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A Safety Trial of Nivolumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Chemotherapy Regimen (CheckMate153)

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: NCT02066636
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : October 27, 2022
Last Update Posted : October 27, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Small Cell Lung Cancer (NSCLC)
Intervention Drug: Nivolumab
Enrollment 1428
Recruitment Details  
Pre-assignment Details After 1 year of treatment, participants who are still on treatment are randomized to Cohort A or Cohort B.
Arm/Group Title Cohort A: Nivolumab Monotherapy Cohort B: Nivolumab Monotherapy Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will continue to receive treatment until disease progression, unacceptable toxicity, or withdrawal of informed consent. Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will discontinue treatment. Upon progression, participants can receive retreatment. Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Period Title: Overall Study
Started 127 125 1176
Completed 0 0 0
Not Completed 127 125 1176
Reason Not Completed
Disease progression             51             60             700
Study drug toxicity             13             2             58
Death             4             2             158
Adverse event unrelated to study drug             6             4             45
Participant request to discontinue treatment             12             12             70
Participant withdrew consent             10             18             61
Lost to Follow-up             0             2             2
Maximum clinical benefit             2             2             3
Poor/non-compliance             2             1             1
Participant no loner meets study criteria             3             2             28
Administrative reasons by sponsor             8             5             0
Other reasons             16             15             50
Arm/Group Title Cohort A: Nivolumab Monotherapy Cohort B: Nivolumab Monotherapy Nivolumab Monotherapy (Not Randomized) Total
Hide Arm/Group Description Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will continue to receive treatment until disease progression, unacceptable toxicity, or withdrawal of informed consent. Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will discontinue treatment. Upon progression, participants can receive retreatment. Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B). Total of all reporting groups
Overall Number of Baseline Participants 127 125 1176 1428
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 127 participants 125 participants 1176 participants 1428 participants
66.2  (10.27) 66.6  (7.97) 66.1  (9.82) 66.1  (9.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 127 participants 125 participants 1176 participants 1428 participants
Female
67
  52.8%
62
  49.6%
528
  44.9%
657
  46.0%
Male
60
  47.2%
63
  50.4%
648
  55.1%
771
  54.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 127 participants 125 participants 1176 participants 1428 participants
Hispanic or Latino
3
   2.4%
7
   5.6%
31
   2.6%
41
   2.9%
Not Hispanic or Latino
124
  97.6%
118
  94.4%
1139
  96.9%
1381
  96.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
6
   0.5%
6
   0.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 127 participants 125 participants 1176 participants 1428 participants
American Indian or Alaska Native
0
   0.0%
1
   0.8%
4
   0.3%
5
   0.4%
Asian
3
   2.4%
1
   0.8%
38
   3.2%
42
   2.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
2
   0.2%
2
   0.1%
Black or African American
13
  10.2%
8
   6.4%
84
   7.1%
105
   7.4%
White
111
  87.4%
114
  91.2%
1041
  88.5%
1266
  88.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.8%
7
   0.6%
8
   0.6%
1.Primary Outcome
Title The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5)
Hide Description A treatment related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that has a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants prior to randomization and treated participants randomized to Cohort A and B
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
All Participants that received nivolumab administered intravenously at 3 mg/kg every two weeks for up to 1 year.
