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Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)

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ClinicalTrials.gov Identifier: NCT02819518
Recruitment Status : Completed
First Posted : June 30, 2016
Results First Posted : July 5, 2022
Last Update Posted : November 9, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Triple Negative Breast Cancer (TNBC)
Interventions Biological: Pembrolizumab
Drug: Nab-paclitaxel
Drug: Paclitaxel
Drug: Gemcitabine
Drug: Carboplatin
Drug: Normale Saline Solution
Enrollment 882
Recruitment Details  
Pre-assignment Details 35 participants were randomized to Part 1 (Safety Run-in) of the study, and 847 participants were randomized in Part 2 (phase 3) of the study. Eight participants randomized to the Part 2: Pembrolizumab + Chemotherapy arm received a second course of pembrolizumab at the investigator's discretion. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures respectively.
Arm/Group Title Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to ~1 year). Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle
Period Title: Overall Study
Started 11 14 10 566 281
Completed 0 0 0 0 0
Not Completed 11 14 10 566 281
Reason Not Completed
Death             9             11             9             447             233
Withdrawal by Subject             0             0             0             21             6
Ongoing in Study             2             3             1             98             42
Arm/Group Title Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to ~1 year). Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Total of all reporting groups
Overall Number of Baseline Participants 11 14 10 566 281 882
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
54.6  (13.5) 60.4  (15.3) 59.6  (11.7) 53.5  (12.7) 53.0  (12.7) 53.5  (12.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
Female
11
 100.0%
14
 100.0%
10
 100.0%
566
 100.0%
281
 100.0%
882
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
Hispanic or Latino
1
   9.1%
0
   0.0%
0
   0.0%
116
  20.5%
48
  17.1%
165
  18.7%
Not Hispanic or Latino
9
  81.8%
14
 100.0%
10
 100.0%
423
  74.7%
218
  77.6%
674
  76.4%
Unknown or Not Reported
1
   9.1%
0
   0.0%
0
   0.0%
27
   4.8%
15
   5.3%
43
   4.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
11
   1.9%
1
   0.4%
12
   1.4%
Asian
4
  36.4%
7
  50.0%
4
  40.0%
123
  21.7%
52
  18.5%
190
  21.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   9.1%
0
   0.0%
0
   0.0%
20
   3.5%
17
   6.0%
38
   4.3%
White
6
  54.5%
7
  50.0%
6
  60.0%
384
  67.8%
195
  69.4%
598
  67.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
11
   1.9%
8
   2.8%
19
   2.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
17
   3.0%
8
   2.8%
25
   2.8%
Programmed Cell Death Ligand 1 (PD-L1) Status (Combined Positive Score [CPS] Cutoff of 1)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
PD-L1 CPS ≥1
8
  72.7%
12
  85.7%
7
  70.0%
425
  75.1%
211
  75.1%
663
  75.2%
PD-L1 CPS <1
3
  27.3%
2
  14.3%
3
  30.0%
141
  24.9%
70
  24.9%
219
  24.8%
[1]
Measure Description: PD-L1 protein expression in triple-negative breast cancer (TNBC) is determined by using CPS, which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100. The number of participants with PD-L1 Status CPS<1 and CPS≥1 at baseline is presented.
PD-L1 Status (CPS Cutoff of 10)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 14 participants 10 participants 566 participants 281 participants 882 participants
PD-L1 CPS ≥10
1
   9.1%
9
  64.3%
4
  40.0%
220
  38.9%
103
  36.7%
337
  38.2%
PD-L1 CPS <10
10
  90.9%
5
  35.7%
6
  60.0%
346
  61.1%
178
  63.3%
545
  61.8%
[1]
Measure Description: PD-L1 protein expression in TNBC is determined by using CPS, which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100. The number of participants with PD-L1 Status CPS<10 and CPS≥10 at baseline is presented.
1.Primary Outcome
Title Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants
Hide Description An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame Up to approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.
Arm/Group Title Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 13 10 11
Measure Type: Number
Unit of Measure: Percentage of Participants
100.0 100.0 100.0
2.Primary Outcome
Title Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants
Hide Description An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame Up to approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.
Arm/Group Title Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 13 10 11
Measure Type: Number
Unit of Measure: Percentage of Participants
38.5 50.0 27.3
3.Primary Outcome
Title Part 2: Progression-Free Survival (PFS) - All Participants
Hide Description Progression-free survival was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by blinded independent central review (BICR) 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 566 281
Median (95% Confidence Interval)
Unit of Measure: Months
7.5
(6.3 to 7.7)
5.6
(5.4 to 7.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0120
Comments One-sided p-value based on log-rank test stratified by chemotherapy (taxane versus [vs] gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs. no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.70 to 0.98
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
4.Primary Outcome
Title Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors
Hide Description Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by BICR 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 425 211
Median (95% Confidence Interval)
Unit of Measure: Months
7.6
(6.6 to 8.0)
5.6
(5.4 to 7.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.62 to 0.91
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
5.Primary Outcome
Title Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors
Hide Description Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by BICR 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 220 103
Median (95% Confidence Interval)
Unit of Measure: Months
9.7
(7.6 to 11.3)
5.6
(5.3 to 7.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.50 to 0.88
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
6.Primary Outcome
Title Part 2: Overall Survival (OS) - All Participants
Hide Description Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 566 281
Median (95% Confidence Interval)
Unit of Measure: Months
17.2
(15.3 to 19.0)
15.5
(13.9 to 17.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0797
Comments One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.76 to 1.05
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
7.Primary Outcome
Title Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors
Hide Description Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 425 211
Median (95% Confidence Interval)
Unit of Measure: Months
17.6
(15.5 to 19.5)
16.0
(12.8 to 17.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0563
Comments One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.72 to 1.04
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
8.Primary Outcome
Title Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors
Hide Description Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 220 103
Median (95% Confidence Interval)
Unit of Measure: Months
23.0
(19.0 to 26.3)
16.1
(12.6 to 18.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0093
Comments One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.55 to 0.95
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.
