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Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012)

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: NCT01848834
Recruitment Status : Completed
First Posted : May 8, 2013
Results First Posted : June 26, 2017
Last Update Posted : June 28, 2021
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
Conditions Cancer
Solid Tumor
Intervention Biological: Pembrolizumab
Enrollment 297
Recruitment Details  
Pre-assignment Details All allocated participants through end of trial (EOT) analysis cutoff date of 30 June 2020.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Period Title: Overall Study
Started 32 61 33 39 132
Treated 32 60 33 39 132
Completed 13 [1] 13 [1] 9 [1] 13 [1] 38 [1]
Not Completed 19 48 24 26 94
Reason Not Completed
Adverse Event             3             11             3             5             9
Death             2             11             1             8             27
Excluded Medication             5             4             3             6             6
Lost to Follow-up             5             5             3             0             3
Physician Decision             1             3             4             0             11
Protocol Violation             0             0             0             0             1
Sponsor Decision             1             1             0             1             1
Withdrawal by Subject             2             13             10             6             36
[1]
Completed means two-year treatment completed
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion Total
Hide Arm/Group Description Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Total of all reporting groups
Overall Number of Baseline Participants 32 61 33 39 132 297
Hide Baseline Analysis Population Description
The baseline analysis population consisted of all allocated participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 61 participants 33 participants 39 participants 132 participants 297 participants
51.9  (12.1) 61.5  (11.5) 68.5  (10.3) 58.3  (13.2) 58.9  (9.7) 59.7  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 61 participants 33 participants 39 participants 132 participants 297 participants
Female
32
 100.0%
12
  19.7%
10
  30.3%
11
  28.2%
22
  16.7%
87
  29.3%
Male
0
   0.0%
49
  80.3%
23
  69.7%
28
  71.8%
110
  83.3%
210
  70.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 61 participants 33 participants 39 participants 132 participants 297 participants
Hispanic or Latino
2
   6.3%
1
   1.6%
1
   3.0%
1
   2.6%
7
   5.3%
12
   4.0%
Not Hispanic or Latino
29
  90.6%
58
  95.1%
23
  69.7%
37
  94.9%
108
  81.8%
255
  85.9%
Unknown or Not Reported
1
   3.1%
2
   3.3%
9
  27.3%
1
   2.6%
17
  12.9%
30
  10.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 61 participants 33 participants 39 participants 132 participants 297 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.6%
1
   0.8%
2
   0.7%
Asian
0
   0.0%
1
   1.6%
0
   0.0%
19
  48.7%
28
  21.2%
48
  16.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  21.9%
6
   9.8%
2
   6.1%
0
   0.0%
4
   3.0%
19
   6.4%
White
25
  78.1%
53
  86.9%
31
  93.9%
19
  48.7%
95
  72.0%
223
  75.1%
More than one race
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
1
   0.8%
2
   0.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   2.3%
3
   1.0%
1.Primary Outcome
Title Number of Participants Experiencing Adverse Events (AEs)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course pembrolizumab treatment per protocol.
Time Frame Serious AEs: Up to 90 days after last dose of treatment (Up to 28 months); nonserious AEs: Up to 30 days after last dose of treatment (Up to 26 months) - through final analysis (FA) cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 32 60 33 39 132
Measure Type: Count of Participants
Unit of Measure: Participants
32
 100.0%
58
  96.7%
33
 100.0%
39
 100.0%
130
  98.5%
2.Primary Outcome
Title Number of Participants Discontinuing From Study Treatment Due to an AE
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Some cases of clinical progression that led to discontinuation of study treatment were captured as AEs that led to discontinuation of study treatment. The number of participants who discontinued study treatment due to an AE was presented for the first course pembrolizumab treatment per protocol.
Time Frame Up to last dose of study treatment (Up to approximately 25 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, B2, D) & 01 Sep 2015 (Cohort C)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 32 60 33 39 132
Measure Type: Count of Participants
Unit of Measure: Participants
6
  18.8%
12
  20.0%
8
  24.2%
2
   5.1%
21
  15.9%
3.Primary Outcome
Title Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Response Rate Based on Blinded Independent Central Radiology (BICR) Review (Cohorts A, B, C, and D)
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants who experienced 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) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR for Cohorts A, B, C and D participants was presented for the first course of pembrolizumab treatment per protocol. Cohorts A, B, C and D enrolled participants with programmed cell death-ligand 1 (PD-L1) positive tumors.
Time Frame Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of Cohorts A, B, C and D participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 32 60 33 39
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
15.6
(5.3 to 32.8)
16.7
(8.3 to 28.5)
21.2
(9.0 to 38.9)
20.5
(9.3 to 36.5)
4.Primary Outcome
Title Overall RECIST 1.1 Response Rate Based on BICR Review for Participants in Cohort B2
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 was presented for the first course of pembrolizumab treatment per protocol.
