillation  1  4/307 (1.30%)  4 1/309 (0.32%)  1 0/8 (0.00%)  0
Bundle branch block  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Cardiac arrest  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Cardiac failure congestive  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Mitral valve stenosis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Myocardial infarction  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Myocarditis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Stress cardiomyopathy  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Supraventricular tachycardia  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Endocrine disorders       
Adrenal insufficiency  1  3/307 (0.98%)  3 0/309 (0.00%)  0 0/8 (0.00%)  0
Hyperthyroidism  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Hypophysitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Eye disorders       
Optic neuropathy  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  2/307 (0.65%)  2 3/309 (0.97%)  3 0/8 (0.00%)  0
Abdominal pain lower  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Abdominal pain upper  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Anal fistula  1  1/307 (0.33%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Anal haemorrhage  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Anal ulcer  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Colitis  1  3/307 (0.98%)  3 3/309 (0.97%)  3 0/8 (0.00%)  0
Constipation  1  0/307 (0.00%)  0 2/309 (0.65%)  2 0/8 (0.00%)  0
Diarrhoea  1  5/307 (1.63%)  5 2/309 (0.65%)  2 0/8 (0.00%)  0
Duodenal perforation  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Enterocolitis  1  1/307 (0.33%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Enterovesical fistula  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Gastric haemorrhage  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Gastric ulcer  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Gastritis  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Gingival bleeding  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Ileus  1  0/307 (0.00%)  0 1/309 (0.32%)  4 0/8 (0.00%)  0
Immune-mediated enterocolitis  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Intestinal obstruction  1  3/307 (0.98%)  3 2/309 (0.65%)  2 0/8 (0.00%)  0
Intestinal perforation  1  2/307 (0.65%)  2 1/309 (0.32%)  1 0/8 (0.00%)  0
Intestinal pseudo-obstruction  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Large intestinal obstruction  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Large intestine perforation  1  0/307 (0.00%)  0 2/309 (0.65%)  2 0/8 (0.00%)  0
Nausea  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Pancreatitis acute  1  2/307 (0.65%)  2 1/309 (0.32%)  1 0/8 (0.00%)  0
Proctitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Rectal haemorrhage  1  3/307 (0.98%)  3 1/309 (0.32%)  1 0/8 (0.00%)  0
Rectal perforation  1  2/307 (0.65%)  2 1/309 (0.32%)  1 0/8 (0.00%)  0
Small intestinal obstruction  1  0/307 (0.00%)  0 3/309 (0.97%)  3 0/8 (0.00%)  0
Small intestinal perforation  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Subileus  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/307 (0.00%)  0 2/309 (0.65%)  2 0/8 (0.00%)  0
Volvulus  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Vomiting  1  3/307 (0.98%)  3 2/309 (0.65%)  2 0/8 (0.00%)  0
General disorders       
Asthenia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Chest pain  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Death  1  3/307 (0.98%)  3 3/309 (0.97%)  3 0/8 (0.00%)  0
Fatigue  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
General physical health deterioration  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Infusion site extravasation  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Malaise  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Medical device site laceration  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Pseudocyst  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Pyrexia  1  9/307 (2.93%)  9 5/309 (1.62%)  5 0/8 (0.00%)  0
Hepatobiliary disorders       
Autoimmune hepatitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Biliary obstruction  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Cholecystitis acute  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Cholelithiasis  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Drug-induced liver injury  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Hepatobiliary disease  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Hepatotoxicity  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Immune-mediated cholangitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Immune-mediated hepatitis  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Immune system disorders       
