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Study of Pembrolizumab (MK-3475) Monotherapy for Metastatic Triple-Negative Breast Cancer (MK-3475-086/KEYNOTE-086)

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: NCT02447003
Recruitment Status : Completed
First Posted : May 18, 2015
Results First Posted : December 16, 2020
Last Update Posted : December 16, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Intervention Biological: Pembrolizumab
Enrollment 254
Recruitment Details  
Pre-assignment Details

Per protocol, response or progression during the second pembrolizumab course was not counted towards efficacy outcome measures, and adverse events during the second pembrolizumab course were not counted towards safety outcome measures.

Based on protocol-specified inclusion criteria and outcome analyses requirements, Part 2 was not conducted.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).
Period Title: Overall Study
Started 170 84
Completed 0 0
Not Completed 170 84
Reason Not Completed
Other             0             4
Site discontinued             0             2
Physician Decision             0             1
Withdrawal by Subject             4             3
Sponsor Decision             6             11
Progressive Disease             1             0
Lost to Follow-up             5             0
Death             154             63
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab Total
Hide Arm/Group Description Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). Total of all reporting groups
Overall Number of Baseline Participants 170 84 254
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 170 participants 84 participants 254 participants
54.6  (12.8) 54.2  (14.1) 54.5  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 84 participants 254 participants
Female
170
 100.0%
84
 100.0%
254
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 84 participants 254 participants
Hispanic or Latino
10
   5.9%
6
   7.1%
16
   6.3%
Not Hispanic or Latino
146
  85.9%
74
  88.1%
220
  86.6%
Unknown or Not Reported
14
   8.2%
4
   4.8%
18
   7.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 84 participants 254 participants
American Indian or Alaska Native
1
   0.6%
0
   0.0%
1
   0.4%
Asian
24
  14.1%
15
  17.9%
39
  15.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
12
   7.1%
14
  16.7%
26
  10.2%
White
129
  75.9%
53
  63.1%
182
  71.7%
More than one race
3
   1.8%
0
   0.0%
3
   1.2%
Unknown or Not Reported
1
   0.6%
2
   2.4%
3
   1.2%
1.Primary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants
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: ≥30% decrease in sum of diameters [SOD] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of final statistical efficacy analysis, with a 10-November (Nov)-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was planned and conducted as a pre-specified primary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol ORR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A who got ≥1 dose of study drug. Per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants as a pre-specified secondary outcome analysis and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.3
(2.7 to 9.9)
2.Primary Outcome
Title ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression
Hide Description ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol ORR for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants as a pre-specified secondary outcome analysis and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 105 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.7
(2.4 to 12.2)
3.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 clinical investigation participant administered a pharmaceutical product 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. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first pembrolizumab course, was assessed from enrollment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.
Time Frame Up to ~31 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol participants who experienced AEs, for the first pembrolizumab course, were analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 84
Measure Type: Count of Participants
Unit of Measure: Participants
161
  94.7%
83
  98.8%
4.Primary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE
Hide Description An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product 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. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in the first pembrolizumab course, was assessed from enrolment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.