Time Frame Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort B2 participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description:
Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 132
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
18.2
(12.0 to 25.8)
5.Secondary Outcome
Title Overall RECIST 1.1 Response Rate Based on BICR Review, Cohorts B and B2 Human Papilloma Virus (HPV)-Positive Participants
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who had tumors which were HPV positive and who experienced a CR or PR in the combined Cohorts B2 and B2 was presented for the first course of pembrolizumab treatment per protocol.
Time Frame Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort B and Cohort B2 HPV-positive participants who received ≥1 dose of study treatment.
Arm/Group Title Cohorts B & B2: Head & Neck Cancer HPV-Positive Participants
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks or pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
21.9
(12.5 to 34.0)
6.Secondary Outcome
Title Overall RECIST 1.1 Response Rate Based on BICR Review, Cohort D Asia-Pacific (AP) Participants
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were from the Asia Pacific region and experienced a CR or PR in Cohort D was presented for the first course of pembrolizumab treatment per protocol.
Time Frame Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort D participants from AP region who received ≥1 dose of study treatment.
Arm/Group Title Cohort D: Gastric Cancer AP Participants
Hide Arm/Group Description:
Participants who were from the Asia Pacific region received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
21.1
(6.1 to 45.6)
7.Secondary Outcome
Title Overall RECIST 1.1 Response Rate Based on BICR Review, for Participants Previously Treated With Cetuximab and Platinum in Cohorts B and B2
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The percentage of participants who were previously treated with cetuximab and platinum and experienced a CR or PR in the Cohorts B and B2 was presented for the first course of pembrolizumab treatment per protocol.
Time Frame Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort B or B2 participants who progressed following cetuximab and platinum therapy and received ≥1 dose of study treatment.
Arm/Group Title Cohorts B & B2: Head & Neck Cancer
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks (Cohort B) or pembrolizumab, 200 mg, IV once every 3 weeks (Cohort B2), and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
14.5
(8.5 to 22.5)
8.Secondary Outcome
Title Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohorts A, B, C and D
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohorts A, B, C and D based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for Cohort B2 in a separate outcome measure.
Time Frame Every 8 weeks until disease progression (Cohorts A, B, D: Up to ~ 35 months; Cohort C: Up to ~ 28 months) - through FA cutoff date 26 Apr 2016 (Cohorts: A, B, D) & 01 Sep 2015 (Cohort C)
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort A, B, C and D participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 32 60 33 39
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
15.6
(5.3 to 32.8)
16.7
(8.3 to 28.5)
21.2
(9.0 to 38.9)
33.3
(19.1 to 50.2)
9.Secondary Outcome
Title Overall RECIST 1.1 Response Rate Based on Investigator Assessment for Cohort B2
Hide Description ORR was defined as the percentage of participants in the analysis population who experienced a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) and was assessed by Investigator evaluation. The percentage of participants who experienced a CR or PR in Cohort B2 based on investigator assessment was presented for the first course of pembrolizumab treatment per protocol. ORR per RECIST 1.1 based on investigator assessment was presented for the other cohorts in a separate outcome measure.
Time Frame Every 8 weeks until disease progression (Up to ~ 35 months) - through FA cutoff date 26 Apr 2016
Hide Outcome Measure Data
Hide Analysis Population Description
The population consisted of all Cohort B2 participants who received ≥1 dose of study treatment.
Arm/Group Title Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description:
Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 132
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
20.5
(13.9 to 28.3)
10.Other Pre-specified Outcome
Title Number of Participants With Log Fold Change From Baseline in Cytokines (Interleukin 10 [IL-10]) >1
Hide Description IL-10 is an anti-inflammatory cytokine. The number of participants with a log fold change from Baseline in IL-10 >1 was to be presented. Protocol Amendment 03 (26 May 2015) removed the secondary objective of investigating the relationship between programmed cell death 1 (PD-1) inhibition and up-regulation of cytokines biomarkers predicting response (e.g. IL-10) from the protocol. No data were collected for this outcome measure.
Time Frame Baseline and Week 8
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Hide Analysis Population Description
The population was to consist of all allocated participants who: 1) received ≥1 dose of study treatment and 2) had a baseline IL-10 assessment, and 3) had a post baseline IL-10 assessment. No data were collected for this outcome measure.
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description:
Participants received pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Serious and non-serious AEs were collected up to ~ 71 months and all-cause mortality up to ~ 85 months for pembrolizumab first and second course treatment (through end of trial (EOT) cutoff date 30 June 2020).
