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A Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With First Line Metastatic Squamous Non-small Cell Lung Cancer (MK-3475-407/KEYNOTE-407)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02775435
Recruitment Status : Active, not recruiting
First Posted : May 17, 2016
Results First Posted : April 10, 2019
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Biological: Pembrolizumab
Drug: Paclitaxel
Drug: Nab-paclitaxel
Drug: Carboplatin
Drug: Saline placebo for pembrolizumab
Enrollment 559
Recruitment Details Interim analysis data cutoff date: 03-Apr-2018. Of the 559 randomized participants, 193 were ongoing and 75 participants randomized to chemotherapy had switched to receiving protocol-specified pembrolizumab (MK-3475). Interim results are for randomized treatment only.
Pre-assignment Details  
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description Participants received pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles. Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Period Title: Overall Study
Started 278 281
Treated 278 280
Switched to Pembrolizumab+Chemotherapy 0 75
Completed 0 0
Not Completed 278 281
Reason Not Completed
Adverse Event             48             25
Lost to Follow-up             0             2
Physician Decision             5             6
Withdrawal by Subject             5             9
Progressive Disease             86             140
Clinical Progression             13             26
Ongoing in Study             121             72
Not Treated             0             1
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy Total
Hide Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles. Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles. Total of all reporting groups
Overall Number of Baseline Participants 278 281 559
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 278 participants 281 participants 559 participants
65.0  (8.8) 64.8  (8.7) 64.9  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 281 participants 559 participants
Female
58
  20.9%
46
  16.4%
104
  18.6%
Male
220
  79.1%
235
  83.6%
455
  81.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 281 participants 559 participants
American Indian or Alaska Native
0
   0.0%
2
   0.7%
2
   0.4%
Asian
56
  20.1%
52
  18.5%
108
  19.3%
Native Hawaiian or Other Pacific Islander
1
   0.4%
0
   0.0%
1
   0.2%
Black or African American
3
   1.1%
4
   1.4%
7
   1.3%
White
216
  77.7%
214
  76.2%
430
  76.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   0.7%
9
   3.2%
11
   2.0%
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 281 participants 559 participants
TPS <1%
95
  34.2%
99
  35.2%
194
  34.7%
TPS ≥1%
176
  63.3%
177
  63.0%
353
  63.1%
Unknown
7
   2.5%
5
   1.8%
12
   2.1%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a TPS ≥1% were classified as PD-L1 positive and participants with a TPS <1% were classified as not PD-L1 positive.
Taxane Chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 281 participants 559 participants
+Paclitaxel
169
  60.8%
167
  59.4%
336
  60.1%
+Nab-paclitaxel
109
  39.2%
114
  40.6%
223
  39.9%
[1]
Measure Description: Participants were classified according to their taxane chemotherapy regimen: paclitaxel or nab-paclitaxel.
Geographic Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 281 participants 559 participants
East Asia
54
  19.4%
52
  18.5%
106
  19.0%
Non-East Asia
224
  80.6%
229
  81.5%
453
  81.0%
[1]
Measure Description: Participants were classified according to their geographic region: East Asia vs. non-East Asia.
1.Primary Outcome
Title Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (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 ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 278 281
Median (95% Confidence Interval)
Unit of Measure: Months
6.4
(6.2 to 8.3)
4.8
(4.2 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Treatment as a covariate stratified by programmed cell death-ligand 1 (PD-L1) status (Tumor Proportion Score [TPS] ≥1% vs. <1%), taxane chemotherapy (paclitaxel vs. nab-paclitaxel) & geographic region (East Asia vs. non-East Asia)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.45 to 0.70
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. OS is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 278 281
Median (95% Confidence Interval)
Unit of Measure: Months
15.9 [1] 
(13.2 to NA)
11.3
(9.5 to 14.8)
[1]
NA=OS upper limit not reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments Treatment as a covariate stratified by programmed cell death-ligand 1 (PD-L1) status (Tumor Proportion Score [TPS] ≥1% vs. <1%), taxane chemotherapy (paclitaxel vs. nab-paclitaxel) & geographic region (East Asia vs. non-East Asia)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.49 to 0.85
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment arm to which they were randomized.
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 278 281
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
57.9
(51.9 to 63.8)
38.4
(32.7 to 44.4)
4.Secondary Outcome
Title Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description For participants who demonstrated a confirmed response (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) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. DOR as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat population consisted of 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 Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 161 108
Median (Full Range)
Unit of Measure: Months
7.7
(1.1 to 14.7)
4.8
(1.3 to 15.8)
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 participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 278 280
Measure Type: Count of Participants
Unit of Measure: Participants
273
  98.2%
274
  97.9%
6.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Hide Description The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Pembrolizumab + Chemotherapy Chemotherapy
Hide Arm/Group Description:
Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed 278 280
Measure Type: Count of Participants
Unit of Measure: Participants
65
  23.4%
33
  11.8%
Time Frame Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Adverse Event Reporting Description Safety Population: All participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs.