9.Secondary Outcome
Title Part 2: Objective Response Rate (ORR) - All Participants
Hide Description Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 566 281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
40.8
(36.7 to 45.0)
37.0
(31.4 to 42.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1413
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in ORR (%) vs. Control
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-3.2 to 10.6
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
10.Secondary Outcome
Title Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors
Hide Description Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 425 211
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
44.9
(40.1 to 49.8)
38.9
(32.2 to 45.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0725
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in ORR (%) vs. Control
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-2.1 to 14.0
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
11.Secondary Outcome
Title Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors
Hide Description Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 220 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
52.7
(45.9 to 59.5)
40.8
(31.2 to 50.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0213
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in ORR(%) vs. Control
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
0.4 to 23.4
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
12.Secondary Outcome
Title Part 2: Duration of Response (DOR) - All Participants
Hide Description For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants, regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 231 104
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
6.5 [2] 
(1.5 to NA)
[1]
NA indicates median, upper limit, lower limit not reached due to insufficient number of responding participants with relapse
[2]
NA indicates upper limit not reached due to insufficient number of responding participants with relapse
13.Secondary Outcome
Title Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors
Hide Description For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-LI CPS ≥1 tumors regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 191 82
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
6.8 [2] 
(1.5 to NA)
[1]
NA indicates median, upper limit, lower limit not reached due to insufficient number of responding participants with relapse
[2]
NA indicates upper limit not reached due to insufficient number of responding participants with relapse
14.Secondary Outcome
Title Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors
Hide Description For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-LI CPS ≥10 tumors regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 116 42
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
7.3 [2] 
(1.5 to NA)
[1]
NA indicates median, upper limit, lower limit not reached due to insufficient number of responding participants with relapse
[2]
NA indicates upper limit not reached due to insufficient number of responding participants with relapse
15.Secondary Outcome
Title Part 2: Disease Control Rate (DCR) - All Participants
Hide Description Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 566 281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
56.0
(51.8 to 60.1)
51.2
(45.2 to 57.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0966
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in DCR (%) vs. control
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-2.4 to 11.8
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).
16.Secondary Outcome
Title Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors
Hide Description Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 425 211
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
58.6
(53.7 to 63.3)
53.6
(46.6 to 60.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1164
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in DCR (%) vs. Control
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-3.2 to 13.1
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).
17.Secondary Outcome
Title Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors
Hide Description Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 220 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
65.0
(58.3 to 71.3)
54.4
(44.3 to 64.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Pembrolizumab + Chemotherapy, Part 2: Placebo + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0327
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in DCR (%) vs. Control
Estimated Value 10.8
Confidence Interval (2-Sided) 95%
-0.7 to 22.3
Estimation Comments Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).
18.Secondary Outcome
Title Part 2: Percentage of Participants Who Experienced an AE- All Participants
Hide Description An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame Up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 562 281
Measure Type: Number
Unit of Measure: Percentage of Participants
98.6 98.2
19.Secondary Outcome
Title Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants
Hide Description An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame Up to approximately 52 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 562 281
Measure Type: Number
Unit of Measure: Percentage of Participants
20.5 13.5
20.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants
Hide Description The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "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) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame Baseline and Week 15
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Hide Analysis Population Description
All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 554 278
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-3.52
(-5.61 to -1.42)
-2.15
(-4.97 to 0.67)
21.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors
Hide Description The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "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) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame Baseline and Week 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 415 208
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-3.92
(-6.42 to -1.44)
-3.15
(-6.54 to 0.24)
22.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors
Hide Description The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "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) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame Baseline and Week 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 216 100
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-2.69
(-5.86 to 0.48)
-0.88
(-5.41 to 3.64)
23.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants
Hide Description EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame Baseline and Week 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 554 278
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
12.50
(10.84 to 14.15)
12.36
(10.06 to 14.65)
24.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors
Hide Description EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame Baseline and Week 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 415 208
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
13.00
(11.08 to 14.91)
11.86
(9.17 to 14.55)
25.Secondary Outcome
Title Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors
Hide Description EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame Baseline and Week 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.
Arm/Group Title Part 2: Pembrolizumab + Chemotherapy Part 2: Placebo + Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Overall Number of Participants Analyzed 216 100
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
13.56
(10.88 to 16.23)
13.26
(9.28 to 17.25)
Time Frame Up to approximately 53 months (database cutoff date: 15JUN2021)
Adverse Event Reporting Description The population for all cause mortality includes all participants in the treatment arm to which they were randomly assigned. The population for AEs includes all participants who received at least 1 dose of study intervention in the arm of the study intervention received. 4 participants assigned to the Part 1: pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.