Adverse Event Reporting Description All-cause mortality was reported on all allocated participants (first and second course). Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. MedDRA preferred terms 'Progressive Disease' and 'Malignant Neoplasm Progression' not related to the drug were excluded.
 
Arm/Group Title Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Hide Arm/Group Description Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 10 mg/kg, IV once every 2 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression. Participants received pembrolizumab, 200 mg, IV once every 3 weeks, and continued to receive study drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years). Participants who stopped study treatment without progression (e.g. completed 2 years) may have been eligible for up to 1 year of retreatment upon subsequently experiencing disease progression.
All-Cause Mortality
Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/32 (78.13%)      54/61 (88.52%)      29/33 (87.88%)      34/39 (87.18%)      110/132 (83.33%)    
Hide Serious Adverse Events
Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/32 (40.63%)      27/60 (45.00%)      21/33 (63.64%)      17/39 (43.59%)      60/132 (45.45%)    
Blood and lymphatic system disorders           
Anaemia  1  1/32 (3.13%)  1 2/60 (3.33%)  2 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Anaemia of malignant disease  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Disseminated intravascular coagulation  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Febrile neutropenia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Immune thrombocytopenia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Neutropenia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Cardiac disorders           
Atrial fibrillation  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Cardiac arrest  1  0/32 (0.00%)  0 2/60 (3.33%)  2 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Cardiac failure congestive  1  0/32 (0.00%)  0 2/60 (3.33%)  3 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Myocardial infarction  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Pericardial effusion  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Endocrine disorders           
Hypercalcaemia of malignancy  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  2
Eye disorders           
Vision blurred  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Gastrointestinal disorders           
Abdominal pain  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 2/39 (5.13%)  2 1/132 (0.76%)  1
Autoimmune colitis  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Coeliac disease  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Colitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  2
Constipation  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Diarrhoea  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  1
Gastric ulcer  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Gastrointestinal haemorrhage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Intestinal obstruction  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Large intestine perforation  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Lip swelling  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Mouth haemorrhage  1  0/32 (0.00%)  0 1/60 (1.67%)  2 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  2
Nausea  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Oesophageal perforation  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Oesophageal stenosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  2 0/132 (0.00%)  0
Oesophagitis  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Small intestinal obstruction  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  2 0/39 (0.00%)  0 0/132 (0.00%)  0
Stomatitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Tongue oedema  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Upper gastrointestinal haemorrhage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 2/39 (5.13%)  3 1/132 (0.76%)  1
Vomiting  1  0/32 (0.00%)  0 2/60 (3.33%)  2 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  2
General disorders           
Death  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 4/132 (3.03%)  4
Face oedema  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Fatigue  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Localised oedema  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 2/132 (1.52%)  2