Anaphylactic reaction  1  1/307 (0.33%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Anaphylactic shock  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Contrast media allergy  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Drug hypersensitivity  1  0/307 (0.00%)  0 3/309 (0.97%)  3 0/8 (0.00%)  0
Hypersensitivity  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
Infections and infestations       
Abdominal sepsis  1  0/307 (0.00%)  0 2/309 (0.65%)  2 0/8 (0.00%)  0
Abdominal wall abscess  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Abscess  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Acute hepatitis B  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Anal abscess  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Bacteraemia  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Bronchitis  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
COVID-19  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
COVID-19 pneumonia  1  1/307 (0.33%)  1 3/309 (0.97%)  3 0/8 (0.00%)  0
Cellulitis  1  1/307 (0.33%)  2 2/309 (0.65%)  2 0/8 (0.00%)  0
Clostridium difficile colitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Cystitis  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Cytomegalovirus infection  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Device related infection  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Diverticulitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Empyema  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Erysipelas  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Fournier's gangrene  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Groin abscess  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Herpes zoster  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Herpes zoster meningoradiculitis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Infected fistula  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Infected lymphocele  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Infection  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Influenza  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Lower respiratory tract infection  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Pelvic infection  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Peritonitis  1  2/307 (0.65%)  2 1/309 (0.32%)  1 0/8 (0.00%)  0
Pneumonia  1  1/307 (0.33%)  1 7/309 (2.27%)  7 0/8 (0.00%)  0
Psoas abscess  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Pulmonary sepsis  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Pyelonephritis  1  4/307 (1.30%)  4 2/309 (0.65%)  4 0/8 (0.00%)  0
Pyelonephritis acute  1  2/307 (0.65%)  2 3/309 (0.97%)  3 0/8 (0.00%)  0
Pyometra  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Sepsis  1  8/307 (2.61%)  8 5/309 (1.62%)  5 0/8 (0.00%)  0
Septic shock  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Staphylococcal bacteraemia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Urinary tract infection  1  16/307 (5.21%)  17 20/309 (6.47%)  23 1/8 (12.50%)  2
Urosepsis  1  2/307 (0.65%)  2 4/309 (1.29%)  5 0/8 (0.00%)  0
Vascular device infection  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Wound infection  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Injury, poisoning and procedural complications       
Ankle fracture  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Cystitis radiation  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Fall  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Femoral neck fracture  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Femur fracture  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
Fibula fracture  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Foot fracture  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Gastroenteritis radiation  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Gastrointestinal stoma complication  1  0/307 (0.00%)  0 1/309 (0.32%)  2 0/8 (0.00%)  0
Hip fracture  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Humerus fracture  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Infusion related reaction  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Pelvic fracture  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Post procedural urine leak  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Procedural pneumothorax  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Radiation proctitis  1  4/307 (1.30%)  6 2/309 (0.65%)  2 0/8 (0.00%)  0