Overall Number of Participants Analyzed 127 125 1428
Measure Type: Count of Participants
Unit of Measure: Participants
Gastrointestinal Adverse Event (Grade3-4)
3
   2.4%
0
   0.0%
20
   1.4%
Gastrointestinal Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
1
   0.1%
Hepatic Adverse Event (Grade3-4)
1
   0.8%
0
   0.0%
19
   1.3%
Hepatic Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Pulmonary Adverse Event (Grade3-4)
1
   0.8%
1
   0.8%
18
   1.3%
Pulmonary Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Renal Adverse Event (Grade3-4)
0
   0.0%
0
   0.0%
4
   0.3%
Renal Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Skin Adverse Event (Grade3-4)
1
   0.8%
1
   0.8%
15
   1.1%
Skin Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Hypersensitivity/Infusion Reaction Events (Grade3-4)
0
   0.0%
0
   0.0%
4
   0.3%
Hypersensitivity/Infusion Reaction Events (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Endocrinopathies (Grade3-4)
0
   0.0%
0
   0.0%
6
   0.4%
Endocrinopathies (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Median Time to Onset of Select Adverse Events (Grade 3-5)
Hide Description The time from first dose to the first occurrence of any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Overall Number of Participants Analyzed 10 4 38
Median (Full Range)
Unit of Measure: Weeks
Endocrine Adverse Event Number Analyzed 3 participants 1 participants 3 participants
12.14
(11.0 to 45.4)
25.3
(25.3 to 25.3)
11.14
(5.6 to 42.7)
Gastrointestinal Adverse Event Number Analyzed 10 participants 4 participants 29 participants
82.71
(22.7 to 272.3)
49.21
(33.9 to 59.4)
17.86
(0.7 to 46.1)
Hepatic Adverse Event Number Analyzed 2 participants 0 participants 33 participants
84.50
(16.4 to 152.6)
4.14
(1.3 to 42.1)
Pulmonary Adverse Event Number Analyzed 2 participants 0 participants 38 participants
156.21
(97.9 to 214.6)
7.79
(0.6 to 35.9)
Renal Adverse Event Number Analyzed 2 participants 1 participants 13 participants
108.00
(35.9 to 180.1)
15.1
(15.1 to 15.1)
6.71
(3.0 to 49.6)
Skin Adverse Event Number Analyzed 5 participants 2 participants 11 participants
26.14
(0.1 to 48.1)
18.14
(16.1 to 20.1)
10.57
(2.1 to 51.6)
Hypersensitivity/Infusion Reaction Number Analyzed 0 participants 1 participants 4 participants
42.00
(42.0 to 42.0)
2.36
(2.0 to 8.1)
3.Secondary Outcome
Title Median Time to Resolution of Select Adverse Events (Grade 3-5)
Hide Description The time from the onset of any select adverse event of interest to its resolution or stabilization. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Overall Number of Participants Analyzed 10 4 38
Median (Full Range)
Unit of Measure: Weeks
Endocrine Adverse Event Number Analyzed 3 participants 1 participants 3 participants
3.43
(0.4 to 36.1)
1.00
(1.0 to 1.0)
3.57
(0.9 to 4.4)
Gastrointestinal Adverse Event Number Analyzed 10 participants 4 participants 29 participants
4.79
(0.4 to 29.4)
1.50
(0.3 to 3.0)
1.86
(0.6 to 27.1)
Hepatic Adverse Event Number Analyzed 2 participants 0 participants 33 participants
1.36
(0.4 to 2.3)
12.57
(0.1 to 36.9)
Pulmonary Adverse Event Number Analyzed 2 participants 0 participants 38 participants
1.14
(0.7 to 1.6)
2.57
(0.1 to 30.3)
Renal Adverse Event Number Analyzed 2 participants 1 participants 13 participants
0.64
(0.4 to 0.9)
1.9
(1.9 to 1.9)
1.29
(0.3 to 5.1)
Skin Adverse Event Number Analyzed 5 participants 2 participants 11 participants
2.57
(2.1 to 32.9)
2.43
(2.1 to 2.7)
9.14
(1.0 to 234)
Hypersensitivity/Infusion Reaction Number Analyzed 0 participants 1 participants 4 participants
0.1
(0.1 to 0.1)
0.1
(0.1 to 0.1)
4.Secondary Outcome
Title The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events
Hide Description The number of participants receiving medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Overall Number of Participants Analyzed 40 17 314
Measure Type: Count of Participants
Unit of Measure: Participants
Endocrine Adverse Event Number Analyzed 12 participants 9 participants 209 participants
1
   8.3%
2
  22.2%
15
   7.2%
Gastrointestinal Adverse Event Number Analyzed 40 participants 17 participants 288 participants
5
  12.5%
2
  11.8%
35
  12.2%
Hepatic Adverse Event Number Analyzed 7 participants 6 participants 122 participants
0
   0.0%
0
   0.0%
13
  10.7%
Pulmonary Adverse Event Number Analyzed 12 participants 6 participants 73 participants
11
  91.7%
4
  66.7%
42
  57.5%
Renal Adverse Event Number Analyzed 21 participants 5 participants 96 participants
1
   4.8%
0
   0.0%
12
  12.5%
Skin Adverse Event Number Analyzed 33 participants 16 participants 314 participants
17
  51.5%
8
  50.0%
113
  36.0%
Hypersensitivity/Infusion Reaction Number Analyzed 2 participants 2 participants 33 participants
2
 100.0%
1
  50.0%
14
  42.4%
5.Secondary Outcome
Title The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events
Hide Description The number of participants receiving > 40mg prednisone equivalents for any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Overall Number of Participants Analyzed 40 17 314
Measure Type: Count of Participants
Unit of Measure: Participants
Endocrine Adverse Event Number Analyzed 12 participants 9 participants 209 participants
0
   0.0%
0
   0.0%
5
   2.4%
Gastrointestinal Adverse Event Number Analyzed 40 participants 17 participants 288 participants
3
   7.5%
2
  11.8%
21
   7.3%
Hepatic Adverse Event Number Analyzed 7 participants 6 participants 122 participants
0
   0.0%
0
   0.0%
8
   6.6%
Pulmonary Adverse Event Number Analyzed 12 participants 6 participants 73 participants
7
  58.3%
4
  66.7%
31
  42.5%
Renal Adverse Event Number Analyzed 21 participants 5 participants 96 participants
1
   4.8%
0
   0.0%
10
  10.4%
Skin Adverse Event Number Analyzed 33 participants 16 participants 314 participants
2
   6.1%
2
  12.5%
14
   4.5%
Hypersensitivity/Infusion Reaction Number Analyzed 2 participants 2 participants 33 participants
2
 100.0%
1
  50.0%
3
   9.1%
6.Secondary Outcome
Title The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events
Hide Description The duration of time participants received medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Not Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B).