Malaise  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Oedema peripheral  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Pyrexia  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Swelling face  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 2/132 (1.52%)  2
Hepatobiliary disorders           
Cholangitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Cholangitis acute  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Hepatitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Hyperbilirubinaemia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Infections and infestations           
Abscess neck  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Biliary tract infection  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Bronchitis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Cellulitis  1  0/32 (0.00%)  0 3/60 (5.00%)  3 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Clostridium difficile colitis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Diverticulitis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Fascial infection  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Infection  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Meningitis aseptic  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Otitis media  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Otitis media bacterial  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Pneumonia  1  0/32 (0.00%)  0 5/60 (8.33%)  8 1/33 (3.03%)  1 1/39 (2.56%)  1 3/132 (2.27%)  4
Pneumonia influenzal  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Sepsis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 2/33 (6.06%)  2 0/39 (0.00%)  0 1/132 (0.76%)  1
Sinusitis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Staphylococcal bacteraemia  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Stoma site infection  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 3/132 (2.27%)  3
Streptococcal bacteraemia  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Urinary tract infection  1  0/32 (0.00%)  0 1/60 (1.67%)  1 3/33 (9.09%)  4 0/39 (0.00%)  0 0/132 (0.00%)  0
Urosepsis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Vascular device infection  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Injury, poisoning and procedural complications           
Arterial injury  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Head injury  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Osteoradionecrosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Post lumbar puncture syndrome  1  1/32 (3.13%)  2 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Post procedural haemorrhage  1  0/32 (0.00%)  0 2/60 (3.33%)  2 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Spinal compression fracture  1  1/32 (3.13%)  1 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Stomal hernia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Investigations           
Alanine aminotransferase increased  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Aspartate aminotransferase increased  1  1/32 (3.13%)  1 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Blood creatinine increased  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Blood fibrinogen decreased  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Hepatic enzyme increased  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Metabolism and nutrition disorders           
Acidosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Decreased appetite  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Dehydration  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Diabetic ketoacidosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Hypercalcaemia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 2/132 (1.52%)  2
Hyperglycaemia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Hyperkalaemia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Hyponatraemia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Back pain  1  2/32 (6.25%)  2 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Fistula discharge  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Musculoskeletal pain  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Myositis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 2/33 (6.06%)  2 0/39 (0.00%)  0 0/132 (0.00%)  0