 
Arm/Group Title Pembrolizumab+Chemotherapy Chemotherapy
Hide Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles. Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator’s choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
All-Cause Mortality
Pembrolizumab+Chemotherapy Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   85/278 (30.58%)      120/281 (42.70%)    
Hide Serious Adverse Events
Pembrolizumab+Chemotherapy Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   113/278 (40.65%)      107/280 (38.21%)    
Blood and lymphatic system disorders     
Anaemia  1  5/278 (1.80%)  5 8/280 (2.86%)  9
Eosinophilia  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Febrile neutropenia  1  15/278 (5.40%)  15 10/280 (3.57%)  12
Leukopenia  1  3/278 (1.08%)  3 0/280 (0.00%)  0
Neutropenia  1  4/278 (1.44%)  5 7/280 (2.50%)  8
Thrombocytopenia  1  5/278 (1.80%)  6 3/280 (1.07%)  4
Cardiac disorders     
Acute coronary syndrome  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Atrial fibrillation  1  0/278 (0.00%)  0 2/280 (0.71%)  3
Atrial flutter  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Cardiac arrest  1  2/278 (0.72%)  2 2/280 (0.71%)  2
Cardiac failure  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Cardio-respiratory arrest  1  0/278 (0.00%)  0 2/280 (0.71%)  2
Myocardial infarction  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Pericardial effusion  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Prinzmetal angina  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Tachycardia  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Endocrine disorders     
Autoimmune thyroiditis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hyperthyroidism  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hypophysitis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hypopituitarism  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hypothyroidism  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Colitis  1  6/278 (2.16%)  6 1/280 (0.36%)  1
Diarrhoea  1  7/278 (2.52%)  7 6/280 (2.14%)  6
Duodenal ulcer  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Duodenitis  1  2/278 (0.72%)  3 0/280 (0.00%)  0
Enterocolitis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Gastric ulcer haemorrhage  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Ileus  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Intestinal perforation  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Nausea  1  0/278 (0.00%)  0 2/280 (0.71%)  2
Pneumatosis intestinalis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Vomiting  1  0/278 (0.00%)  0 3/280 (1.07%)  4
General disorders     
Asthenia  1  1/278 (0.36%)  1 5/280 (1.79%)  5
Chest pain  1  1/278 (0.36%)  1 2/280 (0.71%)  2
Death  1  4/278 (1.44%)  4 3/280 (1.07%)  3
Fatigue  1  1/278 (0.36%)  1 3/280 (1.07%)  3
General physical health deterioration  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Malaise  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Multiple organ dysfunction syndrome  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Oedema peripheral  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Pyrexia  1  6/278 (2.16%)  7 3/280 (1.07%)  3
Hepatobiliary disorders     
Autoimmune hepatitis  1  2/278 (0.72%)  2 0/280 (0.00%)  0
Cholangitis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Cholecystitis acute  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Cholelithiasis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hepatic failure  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Immune system disorders     
Amyloidosis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Drug hypersensitivity  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Infections and infestations     
Appendiceal abscess  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Biliary tract infection  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Blister infected  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Bronchitis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Candida infection  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Clostridium difficile colitis  1  1/278 (0.36%)  4 0/280 (0.00%)  0
Device related infection  1  0/278 (0.00%)  0 2/280 (0.71%)  2
Empyema  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Hepatitis viral  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Kidney infection  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Lower respiratory tract infection  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Lung abscess  1  2/278 (0.72%)  3 0/280 (0.00%)  0
Lung infection  1  3/278 (1.08%)  3 2/280 (0.71%)  2
Meningitis pneumococcal  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Necrotising fasciitis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Oral candidiasis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Pneumonia  1  16/278 (5.76%)  17 17/280 (6.07%)  19