Stoma site haemorrhage  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Tibia fracture  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Urinary tract stoma complication  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
Wrist fracture  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Aspartate aminotransferase increased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Blood alkaline phosphatase increased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Blood pressure increased  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Liver function test increased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Neutrophil count decreased  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Platelet count decreased  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Urine output decreased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Weight decreased  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Metabolism and nutrition disorders       
Cachexia  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Decreased appetite  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Dehydration  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Diabetic ketoacidosis  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Electrolyte imbalance  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Hypocalcaemia  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Hypokalaemia  1  2/307 (0.65%)  2 2/309 (0.65%)  2 0/8 (0.00%)  0
Hypovolaemia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Autoimmune myositis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Back pain  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Muscular weakness  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Myalgia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Myositis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Osteoporosis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Pain in extremity  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Cervix carcinoma  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Diffuse large B-cell lymphoma  1  0/307 (0.00%)  0 0/309 (0.00%)  0 1/8 (12.50%)  1
Endometrial adenocarcinoma  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Metastases to central nervous system  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Ovarian cancer recurrent  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Tumour haemorrhage  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Nervous system disorders       
Cerebellar infarction  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Cerebral ischaemia  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Cerebrovascular accident  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Embolic stroke  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Encephalitis autoimmune  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Headache  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Hemiparesis  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Hypoaesthesia  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Idiopathic intracranial hypertension  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Ischaemic stroke  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Paraesthesia  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Peripheral motor neuropathy  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Peripheral sensorimotor neuropathy  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Peripheral sensory neuropathy  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Seizure  1  3/307 (0.98%)  3 0/309 (0.00%)  0 0/8 (0.00%)  0
Syncope  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Transient ischaemic attack  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Product Issues       
Device dislocation  1  2/307 (0.65%)  2 2/309 (0.65%)  2 0/8 (0.00%)  0
Device occlusion  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Stent malfunction  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Psychiatric disorders       
Confusional state  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Delirium  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  11/307 (3.58%)  13 5/309 (1.62%)  6 0/8 (0.00%)  0
Bladder diverticulum  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Haematuria  1  4/307 (1.30%)  5 4/309 (1.29%)  4 0/8 (0.00%)  0
Hydronephrosis  1  4/307 (1.30%)  4 4/309 (1.29%)  4 1/8 (12.50%)  1
Nephrolithiasis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Nephropathy  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Postrenal failure  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Renal failure  1  1/307 (0.33%)  1 3/309 (0.97%)  3 0/8 (0.00%)  0