Neck pain  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Pain in extremity  1  1/32 (3.13%)  1 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Rhabdomyolysis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Spinal osteoarthritis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Spondylitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal cell carcinoma  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Bone cancer metastatic  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Bowen's disease  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Cancer pain  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  1
Diffuse large B-cell lymphoma  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Malignant pleural effusion  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Metastases to bone  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Metastases to peripheral vascular system  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Metastases to rectum  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Squamous cell carcinoma of skin  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Tumour haemorrhage  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 2/132 (1.52%)  2
Nervous system disorders           
Brain oedema  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Carotid artery stenosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Cerebrospinal fluid leakage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Cerebrovascular accident  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Depressed level of consciousness  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Drug withdrawal convulsions  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Encephalopathy  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  1
Headache  1  2/32 (6.25%)  2 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Lacunar infarction  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Neuralgia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Neuromyopathy  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Seizure  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Subarachnoid haemorrhage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  1
Syncope  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 3/132 (2.27%)  3
Toxic encephalopathy  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Product Issues           
Device dislocation  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Device malfunction  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Psychiatric disorders           
Agitation  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Confusional state  1  0/32 (0.00%)  0 2/60 (3.33%)  2 0/33 (0.00%)  0 0/39 (0.00%)  0 3/132 (2.27%)  3
Mental status changes  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Renal and urinary disorders           
Acute kidney injury  1  1/32 (3.13%)  1 0/60 (0.00%)  0 1/33 (3.03%)  2 0/39 (0.00%)  0 0/132 (0.00%)  0
Reproductive system and breast disorders           
Female genital tract fistula  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Acute respiratory distress syndrome  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Apnoea  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Aspiration  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Cough  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Dyspnoea  1  1/32 (3.13%)  1 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 5/132 (3.79%)  5
Haemoptysis  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Hypoxia  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Interstitial lung disease  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 1/132 (0.76%)  1
Organising pneumonia  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Pleural effusion  1  1/32 (3.13%)  1 2/60 (3.33%)  2 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  2
Pneumonia aspiration  1  0/32 (0.00%)  0 2/60 (3.33%)  2 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  3
Pneumonitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  2
Pneumothorax  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Pulmonary embolism  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  2
Pulmonary oedema  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Respiratory disorder  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Respiratory distress  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 3/132 (2.27%)  3
