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Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)-Japan Extension Study

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ClinicalTrials.gov Identifier: NCT03950674
Recruitment Status : Completed
First Posted : May 15, 2019
Results First Posted : June 11, 2020
Last Update Posted : July 20, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Non-Small-Cell Lung Carcinoma
Interventions Biological: Pembrolizumab 200 mg
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Dietary Supplement: Folic acid 350-1000 μg
Dietary Supplement: Vitamin B12 1000 μg
Drug: Dexamethasone 4 mg
Drug: Saline solution
Enrollment 40
Recruitment Details The MK-3475-189-Japanese Extension Study enrolled a total of 30 participants and the analyses included 10 participants (pembrolizumab =4; control = 6) that had been previously enrolled in the MK-3475-189 global study (NCT02578680), resulting in a total of 40 participants.
Pre-assignment Details These results are based on a database cutoff date of 20-May-2019, at which time 30 participants were ongoing in the study. Four participants randomized to receive Control treatment had switched over to receive pembrolizumab monotherapy treatment. These results are for randomized treatment only.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Period Title: Overall Study
Started 25 15
Treated 25 15
Switched to Pembrolizumab 0 4
Completed 0 0
Not Completed 25 15
Reason Not Completed
Death             3             7
Ongoing in Study             22             8
Arm/Group Title Pembrolizumab Control Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression. Total of all reporting groups
Overall Number of Baseline Participants 25 15 40
Hide Baseline Analysis Population Description
The Baseline Analysis Population consisted of all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 15 participants 40 participants
59.6  (12.7) 60.9  (11.8) 60.1  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
Female
6
  24.0%
3
  20.0%
9
  22.5%
Male
19
  76.0%
12
  80.0%
31
  77.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
25
 100.0%
15
 100.0%
40
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
25
 100.0%
15
 100.0%
40
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 25 participants 15 participants 40 participants
TPS <1%
14
  56.0%
6
  40.0%
20
  50.0%
TPS ≥1%
10
  40.0%
6
  40.0%
16
  40.0%
Not Evaluable
1
   4.0%
3
  20.0%
4
  10.0%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a TPS ≥1% were classified as PD-L1 positive and participants with a TPS <1% were classified as PD-L1 negative.
Platinum Chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 25 participants 15 participants 40 participants
Cisplatin
18
  72.0%
8
  53.3%
26
  65.0%
Carboplatin
7
  28.0%
7
  46.7%
14
  35.0%
[1]
Measure Description: Participants were classified according to the type of platinum chemotherapy the Investigator chose for them to receive: Cisplatin or Carboplatin.
Smoking Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 25 participants 15 participants 40 participants
Never Smoker
7
  28.0%
3
  20.0%
10
  25.0%
Former/Current Smoker
18
  72.0%
12
  80.0%
30
  75.0%
[1]
Measure Description: Participants were classified according to their smoking status: Never Smoker or Former/Current Smoker.
1.Primary Outcome
Title Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented.
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Median (95% Confidence Interval)
Unit of Measure: Months
16.5
(8.8 to 21.1)
7.1
(4.7 to 21.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12511
Comments One-sided p-value based on unstratified log-rank test
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.27 to 1.42
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by PD-L1 status (≥1% vs. <1%), platinum chemotherapy (cisplatin vs. carboplatin) & smoking status (never vs. former/current). Pembrolizumab=numerator; Control=denominator.
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS is presented.
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
25.9
(11.9 to 29.0)
[1]
NA=Median OS not reached NA=Lower Limit OS not reached NA=Upper Limit OS not reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03127
Comments One-sided p-value based on unstratified log-rank test
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.07 to 1.15
Estimation Comments Based on Cox regression model with treatment as a covariate stratified by PD-L1 status (≥1% vs. <1%), platinum chemotherapy (cisplatin vs. carboplatin) & smoking status (never vs. former/current). Pembrolizumab=numerator; Control=denominator.
3.Secondary Outcome
Title Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
Hide Description ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented.
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
56.0
(34.9 to 75.6)
33.3
(11.8 to 61.6)
4.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.