 
Arm/Group Title Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy (First Course) Part 2: Pembrolizumab + Chemotherapy (Second Course) Part 2: Placebo + Chemotherapy
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. 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. Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
All-Cause Mortality
Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy (First Course) Part 2: Pembrolizumab + Chemotherapy (Second Course) Part 2: Placebo + Chemotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/11 (81.82%)      11/14 (78.57%)      9/10 (90.00%)      459/566 (81.10%)      1/8 (12.50%)      238/281 (84.70%)    
Hide Serious Adverse Events
Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy (First Course) Part 2: Pembrolizumab + Chemotherapy (Second Course) Part 2: Placebo + Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/13 (23.08%)      4/10 (40.00%)      9/11 (81.82%)      169/562 (30.07%)      2/8 (25.00%)      67/281 (23.84%)    
Blood and lymphatic system disorders             
Anaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 2/11 (18.18%)  3 11/562 (1.96%)  12 0/8 (0.00%)  0 6/281 (2.14%)  8
Febrile neutropenia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  2 7/562 (1.25%)  7 0/8 (0.00%)  0 3/281 (1.07%)  3
Leukopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  6 0/8 (0.00%)  0 0/281 (0.00%)  0
Lymphopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Myelosuppression † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Neutropenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 5/562 (0.89%)  7 0/8 (0.00%)  0 4/281 (1.42%)  4
Pancytopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Thrombocytopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 11/562 (1.96%)  14 0/8 (0.00%)  0 4/281 (1.42%)  7
Thrombotic microangiopathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cardiac disorders             
Acute myocardial infarction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Arrhythmia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Atrial fibrillation † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cardiac arrest † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cardiac failure † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Cardiac failure congestive † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cardio-respiratory arrest † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Cardiopulmonary failure † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Myocarditis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Sinus bradycardia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Endocrine disorders             
Adrenal insufficiency † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  4 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypothyroidism † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Inappropriate antidiuretic hormone secretion † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Eye disorders             
Papilloedema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Cheilitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Colitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Diarrhoea † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  4 0/8 (0.00%)  0 0/281 (0.00%)  0
Dysphagia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Food poisoning † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Gastric ulcer haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Gastritis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Haematemesis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Intestinal obstruction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  2 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Intestinal pseudo-obstruction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Lower gastrointestinal haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Nausea † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 3/281 (1.07%)  3
Pancreatitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Stomatitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Vomiting † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 10/562 (1.78%)  12 0/8 (0.00%)  0 6/281 (2.14%)  7
General disorders             
Asthenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 2/281 (0.71%)  2
Chest pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Death † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Drug withdrawal syndrome † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Face oedema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Fat necrosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Fatigue † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Malaise † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 0/281 (0.00%)  0
Multiple organ dysfunction syndrome † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Non-cardiac chest pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Oedema peripheral † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pyrexia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 7/562 (1.25%)  8 0/8 (0.00%)  0 4/281 (1.42%)  6
Hepatobiliary disorders             
Autoimmune hepatitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hepatic function abnormal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Hepatitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  5 0/8 (0.00%)  0 0/281 (0.00%)  0
Hepatotoxicity † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Liver disorder † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Steatohepatitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Immune system disorders             
Anaphylactic reaction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Infections and infestations             
Abdominal abscess † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Abscess † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Bacteraemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Biliary tract infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Breast cellulitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Cellulitis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Cystitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Device related infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Device related sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Gastroenteritis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Herpes zoster † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Influenza † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Lower respiratory tract infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Mastitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 1/8 (12.50%)  1 0/281 (0.00%)  0