Overall Number of Participants Analyzed 40 17 314
Median (Full Range)
Unit of Measure: Weeks
Endocrine Adverse Event Number Analyzed 12 participants 9 participants 209 participants
NA [1] 
(NA to NA)
82.57
(2.0 to 163.1)
2.57
(0.1 to 76.0)
Gastrointestinal Adverse Event Number Analyzed 40 participants 17 participants 288 participants
5.43
(2.4 to 8.1)
2.50
(1.6 to 3.4)
3.79
(0.4 to 32.6)
Hepatic Adverse Event Number Analyzed 7 participants 6 participants 122 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
5.0
(0.4 to 14.0)
Pulmonary Adverse Event Number Analyzed 12 participants 6 participants 73 participants
6.57
(0.3 to 27.1)
2.86
(1.1 to 5.9)
3.57
(0.1 to 26.1)
Renal Adverse Event Number Analyzed 21 participants 5 participants 96 participants
0.7
(0.7 to 0.7)
NA [1] 
(NA to NA)
2.57
(0.3 to 16.9)
Skin Adverse Event Number Analyzed 33 participants 16 participants 314 participants
18.14
(0.9 to 151.0)
6.71
(1.0 to 16.4)
4.07
(0.1 to 80.1)
Hypersensitivity/Infusion Reaction Number Analyzed 2 participants 2 participants 33 participants
2.71
(1.0 to 4.4)
2.0
(2.0 to 2.0)
0.14
(0.1 to 2.1)
[1]
Insufficient number of participants with events
7.Secondary Outcome
Title The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time Frame From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants prior to randomization and treated participants randomized to Cohort A and B
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized)
Hide Arm/Group Description:
All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent.
All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment.
All Participants that received nivolumab administered intravenously at 3 mg/kg every two weeks for up to 1 year.
Overall Number of Participants Analyzed 127 125 1428
Measure Type: Count of Participants
Unit of Measure: Participants
Gastrointestinal Adverse Event (Grade3-4)
7
   5.5%
2
   1.6%
35
   2.5%
Gastrointestinal Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
1
   0.1%
Hepatic Adverse Event (Grade3-4)
1
   0.8%
0
   0.0%
34
   2.4%
Hepatic Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Pulmonary Adverse Event (Grade3-4)
2
   1.6%
3
   2.4%
31
   2.2%
Pulmonary Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
7
   0.5%
Renal Adverse Event (Grade3-4)
1
   0.8%
1
   0.8%
14
   1.0%
Renal Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
1
   0.1%
Skin Adverse Event (Grade3-4)
1
   0.8%
2
   1.6%
18
   1.3%
Skin Adverse Event (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Hypersensitivity/Infusion Reaction Events (Grade3-4)
0
   0.0%
0
   0.0%
5
   0.4%
Hypersensitivity/Infusion Reaction Events (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Endocrinopathies (Grade3-4)
0
   0.0%
0
   0.0%
8
   0.6%
Endocrinopathies (Grade 5)
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Participants were assessed for all-cause mortality from their first dose to study completion (up to approximately 90 months) . SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 88 months).
Adverse Event Reporting Description Post-Randomization indicates only data after randomization is summarized (applies to Cohort A and B). Pre-Randomized indicates only data before randomization is summarized (applies to all treated participants). Total indicates data is summarized throughout the full duration of the study (applies to all treated participants).
