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Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)

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ClinicalTrials.gov Identifier: NCT02821000
Recruitment Status : Active, not recruiting
First Posted : July 1, 2016
Results First Posted : March 21, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Intervention Biological: Pembrolizumab
Enrollment 103
Recruitment Details  
Pre-assignment Details This results disclosure is based on a data cutoff date of 27-December-2017 for the efficacy and safety analyses; at which time 58 participants were ongoing in the study. The data cutoff date for the pharmacokinetics analysis was 20-July-2017.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle.
Period Title: Overall Study
Started 103
Treated 103
Completed 0
Not Completed 103
Reason Not Completed
Death             44
Withdrawal by Subject             1
Ongoing in Study             58
Arm/Group Title Pembrolizumab
Hide Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Baseline Participants 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants
50.5  (14.2)
[1]
Measure Analysis Population Description: All enrolled participants
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Female
59
  57.3%
Male
44
  42.7%
[1]
Measure Analysis Population Description: All enrolled participants
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
American Indian or Alaska Native
0
   0.0%
Asian
103
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
[1]
Measure Description: The race of participants is presented.
[2]
Measure Analysis Population Description: All enrolled participants
Programmed Cell Death-Ligand 1 (PD-L1) Expression Status   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Positive for PD-L1
53
  51.5%
Negative for PD-L1
45
  43.7%
Unknown PD-L1 Status
5
   4.9%
[1]
Measure Description: Participants were assessed for their PD-L1 tumor expression status by immunohistochemistry assay using archival tumor tissue or tumor tissue from a newly obtained biopsy. The PD-L1 tumor expression status of participants is presented.
[2]
Measure Analysis Population Description: All enrolled participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
ECOG PS=0
45
  43.7%
ECOG PS=1
58
  56.3%
[1]
Measure Description: Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature; Grade 2: Ambulatory & capable of all selfcare but unable to carry out any work activities, up & about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.
[2]
Measure Analysis Population Description: All enrolled participants
BRAF Mutation Expression Status   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Wild Type
82
  79.6%
Mutant
20
  19.4%
Unknown
1
   1.0%
[1]
Measure Description: BRAF mutation status was required from all participants. For participants that did not have a prior documented BRAF mutation status, BRAF V600 mutation analysis was performed by polymerase chain reaction (PCR) on tumor tissue. The BRAF mutation status of participants is presented.
[2]
Measure Analysis Population Description: All enrolled participants
1.Primary Outcome
Title Number of Participants Who Experienced At Least One Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented. These safety results are based on a 27- Dec-2017 data cutoff date.
Time Frame Up to approximately 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 103
Measure Type: Count of Participants
Unit of Measure: Participants
101
  98.1%
2.Primary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description The number of all participants who discontinued study treatment due to an AE is presented. These results are based on a 27- Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 103
Measure Type: Count of Participants
Unit of Measure: Participants
4
   3.9%
3.Primary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27- Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
16.7
(10.0 to 25.3)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. The OS for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 103
Median (95% Confidence Interval)
Unit of Measure: Months
12.1 [1] 
(9.6 to NA)
[1]
Upper limit for OS not reached
5.Secondary Outcome
Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 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 have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per RECIST 1.1 for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 102
Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.7 to 3.5)
6.Secondary Outcome
Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 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 have demonstrated an absolute increase of at least 5 mm. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 17
Median (Full Range)
Unit of Measure: Months
8.4
(1.1 to 11.0)
7.Secondary Outcome
Title Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Hide Description ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
16.7
(10.0 to 25.3)
8.Secondary Outcome
Title Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Hide Description PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 102
Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.7 to 4.0)
9.Secondary Outcome
Title Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)
Hide Description DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 17
Median (Full Range)
Unit of Measure: Months
8.4
(1.1 to 11.0)
10.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 21: Prior to the Cycle 2 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 1 dose of study treatment, completed Cycle 1 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: μg/mL
8.70  (2.4)
11.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 63: Prior to the Cycle 4 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 3 doses of study treatment, completed Cycle 3 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: μg/mL
16.2  (6.7)
12.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 105: Prior to the Cycle 6 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 5 doses of study treatment, completed Cycle 5 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: μg/mL
22.9  (6.4)
13.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 8 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 8 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 147: Prior to the Cycle 8 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 7 doses of study treatment, completed Cycle 7 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: μg/mL
26.9  (6.5)
14.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 12 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 12 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 231: Prior to the Cycle 12 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 11 doses of study treatment, completed Cycle 11 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: μg/mL
33.8  (4.5)
15.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 16 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 16 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 315: Prior to the Cycle 16 (21-day cycle) Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 15 doses of study treatment, completed Cycle 15 (21-day cycle), and had blood samples drawn for Ctrough analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: μg/mL
34.6  (5.0)
16.Secondary Outcome
Title Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 1 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for Cmax analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: μg/mL
45.9  (10.9)
17.Secondary Outcome
Title Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 8 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 8 doses of study treatment and had blood samples drawn for Cmax analysis.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: μg/mL
68.7  (12.5)
18.Secondary Outcome
Title Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 1 day after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: μg/mL
34.0  (4.6)
19.Secondary Outcome
Title Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 5 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: μg/mL
18.4  (4.6)
20.Secondary Outcome
Title Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle)
Hide Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 14 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
Time Frame Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
Arm/Group Title Pembrolizumab
Hide Arm/Group Description:
Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: μg/mL
11.9  (2.5)
Time Frame Safety data was collected up to 90 days after last dose of study treatment (up to approximately 27 months). The data cutoff date for the safety analysis was 27-December-2017.