Meningitis aseptic † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Nasopharyngitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Neutropenic sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumocystis jirovecii pneumonia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumonia † 1  2/13 (15.38%)  2 0/10 (0.00%)  0 0/11 (0.00%)  0 11/562 (1.96%)  11 0/8 (0.00%)  0 7/281 (2.49%)  7
Pneumonia bacterial † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumonia mycoplasmal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Pneumonia staphylococcal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumonia streptococcal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pseudomonal sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Pulmonary sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pyelonephritis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Respiratory tract infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Sepsis † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 6/562 (1.07%)  6 0/8 (0.00%)  0 3/281 (1.07%)  3
Septic shock † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Skin infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Soft tissue infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 0/281 (0.00%)  0
Staphylococcal infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Staphylococcal sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Streptococcal sepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Superinfection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Upper respiratory tract infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Urinary tract infection † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Urosepsis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Vascular device infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 1/8 (12.50%)  1 1/281 (0.36%)  1
Viral infection † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Injury, poisoning and procedural complications             
Contusion † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Ligament sprain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Limb injury † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Lumbar vertebral fracture † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Procedural pneumothorax † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Radius fracture † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 2/281 (0.71%)  2
Rib fracture † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Transfusion reaction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Transfusion-related acute lung injury † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Traumatic intracranial haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Vascular access complication † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Investigations             
Alanine aminotransferase increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  5 0/8 (0.00%)  0 1/281 (0.36%)  1
Aspartate aminotransferase increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  5 0/8 (0.00%)  0 1/281 (0.36%)  1
Blood corticotrophin increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 1/8 (12.50%)  1 0/281 (0.00%)  0
Blood creatinine increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Cortisol decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Hepatic enzyme increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Liver function test abnormal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Neutrophil count decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pancreatic enzymes increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Platelet count decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 5/562 (0.89%)  6 0/8 (0.00%)  0 2/281 (0.71%)  2
Transaminases increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Dehydration † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Diabetes mellitus † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Diabetes mellitus inadequate control † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Electrolyte imbalance † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypercalcaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypoalbuminaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Hypocalcaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 2/281 (0.71%)  2
Hypokalaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hyponatraemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 2/281 (0.71%)  2
Type 1 diabetes mellitus † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Bone pain † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Musculoskeletal pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Myositis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pain in extremity † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pathological fracture † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Polyarthritis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Scleroderma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Adenocarcinoma of colon † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Basal cell carcinoma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cancer pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Chronic lymphocytic leukaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Endometrial adenocarcinoma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Tumour haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Tumour necrosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Tumour pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Nervous system disorders             
Brain oedema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cerebellar haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Cerebral haematoma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cerebral venous sinus thrombosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Cerebrovascular accident † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Chronic inflammatory demyelinating polyradiculoneuropathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Guillain-Barre syndrome † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Haemorrhagic stroke † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Headache † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 2/281 (0.71%)  2
Hepatic encephalopathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Intracranial pressure increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Myelopathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Parkinsonism † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Peripheral motor neuropathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Peripheral sensory neuropathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 2/281 (0.71%)  2