Respiratory failure  1  0/32 (0.00%)  0 4/60 (6.67%)  4 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Tracheomalacia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Upper airway obstruction  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Skin and subcutaneous tissue disorders           
Pemphigoid  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  1 0/132 (0.00%)  0
Rash macular  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 0/39 (0.00%)  0 0/132 (0.00%)  0
Skin haemorrhage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Stasis dermatitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Vascular disorders           
Deep vein thrombosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 1/132 (0.76%)  1
Embolism  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
Haemorrhage  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 1/132 (0.76%)  1
Hypotension  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 0/132 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: Triple Negative Breast Cancer Cohort B: Head & Neck Cancer Cohort C: Urothelial Cancer Cohort D: Gastric Cancer Cohort B2: Head & Neck Cancer Expansion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/32 (96.88%)      58/60 (96.67%)      32/33 (96.97%)      37/39 (94.87%)      124/132 (93.94%)    
Blood and lymphatic system disorders           
Anaemia  1  3/32 (9.38%)  3 19/60 (31.67%)  22 7/33 (21.21%)  7 4/39 (10.26%)  5 27/132 (20.45%)  32
Lymphopenia  1  1/32 (3.13%)  5 5/60 (8.33%)  6 1/33 (3.03%)  1 1/39 (2.56%)  1 1/132 (0.76%)  1
Neutropenia  1  1/32 (3.13%)  4 0/60 (0.00%)  0 0/33 (0.00%)  0 2/39 (5.13%)  10 0/132 (0.00%)  0
Cardiac disorders           
Tachycardia  1  0/32 (0.00%)  0 1/60 (1.67%)  1 2/33 (6.06%)  2 2/39 (5.13%)  2 5/132 (3.79%)  5
Endocrine disorders           
Hyperthyroidism  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 3/39 (7.69%)  3 0/132 (0.00%)  0
Hypothyroidism  1  1/32 (3.13%)  1 9/60 (15.00%)  10 0/33 (0.00%)  0 5/39 (12.82%)  5 19/132 (14.39%)  20
Gastrointestinal disorders           
Abdominal discomfort  1  1/32 (3.13%)  1 0/60 (0.00%)  0 1/33 (3.03%)  1 4/39 (10.26%)  5 2/132 (1.52%)  3
Abdominal distension  1  3/32 (9.38%)  3 4/60 (6.67%)  4 1/33 (3.03%)  2 3/39 (7.69%)  3 3/132 (2.27%)  4
Abdominal pain  1  2/32 (6.25%)  2 3/60 (5.00%)  3 6/33 (18.18%)  7 13/39 (33.33%)  16 8/132 (6.06%)  8
Abdominal pain upper  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 4/39 (10.26%)  4 3/132 (2.27%)  3
Ascites  1  1/32 (3.13%)  1 0/60 (0.00%)  0 0/33 (0.00%)  0 3/39 (7.69%)  3 1/132 (0.76%)  1
Constipation  1  6/32 (18.75%)  6 15/60 (25.00%)  17 10/33 (30.30%)  11 7/39 (17.95%)  10 21/132 (15.91%)  22
Diarrhoea  1  9/32 (28.13%)  14 13/60 (21.67%)  20 3/33 (9.09%)  3 5/39 (12.82%)  5 14/132 (10.61%)  16
Dry mouth  1  0/32 (0.00%)  0 3/60 (5.00%)  3 2/33 (6.06%)  2 2/39 (5.13%)  2 4/132 (3.03%)  4
Dyspepsia  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 3/39 (7.69%)  3 1/132 (0.76%)  1
Dysphagia  1  0/32 (0.00%)  0 6/60 (10.00%)  7 0/33 (0.00%)  0 1/39 (2.56%)  1 16/132 (12.12%)  16
Eructation  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 2/39 (5.13%)  2 0/132 (0.00%)  0
Flatulence  1  0/32 (0.00%)  0 1/60 (1.67%)  1 2/33 (6.06%)  2 0/39 (0.00%)  0 1/132 (0.76%)  1
Nausea  1  9/32 (28.13%)  13 15/60 (25.00%)  21 9/33 (27.27%)  12 11/39 (28.21%)  11 20/132 (15.15%)  21
Oral pain  1  0/32 (0.00%)  0 5/60 (8.33%)  5 0/33 (0.00%)  0 0/39 (0.00%)  0 7/132 (5.30%)  7
Stomatitis  1  1/32 (3.13%)  1 3/60 (5.00%)  3 1/33 (3.03%)  1 2/39 (5.13%)  2 6/132 (4.55%)  11
Vomiting  1  6/32 (18.75%)  9 12/60 (20.00%)  13 6/33 (18.18%)  8 9/39 (23.08%)  10 13/132 (9.85%)  14
General disorders           
Asthenia  1  1/32 (3.13%)  1 4/60 (6.67%)  4 2/33 (6.06%)  2 3/39 (7.69%)  3 5/132 (3.79%)  5
Chest pain  1  1/32 (3.13%)  1 2/60 (3.33%)  3 1/33 (3.03%)  1 0/39 (0.00%)  0 9/132 (6.82%)  9
Chills  1  1/32 (3.13%)  1 5/60 (8.33%)  6 3/33 (9.09%)  4 2/39 (5.13%)  2 10/132 (7.58%)  11
Face oedema  1  0/32 (0.00%)  0 4/60 (6.67%)  4 2/33 (6.06%)  2 0/39 (0.00%)  0 1/132 (0.76%)  1
Fatigue  1  17/32 (53.13%)  21 32/60 (53.33%)  35 17/33 (51.52%)  19 12/39 (30.77%)  15 59/132 (44.70%)  64
Malaise  1  0/32 (0.00%)  0 1/60 (1.67%)  1 2/33 (6.06%)  2 1/39 (2.56%)  1 2/132 (1.52%)  2
Oedema peripheral  1  2/32 (6.25%)  2 7/60 (11.67%)  7 11/33 (33.33%)  14 4/39 (10.26%)  4 7/132 (5.30%)  8