Time Frame Up to ~31 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol participants who discontinued study drug due to an AE, for the first pembrolizumab course, were analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 84
Measure Type: Count of Participants
Unit of Measure: Participants
8
   4.7%
3
   3.6%
5.Secondary Outcome
Title ORR Per RECIST 1.1 by CIV in All Cohort B Participants
Hide Description ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for all participants in Cohort B. Per protocol final ORR analysis in all Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was planned and conducted as a pre-specified secondary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was analyzed separately as a pre-specified primary outcome analysis and reported earlier in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol ORR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort B who got ≥1 dose of study drug. Per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort A participants as a pre-specified primary outcome analysis and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 0 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
21.4
(13.9 to 31.4)
6.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants
Hide Description For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until progressive disease (PD: ≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by Kaplan-Meier (KM) method and analyzed by cohort is reported here for all participants in Cohort A and Cohort B who had CR or PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol DOR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who had CR or PR per RECIST 1.1 by CIV and got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 9 18
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
10.4 [2] 
(4.2 to NA)
[1]
Median and range lower and upper limit not reached (no progressive disease by the time of last disease assessment)
[2]
Range upper limit not reached (no progressive disease by the time of last disease assessment)
7.Secondary Outcome
Title DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression
Hide Description For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until PD (≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by KM method and analyzed by Cohort is reported here for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+) and CR/PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in Cohort A PD-L1+ subgroup was done at time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DOR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol DOR, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+, had CR or PR per RECIST 1.1 by CIV and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol DOR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 6 0
Median (Full Range)
Unit of Measure: Months
NA [1] 
(6.3 to NA)
[1]
Median and range upper limit not reached (no progressive disease by the time of last disease assessment)
8.Secondary Outcome
Title Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants
Hide Description DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR, for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort, for all participants in Cohort A and Cohort B. Per protocol final DCR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol DCR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
7.6
(4.4 to 12.7)
23.8
(15.9 to 34.0)
9.Secondary Outcome
Title DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression
Hide Description DCR was defined as the percentage of participants who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final DCR analysis in Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DCR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol DCR, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol DCR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 105 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
9.5
(5.1 to 16.8)
10.Secondary Outcome
Title Progression Free Survival (PFS) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants
Hide Description PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final PFS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff.
Time Frame Up to ~28 months (through pre-specified final statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol PFS, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 84
Median (95% Confidence Interval)
Unit of Measure: Months
2.0
(1.9 to 2.0)
2.1
(2.0 to 2.2)
11.Secondary Outcome
Title PFS Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression
Hide Description PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final PFS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and PFS per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol PFS, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol PFS per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 105 0
Median (95% Confidence Interval)
Unit of Measure: Months
2.0
(1.9 to 2.1)
12.Secondary Outcome
Title Overall Survival (OS) in All Cohort A and Cohort B Participants
Hide Description OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final OS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
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Hide Analysis Population Description
Per protocol OS, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 170 84
Median (95% Confidence Interval)
Unit of Measure: Months
9.0
(7.6 to 11.2)
18.0
(12.9 to 23.0)
13.Secondary Outcome
Title OS in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression
Hide Description OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final OS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and OS in all Cohort B participants was analyzed separately and reported earlier in the record.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol OS for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol OS was analyzed separately in all Cohort B participants and is not included in this analysis.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 105 0
Median (95% Confidence Interval)
Unit of Measure: Months
8.8
(7.1 to 11.2)
14.Secondary Outcome
Title Odds Ratio of Association Between PD-L1 Tumor Expression and Objective Response (OR) Per RECIST 1.1 by CIV in Cohort A Participants
Hide Description OR comprises CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV. PD-L1 expression is assessed by IHC-defined combined positive score (CPS). Association between (b/w) PD-L1 CPS and OR was assessed by odds ratio using a logistic regression model and was calculated as ratio of odds of OR per unit CPS increase in a single arm (odds ratio=1: no association; odds ratio<1: negative association [increase in CPS lowers odds of OR]; odds ratio >1: positive association [increase in CPS raises odds of OR]). Per protocol odds ratio, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here in a single arm of Cohort A participants with PD-L1 CPS available. Per protocol odds ratio was analyzed at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol odds ratio of association b/w PD-L1 expression and OR was not planned or done in Cohort B participants.
Time Frame Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol odds ratio, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A who got ≥1 dose of study drug and had CPS for PD-L1 available. Per protocol odds ratio of association b/w PD-L1 expression and OR was not planned or conducted in cohort B participants.
Arm/Group Title Cohort A: Pembrolizumab Cohort B: Pembrolizumab
Hide Arm/Group Description:
Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years).