Syncope † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Transient ischaemic attack † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Product Issues             
Device dislocation † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Psychiatric disorders             
Anxiety † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Assisted suicide † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Confusional state † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Renal and urinary disorders             
Acute kidney injury † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 1/281 (0.36%)  2
Hydronephrosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Kidney enlargement † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Nephritis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Renal failure † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Urinary retention † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Urinary tract obstruction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Reproductive system and breast disorders             
Abnormal uterine bleeding † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Breast pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Uterine haemorrhage † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Respiratory, thoracic and mediastinal disorders             
Asthma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Bronchostenosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Chronic obstructive pulmonary disease † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Dyspnoea † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Obstructive airways disorder † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Pleural effusion † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 5/562 (0.89%)  6 0/8 (0.00%)  0 3/281 (1.07%)  3
Pleurisy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pleuritic pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumonia aspiration † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumonitis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 6/562 (1.07%)  8 0/8 (0.00%)  0 0/281 (0.00%)  0
Pneumothorax † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 2/281 (0.71%)  2
Pulmonary embolism † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 7/562 (1.25%)  7 0/8 (0.00%)  0 3/281 (1.07%)  3
Pulmonary fibrosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Pulmonary hypertension † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Respiratory failure † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Skin and subcutaneous tissue disorders             
Drug eruption † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Rash maculo-papular † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Subcutaneous emphysema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Vascular disorders             
Deep vein thrombosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Embolism † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypertension † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypertensive emergency † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypotension † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Shock haemorrhagic † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Thrombosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Varicose vein † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Venous thrombosis limb † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Pembrolizumab + Nab-paclitaxel Part 1: Pembrolizumab + Paclitaxel Part 1: Pembrolizumab + Gemcitabine/Carboplatin Part 2: Pembrolizumab + Chemotherapy (First Course) Part 2: Pembrolizumab + Chemotherapy (Second Course) Part 2: Placebo + Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/13 (100.00%)      10/10 (100.00%)      11/11 (100.00%)      551/562 (98.04%)      7/8 (87.50%)      273/281 (97.15%)    
Blood and lymphatic system disorders             
Anaemia † 1  5/13 (38.46%)  5 5/10 (50.00%)  15 8/11 (72.73%)  13 294/562 (52.31%)  625 1/8 (12.50%)  3 140/281 (49.82%)  246
Leukopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 2/11 (18.18%)  44 111/562 (19.75%)  447 0/8 (0.00%)  0 50/281 (17.79%)  158
Lymphopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 30/562 (5.34%)  62 0/8 (0.00%)  0 4/281 (1.42%)  15
Neutropenia † 1  2/13 (15.38%)  3 1/10 (10.00%)  21 7/11 (63.64%)  67 232/562 (41.28%)  928 1/8 (12.50%)  1 109/281 (38.79%)  377
Thrombocytopenia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 5/11 (45.45%)  63 110/562 (19.57%)  346 0/8 (0.00%)  0 56/281 (19.93%)  155
Cardiac disorders             
Tachycardia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 8/562 (1.42%)  11 0/8 (0.00%)  0 3/281 (1.07%)  3
Ear and labyrinth disorders             
Vertigo † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 20/562 (3.56%)  22 0/8 (0.00%)  0 12/281 (4.27%)  13
Endocrine disorders             
Adrenal insufficiency † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  4 0/8 (0.00%)  0 0/281 (0.00%)  0
Hyperthyroidism † 1  1/13 (7.69%)  1 2/10 (20.00%)  3 1/11 (9.09%)  1 24/562 (4.27%)  24 0/8 (0.00%)  0 3/281 (1.07%)  3
Hypophysitis † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypothyroidism † 1  1/13 (7.69%)  1 3/10 (30.00%)  3 4/11 (36.36%)  5 88/562 (15.66%)  100 0/8 (0.00%)  0 9/281 (3.20%)  10
Thyroiditis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 6/562 (1.07%)  6 0/8 (0.00%)  0 0/281 (0.00%)  0
Eye disorders             
Diplopia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 5/281 (1.78%)  5
Dry eye † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 20/562 (3.56%)  20 0/8 (0.00%)  0 8/281 (2.85%)  8
Eye pain † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 0/281 (0.00%)  0
Eye pruritus † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 3/562 (0.53%)  3 0/8 (0.00%)  0 5/281 (1.78%)  5
Eye swelling † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Eyelid cyst † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Ocular discomfort † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Vision blurred † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 9/562 (1.60%)  11 0/8 (0.00%)  0 8/281 (2.85%)  8
Gastrointestinal disorders             
Abdominal discomfort † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 6/281 (2.14%)  6
Abdominal distension † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 11/562 (1.96%)  13 0/8 (0.00%)  0 6/281 (2.14%)  7
Abdominal pain † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 3/11 (27.27%)  6 43/562 (7.65%)  57 0/8 (0.00%)  0 25/281 (8.90%)  27
Abdominal pain upper † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 1/11 (9.09%)  1 44/562 (7.83%)  62 1/8 (12.50%)  1 16/281 (5.69%)  19