Pain  1  2/32 (6.25%)  2 4/60 (6.67%)  4 3/33 (9.09%)  3 0/39 (0.00%)  0 5/132 (3.79%)  5
Pyrexia  1  3/32 (9.38%)  5 12/60 (20.00%)  15 9/33 (27.27%)  11 4/39 (10.26%)  6 22/132 (16.67%)  25
Swelling face  1  0/32 (0.00%)  0 4/60 (6.67%)  5 0/33 (0.00%)  0 0/39 (0.00%)  0 8/132 (6.06%)  8
Temperature intolerance  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 2/39 (5.13%)  2 2/132 (1.52%)  2
Infections and infestations           
Candida infection  1  1/32 (3.13%)  1 2/60 (3.33%)  6 2/33 (6.06%)  2 0/39 (0.00%)  0 4/132 (3.03%)  6
Gingivitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 2/39 (5.13%)  2 1/132 (0.76%)  1
Nasopharyngitis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 1/39 (2.56%)  2 7/132 (5.30%)  9
Pneumonia  1  1/32 (3.13%)  1 4/60 (6.67%)  4 0/33 (0.00%)  0 2/39 (5.13%)  2 8/132 (6.06%)  8
Sinusitis  1  0/32 (0.00%)  0 4/60 (6.67%)  6 3/33 (9.09%)  3 0/39 (0.00%)  0 3/132 (2.27%)  5
Skin infection  1  0/32 (0.00%)  0 4/60 (6.67%)  4 2/33 (6.06%)  2 0/39 (0.00%)  0 5/132 (3.79%)  5
Upper respiratory tract infection  1  3/32 (9.38%)  5 3/60 (5.00%)  4 2/33 (6.06%)  3 2/39 (5.13%)  2 7/132 (5.30%)  10
Urinary tract infection  1  0/32 (0.00%)  0 3/60 (5.00%)  3 6/33 (18.18%)  8 2/39 (5.13%)  3 2/132 (1.52%)  2
Injury, poisoning and procedural complications           
Fall  1  4/32 (12.50%)  4 2/60 (3.33%)  3 0/33 (0.00%)  0 2/39 (5.13%)  2 3/132 (2.27%)  3
Investigations           
Alanine aminotransferase increased  1  4/32 (12.50%)  4 2/60 (3.33%)  3 3/33 (9.09%)  3 4/39 (10.26%)  4 6/132 (4.55%)  7
Amylase increased  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 2/39 (5.13%)  2 0/132 (0.00%)  0
Aspartate aminotransferase increased  1  5/32 (15.63%)  5 2/60 (3.33%)  3 4/33 (12.12%)  4 5/39 (12.82%)  5 8/132 (6.06%)  10
Blood alkaline phosphatase increased  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 4/39 (10.26%)  4 5/132 (3.79%)  6
Blood bilirubin increased  1  1/32 (3.13%)  1 1/60 (1.67%)  1 0/33 (0.00%)  0 2/39 (5.13%)  3 1/132 (0.76%)  1
Blood creatinine increased  1  1/32 (3.13%)  1 4/60 (6.67%)  4 9/33 (27.27%)  10 2/39 (5.13%)  3 4/132 (3.03%)  4
Lymphocyte count decreased  1  0/32 (0.00%)  0 0/60 (0.00%)  0 0/33 (0.00%)  0 0/39 (0.00%)  0 8/132 (6.06%)  9
Platelet count decreased  1  0/32 (0.00%)  0 0/60 (0.00%)  0 3/33 (9.09%)  3 0/39 (0.00%)  0 2/132 (1.52%)  2
Weight decreased  1  1/32 (3.13%)  1 10/60 (16.67%)  10 3/33 (9.09%)  3 6/39 (15.38%)  7 25/132 (18.94%)  32
Weight increased  1  0/32 (0.00%)  0 2/60 (3.33%)  3 3/33 (9.09%)  4 0/39 (0.00%)  0 5/132 (3.79%)  5
Metabolism and nutrition disorders           
Decreased appetite  1  2/32 (6.25%)  2 14/60 (23.33%)  14 13/33 (39.39%)  13 12/39 (30.77%)  13 30/132 (22.73%)  31
Dehydration  1  0/32 (0.00%)  0 6/60 (10.00%)  8 3/33 (9.09%)  3 0/39 (0.00%)  0 9/132 (6.82%)  10
Hypercalcaemia  1  0/32 (0.00%)  0 7/60 (11.67%)  8 0/33 (0.00%)  0 0/39 (0.00%)  0 8/132 (6.06%)  9
Hyperglycaemia  1  0/32 (0.00%)  0 7/60 (11.67%)  11 0/33 (0.00%)  0 2/39 (5.13%)  2 6/132 (4.55%)  6
Hyperkalaemia  1  1/32 (3.13%)  1 5/60 (8.33%)  8 2/33 (6.06%)  2 1/39 (2.56%)  1 3/132 (2.27%)  5
Hypoalbuminaemia  1  1/32 (3.13%)  1 4/60 (6.67%)  4 1/33 (3.03%)  1 1/39 (2.56%)  1 8/132 (6.06%)  8
Hypocalcaemia  1  2/32 (6.25%)  2 4/60 (6.67%)  4 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  2
Hypoglycaemia  1  0/32 (0.00%)  0 4/60 (6.67%)  6 0/33 (0.00%)  0 1/39 (2.56%)  1 1/132 (0.76%)  1
Hypokalaemia  1  1/32 (3.13%)  1 11/60 (18.33%)  25 3/33 (9.09%)  3 2/39 (5.13%)  2 10/132 (7.58%)  11
Hypomagnesaemia  1  0/32 (0.00%)  0 5/60 (8.33%)  5 2/33 (6.06%)  3 3/39 (7.69%)  3 8/132 (6.06%)  9
Hyponatraemia  1  2/32 (6.25%)  2 10/60 (16.67%)  18 5/33 (15.15%)  12 2/39 (5.13%)  2 12/132 (9.09%)  13
Hypophosphataemia  1  2/32 (6.25%)  2 6/60 (10.00%)  8 2/33 (6.06%)  4 0/39 (0.00%)  0 7/132 (5.30%)  12
Musculoskeletal and connective tissue disorders           
Arthralgia  1  8/32 (25.00%)  12 11/60 (18.33%)  13 3/33 (9.09%)  3 6/39 (15.38%)  6 16/132 (12.12%)  21
Back pain  1  6/32 (18.75%)  6 9/60 (15.00%)  10 6/33 (18.18%)  7 4/39 (10.26%)  4 13/132 (9.85%)  13
Flank pain  1  0/32 (0.00%)  0 0/60 (0.00%)  0 2/33 (6.06%)  3 2/39 (5.13%)  2 0/132 (0.00%)  0
Groin pain  1  0/32 (0.00%)  0 0/60 (0.00%)  0 4/33 (12.12%)  4 0/39 (0.00%)  0 0/132 (0.00%)  0
Muscle spasms  1  1/32 (3.13%)  1 2/60 (3.33%)  3 3/33 (9.09%)  3 2/39 (5.13%)  2 3/132 (2.27%)  4