Overall Number of Participants Analyzed 169 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Odds Ratio
1.017
(0.991 to 1.043)
Time Frame Safety: Up to ~31 months for pembrolizumab first course and up to additional ~15 months for pembrolizumab second course (AEs were collected through 90 days post treatment for SAEs and 30 days post treatment for NSAEs); All-cause mortality (ACM): Up to ~54 months for pembrolizumab first and second course
Adverse Event Reporting Description Safety and ACM were analyzed by Cohort (A and B) and by Course of pembrolizumab (first and second course) in all participants who got ≥1 dose of study drug, and were assessed from a participant's enrolment/treatment initiation. Per protocol disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
 
Arm/Group Title Cohort A: Pembrolizumab First Course Cohort A: Pembrolizumab Second Course Cohort B: Pembrolizumab First Course Cohort B: Pembrolizumab Second Course
Hide Arm/Group Description Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified Cohort A participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W) for up to 17 cycles (up to ~1 year). Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified Cohort B participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 17 cycles (up to ~1 year).
All-Cause Mortality
Cohort A: Pembrolizumab First Course Cohort A: Pembrolizumab Second Course Cohort B: Pembrolizumab First Course Cohort B: Pembrolizumab Second Course
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   154/170 (90.59%)      0/1 (0.00%)      63/84 (75.00%)      0/4 (0.00%)    
Hide Serious Adverse Events
Cohort A: Pembrolizumab First Course Cohort A: Pembrolizumab Second Course Cohort B: Pembrolizumab First Course Cohort B: Pembrolizumab Second Course
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   46/170 (27.06%)      0/1 (0.00%)      19/84 (22.62%)      2/4 (50.00%)    
Blood and lymphatic system disorders         
Anaemia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Febrile neutropenia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Cardiac disorders         
Cardiac tamponade † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Myocarditis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pericardial effusion † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Pericarditis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders         
Colitis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Constipation † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Diarrhoea † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Gastroenteritis eosinophilic † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Intestinal obstruction † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Nausea † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Subileus † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
General disorders         
General physical health deterioration † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pain † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Pyrexia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Hepatobiliary disorders         
Cholangitis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Hepatocellular injury † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations         
Appendicitis † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Bacteraemia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Infected skin ulcer † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Lower respiratory tract infection † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pneumonia † 1  5/170 (2.94%)  7 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Sepsis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Septic shock † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Staphylococcal infection † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Superinfection † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Urinary tract infection † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Wound infection † 1  1/170 (0.59%)  2 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications         