Time Frame From time of first documented evidence of CR or PR through database cutoff date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who experienced a confirmed CR or confirmed PR.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 14 5
Median (95% Confidence Interval)
Unit of Measure: Months
13.6
(5.9 to 19.6)
9.7 [1] 
(3.4 to NA)
[1]
NA=Upper Limit DOR not reached
5.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug. The number of participants who experienced an AE is presented.
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received ≥1 dose of study drug.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Measure Type: Count of Participants
Unit of Measure: Participants
25
 100.0%
15
 100.0%
6.Secondary Outcome
Title Number of Participants Who Discontinued Any Study Drug Due to an AE
Hide Description The number of participants who discontinued any randomized study drug due to an AE is presented.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants who received ≥1 dose of study drug.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Measure Type: Count of Participants
Unit of Measure: Participants
9
  36.0%
3
  20.0%
7.Other Pre-specified Outcome
Title Progression-Free Survival (PFS) as Assessed by Investigator Immune-related RECIST (irRECIST) Response Criteria
Hide Description PFS was defined as the time from randomization to the first documented immune-related progressive disease (irPD) or death due to any cause, whichever occurred first. Per irRECIST, irPD was confirmed if any of the following are observed in 2 scans performed at least 4 weeks apart: target lesion sum of diameters remains ≥20 % and at least 5 mm absolute increase compared to nadir; non-target disease resulting in initial PD is qualitatively worse; new lesion resulting in initial irPD is qualitatively worse; additional new lesion(s) since last evaluation; or additional new non-target lesion progression since last evaluation. The PFS per irRECIST 1.1 is presented.
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all randomized participants.
Arm/Group Title Pembrolizumab Control
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.
Overall Number of Participants Analyzed 25 15
Median (95% Confidence Interval)
Unit of Measure: Months
13.7
(6.4 to 22.0)
7.6
(2.6 to 11.9)
Time Frame Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months); Serious AEs: Up to 90 days after last dose of study drug, Other AEs: Up to 30 days after last dose of study drug
Adverse Event Reporting Description Population: All participants receiving ≥1 dose of randomized study drug. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs. Four participants randomized to receive control and switched to pembrolizumab were continued to be monitored for AEs.
 
Arm/Group Title Pembrolizumab Control Placebo Switched to Pembrolizumab Monotherapy
Hide Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression. Participants originally randomized to the placebo arm that experienced disease progression were given pembrolizumab 200 mg IV on Day 1 Q3W after the study was unblinded.
All-Cause Mortality
Pembrolizumab Control Placebo Switched to Pembrolizumab Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/25 (12.00%)      7/15 (46.67%)      2/4 (50.00%)    
Hide Serious Adverse Events
Pembrolizumab Control Placebo Switched to Pembrolizumab Monotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/25 (36.00%)      6/15 (40.00%)      1/4 (25.00%)    
Endocrine disorders       
Adrenal insufficiency † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
General disorders       
Pyrexia † 1  2/25 (8.00%)  4 0/15 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders       
Hepatic function abnormal † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations       
Bacterial infection † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Oesophageal infection † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Parotitis † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications       
Radiation oesophagitis † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Myalgia † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumour necrosis † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Nervous system disorders       