 
Arm/Group Title Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized) Nivolumab Monotherapy (Total)
Hide Arm/Group Description All participants that continued to receive treatment after completing 1 year (52 weeks) of nivolumab administered intravenously at 3 mg/kg every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent. All participants that discontinued treatment after 1 year (52 weeks) of receiving nivolumab administered intravenously at 3 mg/kg every two weeks. Upon progression, participants can receive retreatment. All Participants that received nivolumab administered intravenously at 3 mg/kg every two weeks for up to 1 year. All Participants that received nivolumab administered intravenously at 3 mg/kg every two weeks regardless of continuation or discontinuation of treatment.
All-Cause Mortality
Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized) Nivolumab Monotherapy (Total)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   63/127 (49.61%)   77/125 (61.60%)   1040/1428 (72.83%)   1180/1428 (82.63%) 
Hide Serious Adverse Events
Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized) Nivolumab Monotherapy (Total)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/127 (44.88%)   52/125 (41.60%)   870/1428 (60.92%)   918/1428 (64.29%) 
Blood and lymphatic system disorders         
Anaemia † 1  0/127 (0.00%)  2/125 (1.60%)  12/1428 (0.84%)  13/1428 (0.91%) 
Coagulopathy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Febrile neutropenia † 1  0/127 (0.00%)  1/125 (0.80%)  7/1428 (0.49%)  7/1428 (0.49%) 
Hypercoagulation † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Leukocytosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Neutropenia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Thrombocytopenia † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Thrombotic thrombocytopenic purpura † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cardiac disorders         
Acute coronary syndrome † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Acute myocardial infarction † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Angina pectoris † 1  0/127 (0.00%)  1/125 (0.80%)  2/1428 (0.14%)  2/1428 (0.14%) 
Angina unstable † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Arrhythmia † 1  0/127 (0.00%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Atrial fibrillation † 1  1/127 (0.79%)  1/125 (0.80%)  12/1428 (0.84%)  14/1428 (0.98%) 
Atrial flutter † 1  1/127 (0.79%)  0/125 (0.00%)  2/1428 (0.14%)  3/1428 (0.21%) 
Atrial thrombosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Atrioventricular block † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cardiac arrest † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  5/1428 (0.35%) 
Cardiac disorder † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cardiac failure † 1  1/127 (0.79%)  0/125 (0.00%)  3/1428 (0.21%)  4/1428 (0.28%) 
Cardiac failure congestive † 1  1/127 (0.79%)  0/125 (0.00%)  9/1428 (0.63%)  10/1428 (0.70%) 
Cardiac tamponade † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cardio-respiratory arrest † 1  1/127 (0.79%)  0/125 (0.00%)  6/1428 (0.42%)  7/1428 (0.49%) 
Cardiogenic shock † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cardiomyopathy † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Coronary artery stenosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Myocardial infarction † 1  0/127 (0.00%)  1/125 (0.80%)  7/1428 (0.49%)  8/1428 (0.56%) 
Palpitations † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Pericardial effusion † 1  1/127 (0.79%)  0/125 (0.00%)  11/1428 (0.77%)  12/1428 (0.84%) 
Pericarditis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Sinus node dysfunction † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Sinus tachycardia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Supraventricular tachycardia † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Tachycardia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Ear and labyrinth disorders         
Vestibular disorder † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Endocrine disorders         
Adrenal insufficiency † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Hypercalcaemia of malignancy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hyperthyroidism † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypothyroidism † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Eye disorders         
Ocular myasthenia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Vision blurred † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Gastrointestinal disorders         
Abdominal distension † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Abdominal pain † 1  0/127 (0.00%)  0/125 (0.00%)  17/1428 (1.19%)  18/1428 (1.26%) 
Colitis † 1  4/127 (3.15%)  0/125 (0.00%)  7/1428 (0.49%)  10/1428 (0.70%) 
Colitis ischaemic † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Constipation † 1  0/127 (0.00%)  0/125 (0.00%)  8/1428 (0.56%)  8/1428 (0.56%) 
Diarrhoea † 1  1/127 (0.79%)  0/125 (0.00%)  13/1428 (0.91%)  14/1428 (0.98%) 
Diverticular perforation † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Duodenal ulcer haemorrhage † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Duodenitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Dyspepsia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Dysphagia † 1  0/127 (0.00%)  0/125 (0.00%)  8/1428 (0.56%)  8/1428 (0.56%) 
Enterocolitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Enterocolonic fistula † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Gastric haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Gastritis † 1  2/127 (1.57%)  0/125 (0.00%)  3/1428 (0.21%)  5/1428 (0.35%) 
Gastrointestinal angiectasia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Gastrointestinal haemorrhage † 1  0/127 (0.00%)  1/125 (0.80%)  6/1428 (0.42%)  6/1428 (0.42%) 
Gastrointestinal perforation † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Gastrooesophageal reflux disease † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Haematemesis † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Haemorrhoidal haemorrhage † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Ileus † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Ileus paralytic † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Immune-mediated enterocolitis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Incarcerated umbilical hernia † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Intestinal obstruction † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  4/1428 (0.28%) 