Humerus fracture † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Infusion related reaction † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Postoperative ileus † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 0/84 (0.00%)  0 1/4 (25.00%)  1
Investigations         
Blood alkaline phosphatase increased † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Blood bilirubin increased † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Liver function test abnormal † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders         
Diabetic ketoacidosis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Hyperglycaemia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Hyponatraemia † 1  2/170 (1.18%)  3 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Flank pain † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Intervertebral disc protrusion † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal pain † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pain in extremity † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Rheumatoid arthritis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cancer pain † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Colorectal cancer † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Infected neoplasm † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Neoplasm malignant † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Squamous cell carcinoma † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Nervous system disorders         
Encephalopathy † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Headache † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Intracranial pressure increased † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Loss of consciousness † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Migraine † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Product Issues         
Device failure † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Renal failure † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  2/170 (1.18%)  3 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Hypoxia † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pleural effusion † 1  8/170 (4.71%)  8 0/1 (0.00%)  0 3/84 (3.57%)  5 0/4 (0.00%)  0
Pneumonitis † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pneumothorax † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pulmonary embolism † 1  3/170 (1.76%)  3 0/1 (0.00%)  0 0/84 (0.00%)  0 1/4 (25.00%)  1
Pulmonary oedema † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Pulmonary thrombosis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders         
Drug eruption † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
Vascular disorders         
Deep vein thrombosis † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 0/4 (0.00%)  0
Hypotension † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: Pembrolizumab First Course Cohort A: Pembrolizumab Second Course Cohort B: Pembrolizumab First Course Cohort B: Pembrolizumab Second Course
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   147/170 (86.47%)      1/1 (100.00%)      79/84 (94.05%)      4/4 (100.00%)    
Blood and lymphatic system disorders         
Anaemia † 1  18/170 (10.59%)  22 0/1 (0.00%)  0 10/84 (11.90%)  12 0/4 (0.00%)  0
Endocrine disorders         
Hyperthyroidism † 1  9/170 (5.29%)  9 0/1 (0.00%)  0 4/84 (4.76%)  5 0/4 (0.00%)  0
Hypothyroidism † 1  19/170 (11.18%)  20 0/1 (0.00%)  0 9/84 (10.71%)  10 1/4 (25.00%)  1
Eye disorders         
Vision blurred † 1  3/170 (1.76%)  3 0/1 (0.00%)  0 5/84 (5.95%)  5 0/4 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain † 1  8/170 (4.71%)  8 0/1 (0.00%)  0 9/84 (10.71%)  14 1/4 (25.00%)  1
Constipation † 1  33/170 (19.41%)  36 0/1 (0.00%)  0 9/84 (10.71%)  11 0/4 (0.00%)  0
Diarrhoea † 1  22/170 (12.94%)  32 0/1 (0.00%)  0 16/84 (19.05%)  24 1/4 (25.00%)  1
Dry mouth † 1  11/170 (6.47%)  11 0/1 (0.00%)  0 2/84 (2.38%)  2 0/4 (0.00%)  0
Nausea † 1  34/170 (20.00%)  41 0/1 (0.00%)  0 23/84 (27.38%)  29 0/4 (0.00%)  0
Vomiting † 1  19/170 (11.18%)  24 0/1 (0.00%)  0 11/84 (13.10%)  21 0/4 (0.00%)  0
General disorders         
Asthenia † 1  19/170 (11.18%)  20 0/1 (0.00%)  0 8/84 (9.52%)  9 1/4 (25.00%)  1
Chest pain † 1  11/170 (6.47%)  13 0/1 (0.00%)  0 6/84 (7.14%)  7 0/4 (0.00%)  0