Brain oedema † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Cerebral haemorrhage † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Polyneuropathy † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Interstitial lung disease † 1  0/25 (0.00%)  0 2/15 (13.33%)  2 0/4 (0.00%)  0
Pneumonitis † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 1/4 (25.00%)  1
Skin and subcutaneous tissue disorders       
Toxic epidermal necrolysis † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders       
Deep vein thrombosis † 1  1/25 (4.00%)  1 0/15 (0.00%)  0 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab Control Placebo Switched to Pembrolizumab Monotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/25 (100.00%)      15/15 (100.00%)      4/4 (100.00%)    
Blood and lymphatic system disorders       
Anaemia † 1  11/25 (44.00%)  17 10/15 (66.67%)  11 0/4 (0.00%)  0
Leukopenia † 1  0/25 (0.00%)  0 7/15 (46.67%)  13 0/4 (0.00%)  0
Neutropenia † 1  3/25 (12.00%)  5 3/15 (20.00%)  8 0/4 (0.00%)  0
Thrombocytopenia † 1  1/25 (4.00%)  1 4/15 (26.67%)  5 0/4 (0.00%)  0
Lymphopenia † 1  0/25 (0.00%)  0 2/15 (13.33%)  3 0/4 (0.00%)  0
Ear and labyrinth disorders       
Hypoacusis † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Tinnitus † 1  3/25 (12.00%)  3 1/15 (6.67%)  2 0/4 (0.00%)  0
Endocrine disorders       
Hypothyroidism † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Hyperthyroidism † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Eye disorders       
Lacrimation increased † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Conjunctivitis allergic † 1  0/25 (0.00%)  0 1/15 (6.67%)  2 0/4 (0.00%)  0
Dry eye † 1  2/25 (8.00%)  3 0/15 (0.00%)  0 0/4 (0.00%)  0
Periorbital oedema † 1  3/25 (12.00%)  3 0/15 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders       
Constipation † 1  16/25 (64.00%)  22 11/15 (73.33%)  18 0/4 (0.00%)  0
Diarrhoea † 1  8/25 (32.00%)  9 2/15 (13.33%)  3 1/4 (25.00%)  1
Dry mouth † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Nausea † 1  18/25 (72.00%)  41 8/15 (53.33%)  19 1/4 (25.00%)  1
Stomatitis † 1  7/25 (28.00%)  9 4/15 (26.67%)  7 0/4 (0.00%)  0
Vomiting † 1  2/25 (8.00%)  4 4/15 (26.67%)  6 0/4 (0.00%)  0
Bowel movement irregularity † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Dental caries † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Large intestine polyp † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Oral hyperaesthesia † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
General disorders       
Face oedema † 1  5/25 (20.00%)  6 1/15 (6.67%)  1 0/4 (0.00%)  0
Fatigue † 1  4/25 (16.00%)  4 5/15 (33.33%)  7 0/4 (0.00%)  0
Infusion site extravasation † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Localised oedema † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Malaise † 1  5/25 (20.00%)  8 4/15 (26.67%)  6 0/4 (0.00%)  0
Oedema peripheral † 1  2/25 (8.00%)  2 5/15 (33.33%)  6 0/4 (0.00%)  0
Puncture site pain † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Pyrexia † 1  3/25 (12.00%)  7 1/15 (6.67%)  1 1/4 (25.00%)  1
Hepatobiliary disorders       
Hepatic function abnormal † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations       
Conjunctivitis † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Nasopharyngitis † 1  5/25 (20.00%)  11 1/15 (6.67%)  1 0/4 (0.00%)  0
Upper respiratory tract infection † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Enterocolitis infectious † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Herpes zoster † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Influenza † 1  2/25 (8.00%)  2 1/15 (6.67%)  1 0/4 (0.00%)  0
Oral candidiasis † 1  2/25 (8.00%)  3 0/15 (0.00%)  0 0/4 (0.00%)  0
Pharyngitis † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Lymph gland infection † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Joint dislocation † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Wound † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Investigations       
Alanine aminotransferase increased † 1  9/25 (36.00%)  14 5/15 (33.33%)  6 0/4 (0.00%)  0