Anal fissure † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 4/562 (0.71%)  4 0/8 (0.00%)  0 2/281 (0.71%)  3
Colitis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 8/562 (1.42%)  9 0/8 (0.00%)  0 3/281 (1.07%)  3
Constipation † 1  3/13 (23.08%)  3 3/10 (30.00%)  3 6/11 (54.55%)  10 155/562 (27.58%)  211 0/8 (0.00%)  0 77/281 (27.40%)  97
Dental caries † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 6/562 (1.07%)  6 0/8 (0.00%)  0 2/281 (0.71%)  2
Diarrhoea † 1  5/13 (38.46%)  9 2/10 (20.00%)  3 6/11 (54.55%)  6 155/562 (27.58%)  305 1/8 (12.50%)  2 66/281 (23.49%)  129
Dry mouth † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 22/562 (3.91%)  23 0/8 (0.00%)  0 10/281 (3.56%)  14
Dyspepsia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 38/562 (6.76%)  45 0/8 (0.00%)  0 16/281 (5.69%)  19
Flatulence † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 11/562 (1.96%)  13 0/8 (0.00%)  0 1/281 (0.36%)  1
Gastritis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 18/562 (3.20%)  18 1/8 (12.50%)  1 7/281 (2.49%)  7
Gastrooesophageal reflux disease † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 15/562 (2.67%)  16 0/8 (0.00%)  0 11/281 (3.91%)  12
Gingival bleeding † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 1/8 (12.50%)  1 0/281 (0.00%)  0
Large intestinal haemorrhage † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Nausea † 1  6/13 (46.15%)  7 2/10 (20.00%)  3 4/11 (36.36%)  9 251/562 (44.66%)  523 0/8 (0.00%)  0 130/281 (46.26%)  252
Stomatitis † 1  0/13 (0.00%)  0 2/10 (20.00%)  2 0/11 (0.00%)  0 54/562 (9.61%)  76 0/8 (0.00%)  0 19/281 (6.76%)  22
Vomiting † 1  3/13 (23.08%)  5 2/10 (20.00%)  2 6/11 (54.55%)  8 140/562 (24.91%)  245 0/8 (0.00%)  0 61/281 (21.71%)  105
General disorders             
Asthenia † 1  6/13 (46.15%)  16 3/10 (30.00%)  8 3/11 (27.27%)  6 107/562 (19.04%)  193 0/8 (0.00%)  0 47/281 (16.73%)  84
Chest pain † 1  2/13 (15.38%)  2 1/10 (10.00%)  1 0/11 (0.00%)  0 25/562 (4.45%)  27 0/8 (0.00%)  0 17/281 (6.05%)  20
Chills † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 16/562 (2.85%)  18 1/8 (12.50%)  1 6/281 (2.14%)  6
Fatigue † 1  1/13 (7.69%)  1 2/10 (20.00%)  3 1/11 (9.09%)  1 180/562 (32.03%)  257 0/8 (0.00%)  0 96/281 (34.16%)  118
Infusion site extravasation † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 3/562 (0.53%)  3 0/8 (0.00%)  0 0/281 (0.00%)  0
Infusion site pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Injection site reaction † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Malaise † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 25/562 (4.45%)  38 0/8 (0.00%)  0 14/281 (4.98%)  25
Mucosal dryness † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Mucosal inflammation † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 31/562 (5.52%)  41 0/8 (0.00%)  0 14/281 (4.98%)  21
Oedema † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Oedema peripheral † 1  5/13 (38.46%)  5 0/10 (0.00%)  0 0/11 (0.00%)  0 65/562 (11.57%)  84 0/8 (0.00%)  0 29/281 (10.32%)  42
Pyrexia † 1  3/13 (23.08%)  3 2/10 (20.00%)  2 2/11 (18.18%)  4 98/562 (17.44%)  149 1/8 (12.50%)  2 55/281 (19.57%)  86
Thirst † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  2
Hepatobiliary disorders             
Hepatic function abnormal † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 5/562 (0.89%)  6 1/8 (12.50%)  1 3/281 (1.07%)  3
Immune system disorders             
Contrast media allergy † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 1/8 (12.50%)  1 0/281 (0.00%)  0
Hypersensitivity † 1  0/13 (0.00%)  0 2/10 (20.00%)  3 0/11 (0.00%)  0 8/562 (1.42%)  9 0/8 (0.00%)  0 8/281 (2.85%)  16
Infections and infestations             
Cellulitis † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 8/562 (1.42%)  8 0/8 (0.00%)  0 4/281 (1.42%)  5
Conjunctivitis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  1 7/562 (1.25%)  9 0/8 (0.00%)  0 3/281 (1.07%)  13
Conjunctivitis viral † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Cystitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 2/11 (18.18%)  2 11/562 (1.96%)  13 0/8 (0.00%)  0 3/281 (1.07%)  5
Erythema infectiosum † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Gastroenteritis † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 8/562 (1.42%)  9 0/8 (0.00%)  0 5/281 (1.78%)  6
Gastrointestinal infection † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Hordeolum † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 2/281 (0.71%)  2
Influenza † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  2 28/562 (4.98%)  30 0/8 (0.00%)  0 7/281 (2.49%)  9
Nasopharyngitis † 1  3/13 (23.08%)  3 0/10 (0.00%)  0 1/11 (9.09%)  1 52/562 (9.25%)  75 1/8 (12.50%)  1 21/281 (7.47%)  27
Oral candidiasis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  1 7/562 (1.25%)  7 0/8 (0.00%)  0 4/281 (1.42%)  6
Oropharyngeal candidiasis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Pharyngitis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 8/562 (1.42%)  8 0/8 (0.00%)  0 5/281 (1.78%)  8
Rash pustular † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  4 0/8 (0.00%)  0 1/281 (0.36%)  1
Rhinitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 5/562 (0.89%)  5 0/8 (0.00%)  0 6/281 (2.14%)  8
Skin infection † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 6/562 (1.07%)  7 0/8 (0.00%)  0 4/281 (1.42%)  4
Tonsillitis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 8/562 (1.42%)  9 0/8 (0.00%)  0 1/281 (0.36%)  1
Upper respiratory tract infection † 1  5/13 (38.46%)  5 3/10 (30.00%)  4 1/11 (9.09%)  8 58/562 (10.32%)  94 0/8 (0.00%)  0 25/281 (8.90%)  34
Urinary tract infection † 1  1/13 (7.69%)  2 1/10 (10.00%)  1 1/11 (9.09%)  1 48/562 (8.54%)  68 1/8 (12.50%)  1 13/281 (4.63%)  14
Viral diarrhoea † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Viral infection † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 8/562 (1.42%)  11 0/8 (0.00%)  0 4/281 (1.42%)  6
Viral upper respiratory tract infection † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  5 0/8 (0.00%)  0 2/281 (0.71%)  2
Injury, poisoning and procedural complications             
Contusion † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 9/562 (1.60%)  10 0/8 (0.00%)  0 3/281 (1.07%)  3
Incision site pain † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Limb injury † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Thermal burn † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  2 4/562 (0.71%)  4 0/8 (0.00%)  0 0/281 (0.00%)  0
Wound complication † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Investigations             
Alanine aminotransferase increased † 1  1/13 (7.69%)  1 1/10 (10.00%)  2 2/11 (18.18%)  28 139/562 (24.73%)  242 1/8 (12.50%)  1 54/281 (19.22%)  81