Adverse Event Reporting Description The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs.
 
Arm/Group Title Pembrolizumab
Hide Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
All-Cause Mortality
Pembrolizumab
Affected / at Risk (%)
Total   44/103 (42.72%)    
Show Serious Adverse Events Hide Serious Adverse Events
Pembrolizumab
Affected / at Risk (%) # Events
Total   8/103 (7.77%)    
Cardiac disorders   
Sinus tachycardia  1  1/103 (0.97%)  1
Hepatobiliary disorders   
Autoimmune hepatitis  1  1/103 (0.97%)  1
Infections and infestations   
Pneumonia  1  1/103 (0.97%)  1
Injury, poisoning and procedural complications   
Rib fracture  1  1/103 (0.97%)  1
Metabolism and nutrition disorders   
Decreased appetite  1  1/103 (0.97%)  1
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/103 (0.97%)  1
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism  1  1/103 (0.97%)  1
Vascular disorders   
Shock  1  1/103 (0.97%)  1
Venous thrombosis limb  1  1/103 (0.97%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab
Affected / at Risk (%) # Events
Total   98/103 (95.15%)    
Blood and lymphatic system disorders   
Anaemia  1  25/103 (24.27%)  28
Endocrine disorders   
Hyperthyroidism  1  6/103 (5.83%)  6
Hypothyroidism  1  24/103 (23.30%)  30
Gastrointestinal disorders   
Abdominal distension  1  6/103 (5.83%)  6
Abdominal pain upper  1  7/103 (6.80%)  7
Constipation  1  7/103 (6.80%)  8
Diarrhoea  1  7/103 (6.80%)  9
Nausea  1  7/103 (6.80%)  8
Vomiting  1  11/103 (10.68%)  11
General disorders   
Asthenia  1  8/103 (7.77%)  11
Fatigue  1  16/103 (15.53%)  18
Pyrexia  1  10/103 (9.71%)  12
Infections and infestations   
Upper respiratory tract infection  1  14/103 (13.59%)  16
Investigations   
Alanine aminotransferase increased  1  19/103 (18.45%)  24
Aspartate aminotransferase increased  1  15/103 (14.56%)  19
Bilirubin conjugated increased  1  9/103 (8.74%)  14
Blood alkaline phosphatase increased  1  8/103 (7.77%)  9
Blood bilirubin increased  1  16/103 (15.53%)  26
Blood bilirubin unconjugated increased  1  6/103 (5.83%)  10
Blood cholesterol increased  1  6/103 (5.83%)  11
Blood creatine phosphokinase increased  1  9/103 (8.74%)  11
Blood lactate dehydrogenase increased  1  16/103 (15.53%)  25
Gamma-glutamyltransferase increased  1  13/103 (12.62%)  14
Neutrophil count decreased  1  10/103 (9.71%)  16
Total bile acids increased  1  6/103 (5.83%)  12
Weight decreased  1  11/103 (10.68%)  11
White blood cell count decreased  1  13/103 (12.62%)  23
White blood cells urine positive  1  7/103 (6.80%)  7
Metabolism and nutrition disorders   
Decreased appetite  1  18/103 (17.48%)  19
Hypercholesterolaemia  1  6/103 (5.83%)  12
Hyperglycaemia  1  12/103 (11.65%)  23
Hypertriglyceridaemia  1  27/103 (26.21%)  58
Hyperuricaemia  1  13/103 (12.62%)  21
Hypoalbuminaemia  1  9/103 (8.74%)  11
Hyponatraemia  1  8/103 (7.77%)  8
Musculoskeletal and connective tissue disorders   
Back pain  1  9/103 (8.74%)  9
Pain in extremity  1  6/103 (5.83%)  8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour pain  1  18/103 (17.48%)  24
Psychiatric disorders   
Insomnia  1  8/103 (7.77%)  8
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/103 (8.74%)  10
Dyspnoea  1  6/103 (5.83%)  6
Skin and subcutaneous tissue disorders   
Pruritus  1  14/103 (13.59%)  16
Rash  1  18/103 (17.48%)  20
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
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02821000     History of Changes
Other Study ID Numbers: 3475-151
MK-3475-151 ( Other Identifier: Merck Protocol Number )
KEYNOTE-151 ( Other Identifier: Merck )
First Submitted: June 29, 2016
First Posted: July 1, 2016
Results First Submitted: December 10, 2018
Results First Posted: March 21, 2019
Last Update Posted: June 26, 2019