Fatigue † 1  49/170 (28.82%)  59 0/1 (0.00%)  0 30/84 (35.71%)  40 1/4 (25.00%)  1
Oedema peripheral † 1  15/170 (8.82%)  18 0/1 (0.00%)  0 7/84 (8.33%)  8 0/4 (0.00%)  0
Pain † 1  5/170 (2.94%)  5 0/1 (0.00%)  0 5/84 (5.95%)  5 0/4 (0.00%)  0
Pyrexia † 1  19/170 (11.18%)  25 0/1 (0.00%)  0 10/84 (11.90%)  12 1/4 (25.00%)  1
Infections and infestations         
Upper respiratory tract infection † 1  6/170 (3.53%)  8 0/1 (0.00%)  0 6/84 (7.14%)  6 0/4 (0.00%)  0
Urinary tract infection † 1  4/170 (2.35%)  4 0/1 (0.00%)  0 7/84 (8.33%)  7 1/4 (25.00%)  1
Pneumonia † 1  3/170 (1.76%)  3 0/1 (0.00%)  0 1/84 (1.19%)  1 1/4 (25.00%)  1
Investigations         
Alanine aminotransferase increased † 1  6/170 (3.53%)  7 0/1 (0.00%)  0 6/84 (7.14%)  7 1/4 (25.00%)  1
Aspartate aminotransferase increased † 1  12/170 (7.06%)  14 0/1 (0.00%)  0 8/84 (9.52%)  9 1/4 (25.00%)  1
Weight decreased † 1  10/170 (5.88%)  10 0/1 (0.00%)  0 4/84 (4.76%)  4 0/4 (0.00%)  0
Platelet count decreased † 1  3/170 (1.76%)  3 0/1 (0.00%)  0 1/84 (1.19%)  1 1/4 (25.00%)  1
Weight increased † 1  1/170 (0.59%)  1 1/1 (100.00%)  1 1/84 (1.19%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite † 1  28/170 (16.47%)  30 0/1 (0.00%)  0 12/84 (14.29%)  14 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  29/170 (17.06%)  38 0/1 (0.00%)  0 15/84 (17.86%)  20 0/4 (0.00%)  0
Back pain † 1  17/170 (10.00%)  17 0/1 (0.00%)  0 16/84 (19.05%)  19 0/4 (0.00%)  0
Musculoskeletal chest pain † 1  13/170 (7.65%)  14 0/1 (0.00%)  0 4/84 (4.76%)  4 0/4 (0.00%)  0
Musculoskeletal pain † 1  12/170 (7.06%)  14 0/1 (0.00%)  0 6/84 (7.14%)  7 0/4 (0.00%)  0
Myalgia † 1  12/170 (7.06%)  14 0/1 (0.00%)  0 9/84 (10.71%)  10 0/4 (0.00%)  0
Pain in extremity † 1  15/170 (8.82%)  18 1/1 (100.00%)  1 7/84 (8.33%)  9 0/4 (0.00%)  0
Nervous system disorders         
Dizziness † 1  11/170 (6.47%)  11 0/1 (0.00%)  0 10/84 (11.90%)  11 0/4 (0.00%)  0
Headache † 1  13/170 (7.65%)  16 0/1 (0.00%)  0 16/84 (19.05%)  18 0/4 (0.00%)  0
Paraesthesia † 1  4/170 (2.35%)  4 0/1 (0.00%)  0 9/84 (10.71%)  11 0/4 (0.00%)  0
Psychiatric disorders         
Anxiety † 1  11/170 (6.47%)  11 0/1 (0.00%)  0 3/84 (3.57%)  3 0/4 (0.00%)  0
Depression † 1  8/170 (4.71%)  8 0/1 (0.00%)  0 5/84 (5.95%)  5 0/4 (0.00%)  0
Insomnia † 1  6/170 (3.53%)  6 0/1 (0.00%)  0 7/84 (8.33%)  7 0/4 (0.00%)  0
Renal and urinary disorders         
Haematuria † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 0/84 (0.00%)  0 1/4 (25.00%)  1
Respiratory, thoracic and mediastinal disorders         
Cough † 1  39/170 (22.94%)  45 0/1 (0.00%)  0 20/84 (23.81%)  22 2/4 (50.00%)  2
Dyspnoea † 1  25/170 (14.71%)  26 0/1 (0.00%)  0 17/84 (20.24%)  21 1/4 (25.00%)  1
Pleural effusion † 1  9/170 (5.29%)  11 0/1 (0.00%)  0 3/84 (3.57%)  5 0/4 (0.00%)  0
Bronchial wall thickening † 1  0/170 (0.00%)  0 0/1 (0.00%)  0 1/84 (1.19%)  1 1/4 (25.00%)  1
Pneumonitis † 1  5/170 (2.94%)  5 0/1 (0.00%)  0 2/84 (2.38%)  2 1/4 (25.00%)  1
Sneezing † 1  1/170 (0.59%)  1 0/1 (0.00%)  0 0/84 (0.00%)  0 1/4 (25.00%)  1
Upper-airway cough syndrome † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 1/84 (1.19%)  1 1/4 (25.00%)  1
Wheezing † 1  4/170 (2.35%)  4 0/1 (0.00%)  0 1/84 (1.19%)  1 1/4 (25.00%)  2
Skin and subcutaneous tissue disorders         
Pruritus † 1  21/170 (12.35%)  21 0/1 (0.00%)  0 8/84 (9.52%)  10 0/4 (0.00%)  0
Rash † 1  12/170 (7.06%)  14 0/1 (0.00%)  0 14/84 (16.67%)  23 0/4 (0.00%)  0
Rash maculo-papular † 1  3/170 (1.76%)  3 0/1 (0.00%)  0 5/84 (5.95%)  8 0/4 (0.00%)  0
Vascular disorders         
Hot flush † 1  8/170 (4.71%)  8 0/1 (0.00%)  0 6/84 (7.14%)  6 0/4 (0.00%)  0
Lymphoedema † 1  9/170 (5.29%)  10 0/1 (0.00%)  0 4/84 (4.76%)  4 0/4 (0.00%)  0
Hypertension † 1  2/170 (1.18%)  2 0/1 (0.00%)  0 1/84 (1.19%)  3 1/4 (25.00%)  1
1
Term from vocabulary, MedDRA 22.1
†
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 study 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 LLC
ClinicalTrials.gov Identifier: NCT02447003    
Other Study ID Numbers: 3475-086
2015-000294-13 ( EudraCT Number )
152987 ( Registry Identifier: JAPIC )
First Submitted: May 14, 2015
First Posted: May 18, 2015
Results First Submitted: November 18, 2020
Results First Posted: December 16, 2020
Last Update Posted: December 16, 2020