Pneumonia bacterial  1  2/278 (0.72%)  2 1/280 (0.36%)  1
Pneumonia klebsiella  1  0/278 (0.00%)  0 1/280 (0.36%)  3
Pneumonia legionella  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Prostatic abscess  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Pulmonary mycosis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Pulmonary sepsis  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Pyelonephritis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Sepsis  1  5/278 (1.80%)  5 2/280 (0.71%)  2
Septic shock  1  1/278 (0.36%)  1 3/280 (1.07%)  3
Upper respiratory tract infection  1  2/278 (0.72%)  3 0/280 (0.00%)  0
Urinary tract infection  1  2/278 (0.72%)  2 1/280 (0.36%)  1
Urosepsis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Injury, poisoning and procedural complications     
Infusion related reaction  1  4/278 (1.44%)  5 1/280 (0.36%)  1
Spinal compression fracture  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Neutrophil count decreased  1  3/278 (1.08%)  3 1/280 (0.36%)  1
Platelet count decreased  1  1/278 (0.36%)  1 0/280 (0.00%)  0
White blood cell count decreased  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  1/278 (0.36%)  1 2/280 (0.71%)  2
Dehydration  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Diabetes mellitus  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Hypercalcaemia  1  0/278 (0.00%)  0 4/280 (1.43%)  4
Hyperkalaemia  1  1/278 (0.36%)  1 2/280 (0.71%)  2
Hyponatraemia  1  2/278 (0.72%)  3 2/280 (0.71%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/278 (0.72%)  2 0/280 (0.00%)  0
Back pain  1  2/278 (0.72%)  2 1/280 (0.36%)  1
Muscle haemorrhage  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Myalgia  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Colon cancer  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Squamous cell carcinoma of skin  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Transitional cell carcinoma  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Tumour necrosis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Nervous system disorders     
Carotid artery stenosis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Cerebral infarction  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Cerebral ischaemia  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Cerebrovascular accident  1  2/278 (0.72%)  2 0/280 (0.00%)  0
Depressed level of consciousness  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Dizziness  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Epilepsy  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Headache  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Intercostal neuralgia  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Ischaemic stroke  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Neuropathy peripheral  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Sciatica  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Seizure  1  2/278 (0.72%)  2 0/280 (0.00%)  0
Spinal cord compression  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Syncope  1  1/278 (0.36%)  1 3/280 (1.07%)  3
Transient ischaemic attack  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Uraemic encephalopathy  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Psychiatric disorders     
Confusional state  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Delirium  1  1/278 (0.36%)  1 2/280 (0.71%)  2
Renal and urinary disorders     
Acute kidney injury  1  2/278 (0.72%)  3 4/280 (1.43%)  4
Glomerulonephritis membranous  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Nephritis  1  1/278 (0.36%)  2 1/280 (0.36%)  1
Tubulointerstitial nephritis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Bronchitis chronic  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Chronic obstructive pulmonary disease  1  2/278 (0.72%)  2 2/280 (0.71%)  2
Dyspnoea  1  0/278 (0.00%)  0 3/280 (1.07%)  3
Epistaxis  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Haemoptysis  1  5/278 (1.80%)  5 4/280 (1.43%)  4
Haemothorax  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Hypoxia  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Interstitial lung disease  1  2/278 (0.72%)  2 2/280 (0.71%)  2
Obstructive airways disorder  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Pleural effusion  1  3/278 (1.08%)  4 2/280 (0.71%)  3
Pneumonia aspiration  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Pneumonitis  1  7/278 (2.52%)  7 2/280 (0.71%)  2
Pneumothorax  1  2/278 (0.72%)  2 1/280 (0.36%)  1
Pulmonary embolism  1  2/278 (0.72%)  2 3/280 (1.07%)  3
Pulmonary haemorrhage  1  3/278 (1.08%)  3 2/280 (0.71%)  2
Pulmonary oedema  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Respiratory failure  1  3/278 (1.08%)  3 0/280 (0.00%)  0