Muscular weakness  1  2/32 (6.25%)  2 2/60 (3.33%)  2 1/33 (3.03%)  1 2/39 (5.13%)  2 1/132 (0.76%)  2
Musculoskeletal chest pain  1  7/32 (21.88%)  7 7/60 (11.67%)  8 0/33 (0.00%)  0 0/39 (0.00%)  0 3/132 (2.27%)  3
Musculoskeletal pain  1  2/32 (6.25%)  2 5/60 (8.33%)  6 2/33 (6.06%)  2 3/39 (7.69%)  3 7/132 (5.30%)  7
Myalgia  1  10/32 (31.25%)  12 8/60 (13.33%)  8 3/33 (9.09%)  4 3/39 (7.69%)  3 7/132 (5.30%)  8
Neck pain  1  1/32 (3.13%)  1 4/60 (6.67%)  4 0/33 (0.00%)  0 1/39 (2.56%)  1 13/132 (9.85%)  13
Pain in extremity  1  4/32 (12.50%)  5 2/60 (3.33%)  2 3/33 (9.09%)  3 1/39 (2.56%)  1 6/132 (4.55%)  8
Pain in jaw  1  0/32 (0.00%)  0 3/60 (5.00%)  4 2/33 (6.06%)  2 1/39 (2.56%)  1 1/132 (0.76%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain  1  2/32 (6.25%)  2 0/60 (0.00%)  0 1/33 (3.03%)  1 1/39 (2.56%)  1 2/132 (1.52%)  2
Nervous system disorders           
Balance disorder  1  2/32 (6.25%)  2 1/60 (1.67%)  1 1/33 (3.03%)  1 0/39 (0.00%)  0 2/132 (1.52%)  2
Depressed level of consciousness  1  0/32 (0.00%)  0 0/60 (0.00%)  0 2/33 (6.06%)  2 0/39 (0.00%)  0 0/132 (0.00%)  0
Dizziness  1  3/32 (9.38%)  4 10/60 (16.67%)  11 2/33 (6.06%)  2 4/39 (10.26%)  4 7/132 (5.30%)  7
Headache  1  3/32 (9.38%)  5 10/60 (16.67%)  12 2/33 (6.06%)  2 3/39 (7.69%)  3 13/132 (9.85%)  15
Peripheral sensory neuropathy  1  0/32 (0.00%)  0 1/60 (1.67%)  1 1/33 (3.03%)  1 3/39 (7.69%)  3 3/132 (2.27%)  3
Psychiatric disorders           
Anxiety  1  1/32 (3.13%)  1 6/60 (10.00%)  7 1/33 (3.03%)  1 0/39 (0.00%)  0 5/132 (3.79%)  5
Confusional state  1  1/32 (3.13%)  1 3/60 (5.00%)  3 4/33 (12.12%)  4 0/39 (0.00%)  0 2/132 (1.52%)  2
Depression  1  0/32 (0.00%)  0 2/60 (3.33%)  2 2/33 (6.06%)  2 1/39 (2.56%)  1 6/132 (4.55%)  6
Insomnia  1  2/32 (6.25%)  2 5/60 (8.33%)  6 0/33 (0.00%)  0 1/39 (2.56%)  1 9/132 (6.82%)  9
Restlessness  1  0/32 (0.00%)  0 0/60 (0.00%)  0 3/33 (9.09%)  3 0/39 (0.00%)  0 0/132 (0.00%)  0
Renal and urinary disorders           
Haematuria  1  0/32 (0.00%)  0 0/60 (0.00%)  0 3/33 (9.09%)  3 0/39 (0.00%)  0 0/132 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough  1  5/32 (15.63%)  7 9/60 (15.00%)  10 3/33 (9.09%)  4 8/39 (20.51%)  9 21/132 (15.91%)  24
Dyspnoea  1  7/32 (21.88%)  9 13/60 (21.67%)  15 7/33 (21.21%)  7 1/39 (2.56%)  1 21/132 (15.91%)  21
Dyspnoea exertional  1  0/32 (0.00%)  0 1/60 (1.67%)  1 2/33 (6.06%)  2 0/39 (0.00%)  0 3/132 (2.27%)  3
Oropharyngeal pain  1  0/32 (0.00%)  0 6/60 (10.00%)  10 1/33 (3.03%)  1 3/39 (7.69%)  3 4/132 (3.03%)  5
Pleural effusion  1  4/32 (12.50%)  5 2/60 (3.33%)  2 2/33 (6.06%)  2 0/39 (0.00%)  0 3/132 (2.27%)  3
Productive cough  1  1/32 (3.13%)  1 6/60 (10.00%)  7 0/33 (0.00%)  0 1/39 (2.56%)  1 6/132 (4.55%)  6
Wheezing  1  0/32 (0.00%)  0 3/60 (5.00%)  4 0/33 (0.00%)  0 2/39 (5.13%)  2 2/132 (1.52%)  3
Skin and subcutaneous tissue disorders           
Alopecia  1  3/32 (9.38%)  3 1/60 (1.67%)  1 2/33 (6.06%)  2 0/39 (0.00%)  0 0/132 (0.00%)  0
Dry skin  1  2/32 (6.25%)  2 2/60 (3.33%)  2 1/33 (3.03%)  1 0/39 (0.00%)  0 12/132 (9.09%)  14
Erythema  1  2/32 (6.25%)  3 1/60 (1.67%)  1 0/33 (0.00%)  0 1/39 (2.56%)  1 2/132 (1.52%)  3
Hyperhidrosis  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 3/39 (7.69%)  3 2/132 (1.52%)  2
Night sweats  1  1/32 (3.13%)  1 2/60 (3.33%)  2 0/33 (0.00%)  0 2/39 (5.13%)  2 6/132 (4.55%)  6
Pruritus  1  4/32 (12.50%)  5 8/60 (13.33%)  13 3/33 (9.09%)  4 6/39 (15.38%)  7 14/132 (10.61%)  15
Rash  1  4/32 (12.50%)  6 11/60 (18.33%)  13 2/33 (6.06%)  2 2/39 (5.13%)  3 18/132 (13.64%)  22
Rash maculo-papular  1  0/32 (0.00%)  0 0/60 (0.00%)  0 1/33 (3.03%)  1 0/39 (0.00%)  0 7/132 (5.30%)  9
Urticaria  1  0/32 (0.00%)  0 1/60 (1.67%)  1 0/33 (0.00%)  0 2/39 (5.13%)  2 2/132 (1.52%)  2
Vascular disorders           
Hypotension  1  1/32 (3.13%)  1 10/60 (16.67%)  11 3/33 (9.09%)  3 1/39 (2.56%)  1 7/132 (5.30%)  7
1
Term from vocabulary, MedDRA 23.0
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.
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 of Results:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT01848834    
Other Study ID Numbers: 3475-012
2012-005771-14 ( EudraCT Number )
142453 ( Registry Identifier: JAPIC_CTI )
MK-3475-012 ( Other Identifier: Merck )
First Submitted: May 3, 2013
First Posted: May 8, 2013
Results First Submitted: April 7, 2017
Results First Posted: June 26, 2017
Last Update Posted: June 28, 2021