Ureteric stenosis  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Urethral fistula  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Urinary tract obstruction  1  1/307 (0.33%)  1 3/309 (0.97%)  3 0/8 (0.00%)  0
Urinoma  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Urogenital fistula  1  4/307 (1.30%)  4 2/309 (0.65%)  2 0/8 (0.00%)  0
Reproductive system and breast disorders       
Abnormal uterine bleeding  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Female genital tract fistula  1  8/307 (2.61%)  8 10/309 (3.24%)  10 1/8 (12.50%)  1
Heavy menstrual bleeding  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Intermenstrual bleeding  1  2/307 (0.65%)  2 1/309 (0.32%)  1 0/8 (0.00%)  0
Pelvic pain  1  1/307 (0.33%)  1 3/309 (0.97%)  3 0/8 (0.00%)  0
Uterine haemorrhage  1  3/307 (0.98%)  3 1/309 (0.32%)  1 0/8 (0.00%)  0
Vaginal fistula  1  1/307 (0.33%)  1 2/309 (0.65%)  2 0/8 (0.00%)  0
Vaginal haemorrhage  1  5/307 (1.63%)  5 4/309 (1.29%)  5 0/8 (0.00%)  0
Vulval ulceration  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Dyspnoea  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Epistaxis  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Oropharyngeal pain  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Pleurisy  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Pneumonitis  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Pneumothorax  1  1/307 (0.33%)  1 1/309 (0.32%)  1 0/8 (0.00%)  0
Pulmonary embolism  1  4/307 (1.30%)  4 6/309 (1.94%)  6 0/8 (0.00%)  0
Pulmonary haemorrhage  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis allergic  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Drug eruption  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Rash erythematous  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Rash maculo-papular  1  3/307 (0.98%)  3 0/309 (0.00%)  0 0/8 (0.00%)  0
Skin ulcer  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Vascular disorders       
Deep vein thrombosis  1  4/307 (1.30%)  4 1/309 (0.32%)  1 0/8 (0.00%)  0
Embolism  1  2/307 (0.65%)  2 2/309 (0.65%)  2 0/8 (0.00%)  0
Hypertension  1  0/307 (0.00%)  0 3/309 (0.97%)  3 0/8 (0.00%)  0
Hypertensive urgency  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
Orthostatic hypotension  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Shock haemorrhagic  1  2/307 (0.65%)  2 0/309 (0.00%)  0 0/8 (0.00%)  0
Subclavian vein thrombosis  1  0/307 (0.00%)  0 1/309 (0.32%)  1 0/8 (0.00%)  0
Vena cava embolism  1  1/307 (0.33%)  1 0/309 (0.00%)  0 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA 25.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab+Chemotherapy Placebo+Chemotherapy Pembrolizumab (Second Course)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   298/307 (97.07%)      299/309 (96.76%)      5/8 (62.50%)    
Blood and lymphatic system disorders       
Anaemia  1  181/307 (58.96%)  263 159/309 (51.46%)  247 1/8 (12.50%)  1
Leukopenia  1  40/307 (13.03%)  72 33/309 (10.68%)  55 1/8 (12.50%)  1
Lymphopenia  1  15/307 (4.89%)  29 7/309 (2.27%)  7 1/8 (12.50%)  1
Neutropenia  1  71/307 (23.13%)  143 58/309 (18.77%)  115 0/8 (0.00%)  0
Thrombocytopenia  1  60/307 (19.54%)  94 60/309 (19.42%)  101 0/8 (0.00%)  0
Ear and labyrinth disorders       
Ear discomfort  1  0/307 (0.00%)  0 2/309 (0.65%)  2 1/8 (12.50%)  1
Endocrine disorders       
Hyperthyroidism  1  25/307 (8.14%)  27 9/309 (2.91%)  10 0/8 (0.00%)  0
Hypothyroidism  1  59/307 (19.22%)  64 31/309 (10.03%)  33 0/8 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  49/307 (15.96%)  64 51/309 (16.50%)  77 0/8 (0.00%)  0
Abdominal pain lower  1  16/307 (5.21%)  18 12/309 (3.88%)  13 0/8 (0.00%)  0
Abdominal pain upper  1  29/307 (9.45%)  42 30/309 (9.71%)  40 0/8 (0.00%)  0
Constipation  1  89/307 (28.99%)  141 101/309 (32.69%)  146 0/8 (0.00%)  0
Diarrhoea  1  111/307 (36.16%)  201 93/309 (30.10%)  173 1/8 (12.50%)  1
Dyspepsia  1  20/307 (6.51%)  23 15/309 (4.85%)  19 0/8 (0.00%)  0
Gastrooesophageal reflux disease  1  11/307 (3.58%)  11 13/309 (4.21%)  14 1/8 (12.50%)  1
Nausea  1  122/307 (39.74%)  264 135/309 (43.69%)  287 0/8 (0.00%)  0
Rectal haemorrhage  1  16/307 (5.21%)  26 15/309 (4.85%)  20 0/8 (0.00%)  0
Stomatitis  1  22/307 (7.17%)  26 21/309 (6.80%)  27 0/8 (0.00%)  0
Vomiting  1  80/307 (26.06%)  126 84/309 (27.18%)  141 0/8 (0.00%)  0
General disorders       
Asthenia  1  63/307 (20.52%)  121 66/309 (21.36%)  128 0/8 (0.00%)  0
Fatigue  1  89/307 (28.99%)  149 85/309 (27.51%)  150 0/8 (0.00%)  0
Mucosal inflammation  1  23/307 (7.49%)  31 10/309 (3.24%)  14 0/8 (0.00%)  0
Oedema peripheral  1  31/307 (10.10%)  37 30/309 (9.71%)  36 0/8 (0.00%)  0
Pyrexia  1  51/307 (16.61%)  77 44/309 (14.24%)  59 0/8 (0.00%)  0
Infections and infestations       