Aspartate aminotransferase increased † 1  8/25 (32.00%)  11 5/15 (33.33%)  6 0/4 (0.00%)  0
Blood creatinine increased † 1  2/25 (8.00%)  4 1/15 (6.67%)  1 0/4 (0.00%)  0
Weight increased † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
White blood cell count decreased † 1  10/25 (40.00%)  20 3/15 (20.00%)  4 0/4 (0.00%)  0
Blood bilirubin increased † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Creatinine renal clearance decreased † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Lymphocyte count decreased † 1  7/25 (28.00%)  19 1/15 (6.67%)  2 0/4 (0.00%)  0
Neutrophil count decreased † 1  7/25 (28.00%)  14 2/15 (13.33%)  2 0/4 (0.00%)  0
Platelet count decreased † 1  3/25 (12.00%)  3 2/15 (13.33%)  5 0/4 (0.00%)  0
Thyroid hormones decreased † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Thyroxine free increased † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Tri-iodothyronine free decreased † 1  2/25 (8.00%)  3 0/15 (0.00%)  0 0/4 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite † 1  14/25 (56.00%)  20 9/15 (60.00%)  23 0/4 (0.00%)  0
Hyperglycaemia † 1  2/25 (8.00%)  3 1/15 (6.67%)  1 0/4 (0.00%)  0
Hyperkalaemia † 1  2/25 (8.00%)  3 1/15 (6.67%)  1 0/4 (0.00%)  0
Hyperuricaemia † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Hypoglycaemia † 1  0/25 (0.00%)  0 1/15 (6.67%)  2 0/4 (0.00%)  0
Diabetes mellitus † 1  3/25 (12.00%)  3 0/15 (0.00%)  0 0/4 (0.00%)  0
Hypokalaemia † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Hyponatraemia † 1  3/25 (12.00%)  3 1/15 (6.67%)  1 1/4 (25.00%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Back pain † 1  4/25 (16.00%)  4 2/15 (13.33%)  2 0/4 (0.00%)  0
Myalgia † 1  2/25 (8.00%)  2 0/15 (0.00%)  0 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumour pain † 1  0/25 (0.00%)  0 2/15 (13.33%)  2 0/4 (0.00%)  0
Nervous system disorders       
Dizziness † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Dysgeusia † 1  3/25 (12.00%)  6 5/15 (33.33%)  9 1/4 (25.00%)  1
Headache † 1  1/25 (4.00%)  1 2/15 (13.33%)  3 0/4 (0.00%)  0
Memory impairment † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Peripheral sensory neuropathy † 1  3/25 (12.00%)  3 2/15 (13.33%)  2 0/4 (0.00%)  0
Somnolence † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Psychiatric disorders       
Insomnia † 1  6/25 (24.00%)  8 1/15 (6.67%)  1 0/4 (0.00%)  0
Anxiety † 1  1/25 (4.00%)  2 3/15 (20.00%)  4 0/4 (0.00%)  0
Renal and urinary disorders       
Dysuria † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Renal impairment † 1  0/25 (0.00%)  0 1/15 (6.67%)  2 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Epistaxis † 1  2/25 (8.00%)  2 1/15 (6.67%)  1 0/4 (0.00%)  0
Hiccups † 1  7/25 (28.00%)  11 5/15 (33.33%)  5 1/4 (25.00%)  1
Rhinitis allergic † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders       
Alopecia † 1  4/25 (16.00%)  5 1/15 (6.67%)  1 0/4 (0.00%)  0
Dermatitis acneiform † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Dry skin † 1  9/25 (36.00%)  9 2/15 (13.33%)  2 0/4 (0.00%)  0
Onychoclasis † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Pruritus † 1  1/25 (4.00%)  1 1/15 (6.67%)  1 0/4 (0.00%)  0
Rash † 1  6/25 (24.00%)  6 1/15 (6.67%)  1 1/4 (25.00%)  1
Rash maculo-papular † 1  2/25 (8.00%)  4 1/15 (6.67%)  2 0/4 (0.00%)  0
Vascular disorders       
Deep vein thrombosis † 1  0/25 (0.00%)  0 1/15 (6.67%)  1 0/4 (0.00%)  0
Hypertension † 1  3/25 (12.00%)  4 1/15 (6.67%)  1 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications of Results:
Horinouchi H, Nogami N, Saka H, Nishio M, Tokito T, Takahashi T, Kasahara K, Hattori Y, Ichihara E, Adachi N, Noguchi K, Souza F, Kurata T. Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study. Cancer Sci. 2021 Aug;112(8):3255-3265. doi: 10.1111/cas.14980. Epub 2021 Jun 15.
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: NCT03950674    
Other Study ID Numbers: 3475-189 Japan Extension
163421 ( Registry Identifier: JAPIC-CTI )
MK-3475-189 ( Other Identifier: Merck )
KEYNOTE-189 ( Other Identifier: Merck )
First Submitted: May 13, 2019
First Posted: May 15, 2019
Results First Submitted: May 7, 2020
Results First Posted: June 11, 2020
Last Update Posted: July 20, 2023