Skin and subcutaneous tissue disorders     
Diabetic foot  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Psoriasis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Rash maculo-papular  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Vascular disorders     
Arterial disorder  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Circulatory collapse  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Deep vein thrombosis  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Embolism  1  1/278 (0.36%)  1 1/280 (0.36%)  1
Hypotension  1  2/278 (0.72%)  2 3/280 (1.07%)  3
Orthostatic hypotension  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Superior vena cava syndrome  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Thrombophlebitis superficial  1  1/278 (0.36%)  1 0/280 (0.00%)  0
Trousseau's syndrome  1  0/278 (0.00%)  0 1/280 (0.36%)  1
Vasculitis  1  1/278 (0.36%)  1 0/280 (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+Chemotherapy Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   268/278 (96.40%)      267/280 (95.36%)    
Blood and lymphatic system disorders     
Anaemia  1  144/278 (51.80%)  180 138/280 (49.29%)  170
Leukopenia  1  22/278 (7.91%)  57 20/280 (7.14%)  35
Neutropenia  1  101/278 (36.33%)  205 86/280 (30.71%)  160
Thrombocytopenia  1  80/278 (28.78%)  127 64/280 (22.86%)  87
Endocrine disorders     
Hyperthyroidism  1  19/278 (6.83%)  19 2/280 (0.71%)  2
Hypothyroidism  1  21/278 (7.55%)  21 5/280 (1.79%)  5
Gastrointestinal disorders     
Abdominal pain  1  19/278 (6.83%)  21 15/280 (5.36%)  15
Constipation  1  64/278 (23.02%)  82 61/280 (21.79%)  73
Diarrhoea  1  77/278 (27.70%)  111 59/280 (21.07%)  75
Nausea  1  99/278 (35.61%)  140 88/280 (31.43%)  129
Vomiting  1  45/278 (16.19%)  56 30/280 (10.71%)  45
General disorders     
Asthenia  1  59/278 (21.22%)  79 54/280 (19.29%)  63
Chest pain  1  15/278 (5.40%)  15 20/280 (7.14%)  20
Fatigue  1  63/278 (22.66%)  82 69/280 (24.64%)  97
Oedema peripheral  1  21/278 (7.55%)  22 20/280 (7.14%)  27
Pyrexia  1  30/278 (10.79%)  33 36/280 (12.86%)  42
Infections and infestations     
Bronchitis  1  17/278 (6.12%)  17 10/280 (3.57%)  10
Upper respiratory tract infection  1  14/278 (5.04%)  16 10/280 (3.57%)  13
Investigations     
Alanine aminotransferase increased  1  14/278 (5.04%)  23 11/280 (3.93%)  11
Aspartate aminotransferase increased  1  19/278 (6.83%)  28 12/280 (4.29%)  12
Blood creatinine increased  1  21/278 (7.55%)  22 14/280 (5.00%)  19
Neutrophil count decreased  1  21/278 (7.55%)  43 27/280 (9.64%)  57
Platelet count decreased  1  24/278 (8.63%)  32 20/280 (7.14%)  38
Weight decreased  1  28/278 (10.07%)  28 21/280 (7.50%)  21
White blood cell count decreased  1  30/278 (10.79%)  58 30/280 (10.71%)  55
Metabolism and nutrition disorders     
Decreased appetite  1  68/278 (24.46%)  104 81/280 (28.93%)  99
Hypocalcaemia  1  6/278 (2.16%)  9 15/280 (5.36%)  19
Hypokalaemia  1  17/278 (6.12%)  19 17/280 (6.07%)  20
Hypomagnesaemia  1  23/278 (8.27%)  30 20/280 (7.14%)  22
Musculoskeletal and connective tissue disorders     
Arthralgia  1  55/278 (19.78%)  78 40/280 (14.29%)  49
Back pain  1  14/278 (5.04%)  14 31/280 (11.07%)  31
Musculoskeletal pain  1  22/278 (7.91%)  25 13/280 (4.64%)  13
Myalgia  1  37/278 (13.31%)  46 34/280 (12.14%)  40
Pain in extremity  1  24/278 (8.63%)  33 25/280 (8.93%)  33
Nervous system disorders     
Dizziness  1  17/278 (6.12%)  20 19/280 (6.79%)  21
Dysgeusia  1  25/278 (8.99%)  27 11/280 (3.93%)  11
Headache  1  19/278 (6.83%)  20 21/280 (7.50%)  24
Neuropathy peripheral  1  56/278 (20.14%)  61 45/280 (16.07%)  53
Paraesthesia  1  18/278 (6.47%)  19 15/280 (5.36%)  16
Peripheral sensory neuropathy  1  32/278 (11.51%)  33 36/280 (12.86%)  37
Psychiatric disorders     
Insomnia  1  28/278 (10.07%)  29 23/280 (8.21%)  26
Respiratory, thoracic and mediastinal disorders     
Cough  1  37/278 (13.31%)  41 47/280 (16.79%)  54
Dyspnoea  1  36/278 (12.95%)  37 42/280 (15.00%)  44
Epistaxis  1  27/278 (9.71%)  31 18/280 (6.43%)  20
Haemoptysis  1  21/278 (7.55%)  21 26/280 (9.29%)  37
Skin and subcutaneous tissue disorders     
Alopecia  1  128/278 (46.04%)  128 102/280 (36.43%)  102
Pruritus  1  36/278 (12.95%)  40 21/280 (7.50%)  25
Rash  1  39/278 (14.03%)  47 28/280 (10.00%)  32
Vascular disorders     
Hypotension  1  11/278 (3.96%)  12 15/280 (5.36%)  16
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02775435    
Other Study ID Numbers: 3475-407
2016-000229-38 ( EudraCT Number )
173568 ( Registry Identifier: JAPIC-CTI )
MK-3475-407 ( Other Identifier: Merck Protocol Number )
KEYNOTE-407 ( Other Identifier: Merck )
First Submitted: May 15, 2016
First Posted: May 17, 2016
Results First Submitted: February 19, 2019
Results First Posted: April 10, 2019
Last Update Posted: April 1, 2020