Nasopharyngitis  1  19/307 (6.19%)  25 10/309 (3.24%)  12 1/8 (12.50%)  1
Upper respiratory tract infection  1  13/307 (4.23%)  18 16/309 (5.18%)  21 0/8 (0.00%)  0
Urinary tract infection  1  67/307 (21.82%)  119 72/309 (23.30%)  107 0/8 (0.00%)  0
Injury, poisoning and procedural complications       
Gastroenteritis radiation  1  7/307 (2.28%)  7 3/309 (0.97%)  3 1/8 (12.50%)  1
Infusion related reaction  1  17/307 (5.54%)  24 12/309 (3.88%)  17 0/8 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  45/307 (14.66%)  67 28/309 (9.06%)  36 1/8 (12.50%)  1
Aspartate aminotransferase increased  1  34/307 (11.07%)  56 23/309 (7.44%)  30 1/8 (12.50%)  1
Blood alkaline phosphatase increased  1  27/307 (8.79%)  33 18/309 (5.83%)  20 1/8 (12.50%)  1
Blood creatinine increased  1  28/307 (9.12%)  43 34/309 (11.00%)  42 0/8 (0.00%)  0
Neutrophil count decreased  1  56/307 (18.24%)  152 48/309 (15.53%)  142 0/8 (0.00%)  0
Platelet count decreased  1  49/307 (15.96%)  99 42/309 (13.59%)  68 0/8 (0.00%)  0
Weight decreased  1  33/307 (10.75%)  33 37/309 (11.97%)  38 0/8 (0.00%)  0
White blood cell count decreased  1  37/307 (12.05%)  109 22/309 (7.12%)  62 0/8 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  62/307 (20.20%)  95 52/309 (16.83%)  76 0/8 (0.00%)  0
Hyperglycaemia  1  14/307 (4.56%)  20 19/309 (6.15%)  28 1/8 (12.50%)  1
Hypoalbuminaemia  1  17/307 (5.54%)  18 11/309 (3.56%)  11 1/8 (12.50%)  1
Hypokalaemia  1  30/307 (9.77%)  43 29/309 (9.39%)  34 0/8 (0.00%)  0
Hypomagnesaemia  1  27/307 (8.79%)  38 19/309 (6.15%)  31 0/8 (0.00%)  0
Hyponatraemia  1  20/307 (6.51%)  25 15/309 (4.85%)  16 0/8 (0.00%)  0
Hypoproteinaemia  1  3/307 (0.98%)  4 0/309 (0.00%)  0 1/8 (12.50%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  82/307 (26.71%)  128 77/309 (24.92%)  124 0/8 (0.00%)  0
Back pain  1  44/307 (14.33%)  55 46/309 (14.89%)  61 0/8 (0.00%)  0
Bone pain  1  21/307 (6.84%)  22 18/309 (5.83%)  22 0/8 (0.00%)  0
Myalgia  1  57/307 (18.57%)  98 61/309 (19.74%)  115 1/8 (12.50%)  1
Pain in extremity  1  37/307 (12.05%)  58 27/309 (8.74%)  51 0/8 (0.00%)  0
Nervous system disorders       
Dizziness  1  22/307 (7.17%)  27 25/309 (8.09%)  32 0/8 (0.00%)  0
Dysgeusia  1  15/307 (4.89%)  17 20/309 (6.47%)  24 0/8 (0.00%)  0
Headache  1  50/307 (16.29%)  76 57/309 (18.45%)  98 0/8 (0.00%)  0
Neuropathy peripheral  1  81/307 (26.38%)  106 80/309 (25.89%)  97 0/8 (0.00%)  0
Paraesthesia  1  28/307 (9.12%)  38 26/309 (8.41%)  34 0/8 (0.00%)  0
Peripheral sensory neuropathy  1  70/307 (22.80%)  81 78/309 (25.24%)  88 0/8 (0.00%)  0
Psychiatric disorders       
Insomnia  1  34/307 (11.07%)  35 27/309 (8.74%)  29 1/8 (12.50%)  1
Renal and urinary disorders       
Dysuria  1  21/307 (6.84%)  26 23/309 (7.44%)  29 0/8 (0.00%)  0
Haematuria  1  20/307 (6.51%)  25 15/309 (4.85%)  20 0/8 (0.00%)  0
Incontinence  1  3/307 (0.98%)  4 0/309 (0.00%)  0 1/8 (12.50%)  1
Leukocyturia  1  5/307 (1.63%)  8 1/309 (0.32%)  1 1/8 (12.50%)  1
Proteinuria  1  51/307 (16.61%)  79 31/309 (10.03%)  48 0/8 (0.00%)  0
Reproductive system and breast disorders       
Pelvic pain  1  16/307 (5.21%)  18 33/309 (10.68%)  39 0/8 (0.00%)  0
Vaginal discharge  1  17/307 (5.54%)  18 24/309 (7.77%)  26 0/8 (0.00%)  0
Vaginal haemorrhage  1  25/307 (8.14%)  40 32/309 (10.36%)  40 1/8 (12.50%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma  1  2/307 (0.65%)  2 0/309 (0.00%)  0 1/8 (12.50%)  1
Cough  1  40/307 (13.03%)  48 32/309 (10.36%)  40 1/8 (12.50%)  1
Dyspnoea  1  22/307 (7.17%)  28 30/309 (9.71%)  34 0/8 (0.00%)  0
Epistaxis  1  31/307 (10.10%)  53 43/309 (13.92%)  64 0/8 (0.00%)  0
Oropharyngeal discomfort  1  0/307 (0.00%)  0 0/309 (0.00%)  0 1/8 (12.50%)  1
Skin and subcutaneous tissue disorders       
Alopecia  1  173/307 (56.35%)  173 179/309 (57.93%)  181 0/8 (0.00%)  0
Dry skin  1  18/307 (5.86%)  18 9/309 (2.91%)  10 0/8 (0.00%)  0
Pruritus  1  40/307 (13.03%)  58 26/309 (8.41%)  39 0/8 (0.00%)  0
Rash  1  47/307 (15.31%)  66 36/309 (11.65%)  47 2/8 (25.00%)  2
Rash maculo-papular  1  16/307 (5.21%)  20 9/309 (2.91%)  13 1/8 (12.50%)  2
Vascular disorders       
Hypertension  1  79/307 (25.73%)  114 70/309 (22.65%)  100 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA 25.0
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 will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT03635567    
Other Study ID Numbers: 3475-826
MK-3475-826 ( Other Identifier: Merck )
KEYNOTE-826 ( Other Identifier: Merck )
184183 ( Registry Identifier: JAPAC-CTI )
2018-001440-53 ( EudraCT Number )
First Submitted: August 15, 2018
First Posted: August 17, 2018
Results First Submitted: September 20, 2023
Results First Posted: October 12, 2023
Last Update Posted: January 17, 2024