Amylase increased † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Aspartate aminotransferase increased † 1  1/13 (7.69%)  1 1/10 (10.00%)  2 2/11 (18.18%)  17 131/562 (23.31%)  224 0/8 (0.00%)  0 46/281 (16.37%)  69
Blood alkaline phosphatase increased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 50/562 (8.90%)  79 1/8 (12.50%)  1 22/281 (7.83%)  26
Blood cholesterol increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  3 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Blood corticotrophin increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 1/8 (12.50%)  1 0/281 (0.00%)  0
Blood iron decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Blood lactate dehydrogenase increased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 31/562 (5.52%)  34 0/8 (0.00%)  0 16/281 (5.69%)  17
Blood thyroid stimulating hormone increased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 11/562 (1.96%)  11 0/8 (0.00%)  0 3/281 (1.07%)  3
Cortisol decreased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 1/281 (0.36%)  1
Gamma-glutamyltransferase increased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 2/11 (18.18%)  2 20/562 (3.56%)  35 0/8 (0.00%)  0 8/281 (2.85%)  11
Haemoglobin decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  3 14/562 (2.49%)  20 0/8 (0.00%)  0 3/281 (1.07%)  4
Lipase increased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Lymphocyte count decreased † 1  0/13 (0.00%)  0 3/10 (30.00%)  7 1/11 (9.09%)  1 30/562 (5.34%)  88 2/8 (25.00%)  5 11/281 (3.91%)  32
Lymphocyte percentage decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  36 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Neutrophil count decreased † 1  2/13 (15.38%)  2 5/10 (50.00%)  17 1/11 (9.09%)  1 128/562 (22.78%)  665 2/8 (25.00%)  9 75/281 (26.69%)  311
Neutrophil percentage decreased † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 6/562 (1.07%)  24 0/8 (0.00%)  0 1/281 (0.36%)  9
Platelet count decreased † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 87/562 (15.48%)  346 1/8 (12.50%)  6 44/281 (15.66%)  125
Transaminases increased † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  4 0/8 (0.00%)  0 4/281 (1.42%)  4
Weight decreased † 1  1/13 (7.69%)  2 4/10 (40.00%)  5 1/11 (9.09%)  1 50/562 (8.90%)  55 0/8 (0.00%)  0 12/281 (4.27%)  13
Weight increased † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  2 14/562 (2.49%)  14 0/8 (0.00%)  0 7/281 (2.49%)  8
White blood cell count decreased † 1  0/13 (0.00%)  0 5/10 (50.00%)  20 2/11 (18.18%)  3 106/562 (18.86%)  497 2/8 (25.00%)  8 54/281 (19.22%)  210
Metabolism and nutrition disorders             
Decreased appetite † 1  8/13 (61.54%)  12 2/10 (20.00%)  2 2/11 (18.18%)  4 118/562 (21.00%)  140 0/8 (0.00%)  0 39/281 (13.88%)  49
Hyperglycaemia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  4 27/562 (4.80%)  40 0/8 (0.00%)  0 11/281 (3.91%)  11
Hyperuricaemia † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  37 9/562 (1.60%)  13 0/8 (0.00%)  0 8/281 (2.85%)  9
Hypoalbuminaemia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 2/11 (18.18%)  28 19/562 (3.38%)  30 0/8 (0.00%)  0 11/281 (3.91%)  11
Hypoglycaemia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  3 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Hypokalaemia † 1  0/13 (0.00%)  0 1/10 (10.00%)  4 1/11 (9.09%)  2 28/562 (4.98%)  47 0/8 (0.00%)  0 14/281 (4.98%)  19
Hyponatraemia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 12/562 (2.14%)  14 0/8 (0.00%)  0 6/281 (2.14%)  6
Musculoskeletal and connective tissue disorders             
Arthralgia † 1  3/13 (23.08%)  3 1/10 (10.00%)  1 2/11 (18.18%)  2 120/562 (21.35%)  197 0/8 (0.00%)  0 50/281 (17.79%)  74
Arthritis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 6/562 (1.07%)  8 0/8 (0.00%)  0 2/281 (0.71%)  2
Back pain † 1  2/13 (15.38%)  2 0/10 (0.00%)  0 0/11 (0.00%)  0 73/562 (12.99%)  90 1/8 (12.50%)  2 42/281 (14.95%)  49
Bone pain † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 22/562 (3.91%)  25 0/8 (0.00%)  0 17/281 (6.05%)  21
Coccydynia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Groin pain † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 5/562 (0.89%)  6 0/8 (0.00%)  0 1/281 (0.36%)  1
Joint swelling † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 2/11 (18.18%)  2 2/562 (0.36%)  3 0/8 (0.00%)  0 1/281 (0.36%)  1
Musculoskeletal chest pain † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 28/562 (4.98%)  31 0/8 (0.00%)  0 13/281 (4.63%)  16
Musculoskeletal pain † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 7/562 (1.25%)  12 0/8 (0.00%)  0 3/281 (1.07%)  4
Musculoskeletal stiffness † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 1/281 (0.36%)  1
Myalgia † 1  0/13 (0.00%)  0 3/10 (30.00%)  3 2/11 (18.18%)  3 58/562 (10.32%)  82 0/8 (0.00%)  0 34/281 (12.10%)  57
Neck pain † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  1 25/562 (4.45%)  28 0/8 (0.00%)  0 20/281 (7.12%)  24
Osteoporosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Pain in extremity † 1  3/13 (23.08%)  3 0/10 (0.00%)  0 0/11 (0.00%)  0 56/562 (9.96%)  67 0/8 (0.00%)  0 41/281 (14.59%)  46
Pain in jaw † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 10/562 (1.78%)  11 0/8 (0.00%)  0 2/281 (0.71%)  2
Spinal pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 2/11 (18.18%)  2 5/562 (0.89%)  5 0/8 (0.00%)  0 2/281 (0.71%)  2
Nervous system disorders             
Ataxia † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Dementia Alzheimer's type † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Dizziness † 1  1/13 (7.69%)  1 3/10 (30.00%)  4 0/11 (0.00%)  0 52/562 (9.25%)  60 0/8 (0.00%)  0 24/281 (8.54%)  33
Dysgeusia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 54/562 (9.61%)  63 0/8 (0.00%)  0 15/281 (5.34%)  18
Headache † 1  2/13 (15.38%)  3 5/10 (50.00%)  7 1/11 (9.09%)  1 111/562 (19.75%)  184 0/8 (0.00%)  0 65/281 (23.13%)  102
Lethargy † 1  1/13 (7.69%)  2 0/10 (0.00%)  0 1/11 (9.09%)  1 11/562 (1.96%)  15 0/8 (0.00%)  0 3/281 (1.07%)  5
Mental impairment † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Neuropathy peripheral † 1  4/13 (30.77%)  6 2/10 (20.00%)  2 1/11 (9.09%)  1 62/562 (11.03%)  72 0/8 (0.00%)  0 35/281 (12.46%)  50
Neurotoxicity † 1  2/13 (15.38%)  3 1/10 (10.00%)  2 0/11 (0.00%)  0 4/562 (0.71%)  7 0/8 (0.00%)  0 4/281 (1.42%)  7
Paraesthesia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 24/562 (4.27%)  31 0/8 (0.00%)  0 15/281 (5.34%)  15
Peripheral motor neuropathy † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 2/281 (0.71%)  2
Peripheral sensory neuropathy † 1  1/13 (7.69%)  1 3/10 (30.00%)  4 2/11 (18.18%)  2 49/562 (8.72%)  55 0/8 (0.00%)  0 20/281 (7.12%)  22
Polyneuropathy † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 12/562 (2.14%)  12 0/8 (0.00%)  0 0/281 (0.00%)  0
Presyncope † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  6 0/8 (0.00%)  0 4/281 (1.42%)  5
Somnolence † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 9/562 (1.60%)  9 0/8 (0.00%)  0 6/281 (2.14%)  8
Taste disorder † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 8/562 (1.42%)  9 0/8 (0.00%)  0 5/281 (1.78%)  5
Psychiatric disorders             
Anxiety † 1  0/13 (0.00%)  0 2/10 (20.00%)  2 3/11 (27.27%)  4 22/562 (3.91%)  22 0/8 (0.00%)  0 11/281 (3.91%)  11
Depressed mood † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 3/562 (0.53%)  4 0/8 (0.00%)  0 2/281 (0.71%)  4
Depression † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 20/562 (3.56%)  20 0/8 (0.00%)  0 13/281 (4.63%)  13
Insomnia † 1  1/13 (7.69%)  2 2/10 (20.00%)  2 2/11 (18.18%)  2 47/562 (8.36%)  52 0/8 (0.00%)  0 27/281 (9.61%)  31
Persistent depressive disorder † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Stress † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Renal and urinary disorders             
Dysuria † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 12/562 (2.14%)  12 0/8 (0.00%)  0 3/281 (1.07%)  3
Polyuria † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Reproductive system and breast disorders             
Breast pain † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1 24/562 (4.27%)  29 0/8 (0.00%)  0 14/281 (4.98%)  14
Respiratory, thoracic and mediastinal disorders             
Asthma † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 1/281 (0.36%)  1
Bronchostenosis † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Cough † 1  2/13 (15.38%)  2 4/10 (40.00%)  4 2/11 (18.18%)  2 117/562 (20.82%)  153 0/8 (0.00%)  0 49/281 (17.44%)  58
Dyspnoea † 1  1/13 (7.69%)  1 2/10 (20.00%)  3 1/11 (9.09%)  1 69/562 (12.28%)  82 0/8 (0.00%)  0 37/281 (13.17%)  43
Dyspnoea exertional † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 5/562 (0.89%)  5 0/8 (0.00%)  0 5/281 (1.78%)  6
Epistaxis † 1  0/13 (0.00%)  0 2/10 (20.00%)  3 0/11 (0.00%)  0 20/562 (3.56%)  26 0/8 (0.00%)  0 17/281 (6.05%)  20
Haemoptysis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 2/281 (0.71%)  2
Nasal dryness † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 1/562 (0.18%)  1 1/8 (12.50%)  1 1/281 (0.36%)  1
Nasal pruritus † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 1/8 (12.50%)  1 0/281 (0.00%)  0
Oropharyngeal pain † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0 29/562 (5.16%)  32 0/8 (0.00%)  0 18/281 (6.41%)  25
Pneumothorax † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 3/281 (1.07%)  3
Productive cough † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 12/562 (2.14%)  12 0/8 (0.00%)  0 13/281 (4.63%)  15
Pulmonary embolism † 1  1/13 (7.69%)  2 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 4/281 (1.42%)  4
Sinus congestion † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Throat irritation † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Skin and subcutaneous tissue disorders             
Alopecia † 1  4/13 (30.77%)  4 5/10 (50.00%)  5 2/11 (18.18%)  2 190/562 (33.81%)  196 0/8 (0.00%)  0 97/281 (34.52%)  97
Butterfly rash † 1  1/13 (7.69%)  2 0/10 (0.00%)  0 0/11 (0.00%)  0 0/562 (0.00%)  0 0/8 (0.00%)  0 0/281 (0.00%)  0
Dermatitis acneiform † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  3 11/562 (1.96%)  11 0/8 (0.00%)  0 6/281 (2.14%)  7
Dermatitis contact † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 7/562 (1.25%)  8 0/8 (0.00%)  0 4/281 (1.42%)  4
Drug eruption † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Dry skin † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 1/11 (9.09%)  1 16/562 (2.85%)  18 0/8 (0.00%)  0 10/281 (3.56%)  10
Dyshidrotic eczema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 2/562 (0.36%)  2 0/8 (0.00%)  0 0/281 (0.00%)  0
Erythema † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 23/562 (4.09%)  25 0/8 (0.00%)  0 11/281 (3.91%)  18
Erythema nodosum † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Hyperhidrosis † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 7/562 (1.25%)  7 0/8 (0.00%)  0 4/281 (1.42%)  4
Nail discolouration † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 7/562 (1.25%)  7 0/8 (0.00%)  0 10/281 (3.56%)  10
Nail dystrophy † 1  1/13 (7.69%)  1 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 1/281 (0.36%)  1
Onychalgia † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 3/281 (1.07%)  4
Palmar-plantar erythrodysaesthesia syndrome † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 3/562 (0.53%)  3 0/8 (0.00%)  0 2/281 (0.71%)  2
Pruritus † 1  3/13 (23.08%)  3 3/10 (30.00%)  6 1/11 (9.09%)  1 85/562 (15.12%)  119 1/8 (12.50%)  1 32/281 (11.39%)  39
Rash † 1  2/13 (15.38%)  2 2/10 (20.00%)  4 3/11 (27.27%)  4 110/562 (19.57%)  154 0/8 (0.00%)  0 34/281 (12.10%)  44
Rash maculo-papular † 1  0/13 (0.00%)  0 3/10 (30.00%)  3 0/11 (0.00%)  0 25/562 (4.45%)  41 0/8 (0.00%)  0 10/281 (3.56%)  10
Rash papular † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 3/562 (0.53%)  4 0/8 (0.00%)  0 0/281 (0.00%)  0
Rash pruritic † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 6/562 (1.07%)  7 0/8 (0.00%)  0 2/281 (0.71%)  2
Skin hyperpigmentation † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 7/562 (1.25%)  7 0/8 (0.00%)  0 1/281 (0.36%)  1
Skin lesion † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 4/562 (0.71%)  5 1/8 (12.50%)  1 4/281 (1.42%)  4
Skin mass † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 1/562 (0.18%)  1 0/8 (0.00%)  0 0/281 (0.00%)  0
Urticaria † 1  0/13 (0.00%)  0 1/10 (10.00%)  2 1/11 (9.09%)  1 11/562 (1.96%)  15 0/8 (0.00%)  0 3/281 (1.07%)  4
Vascular disorders             
Flushing † 1  0/13 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0 11/562 (1.96%)  22 0/8 (0.00%)  0 3/281 (1.07%)  3
Haematoma † 1  1/13 (7.69%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0 5/562 (0.89%)  6 0/8 (0.00%)  0 2/281 (0.71%)  2
Hot flush † 1  1/13 (7.69%)  1 1/10 (10.00%)  2 0/11 (0.00%)  0 21/562 (3.74%)  22 0/8 (0.00%)  0 10/281 (3.56%)  14
Hypotension † 1  3/13 (23.08%)  3 0/10 (0.00%)  0 0/11 (0.00%)  0 11/562 (1.96%)  11 0/8 (0.00%)  0 9/281 (3.20%)  10
Lymphoedema † 1  0/13 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1 16/562 (2.85%)  17 0/8 (0.00%)  0 11/281 (3.91%)  11
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT02819518    
Other Study ID Numbers: 3475-355
163422 ( Registry Identifier: JAPAN-CTI )
MK-3475-355 ( Other Identifier: Merck )
KEYNOTE-355 ( Other Identifier: Merck )
2016-001432-35 ( EudraCT Number )
First Submitted: June 28, 2016
First Posted: June 30, 2016
Results First Submitted: June 8, 2022
Results First Posted: July 5, 2022
Last Update Posted: November 9, 2023