Intestinal perforation † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Large intestine perforation † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Lower gastrointestinal haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Nausea † 1  1/127 (0.79%)  0/125 (0.00%)  12/1428 (0.84%)  13/1428 (0.91%) 
Odynophagia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Oesophageal fistula † 1  0/127 (0.00%)  1/125 (0.80%)  1/1428 (0.07%)  1/1428 (0.07%) 
Oesophageal haemorrhage † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Oesophageal stenosis † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Oesophagitis † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Pancreatitis acute † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pancreatitis chronic † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Proctalgia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Rectal haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Retroperitoneal haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Small intestinal obstruction † 1  1/127 (0.79%)  1/125 (0.80%)  4/1428 (0.28%)  5/1428 (0.35%) 
Stomatitis † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Volvulus † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Vomiting † 1  1/127 (0.79%)  1/125 (0.80%)  9/1428 (0.63%)  10/1428 (0.70%) 
General disorders         
Asthenia † 1  0/127 (0.00%)  0/125 (0.00%)  8/1428 (0.56%)  8/1428 (0.56%) 
Catheter site injury † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Chest pain † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  4/1428 (0.28%) 
Death † 1  0/127 (0.00%)  0/125 (0.00%)  14/1428 (0.98%)  14/1428 (0.98%) 
Fatigue † 1  0/127 (0.00%)  0/125 (0.00%)  9/1428 (0.63%)  9/1428 (0.63%) 
General physical health deterioration † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Generalised oedema † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Infusion site extravasation † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Localised oedema † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Malaise † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Multiple organ dysfunction syndrome † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Non-cardiac chest pain † 1  0/127 (0.00%)  0/125 (0.00%)  15/1428 (1.05%)  15/1428 (1.05%) 
Oedema peripheral † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Pain † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Physical deconditioning † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pyrexia † 1  1/127 (0.79%)  2/125 (1.60%)  8/1428 (0.56%)  8/1428 (0.56%) 
Sudden death † 1  1/127 (0.79%)  0/125 (0.00%)  2/1428 (0.14%)  3/1428 (0.21%) 
Hepatobiliary disorders         
Autoimmune cholangitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Autoimmune hepatitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Biliary obstruction † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Cholecystitis † 1  0/127 (0.00%)  1/125 (0.80%)  3/1428 (0.21%)  3/1428 (0.21%) 
Cholecystitis acute † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Cholelithiasis † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Drug-induced liver injury † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hepatic failure † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hepatic function abnormal † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hepatitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hepatitis acute † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hepatotoxicity † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Immune system disorders         
Anaphylactic shock † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Drug hypersensitivity † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Infections and infestations         
Abscess intestinal † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Abscess oral † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Appendicitis perforated † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Bacteraemia † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Bacterial sepsis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Bronchiolitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Bronchitis † 1  2/127 (1.57%)  1/125 (0.80%)  4/1428 (0.28%)  6/1428 (0.42%) 
Catheter site cellulitis † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Cellulitis † 1  1/127 (0.79%)  0/125 (0.00%)  3/1428 (0.21%)  4/1428 (0.28%) 
Clostridium difficile colitis † 1  2/127 (1.57%)  0/125 (0.00%)  0/1428 (0.00%)  2/1428 (0.14%) 
Clostridium difficile infection † 1  0/127 (0.00%)  1/125 (0.80%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cryptococcosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  0/1428 (0.00%) 
Cystitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Device related infection † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  2/1428 (0.14%) 
Diverticulitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Empyema † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  1/1428 (0.07%) 
Enterobacter pneumonia † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Enterococcal infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Enterocolitis infectious † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Escherichia sepsis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Gastroenteritis viral † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Groin infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Infective exacerbation of chronic obstructive airways disease † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Influenza † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Large intestine infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Meningitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Osteomyelitis † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Otitis media † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Papilloma viral infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pleural infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumococcal sepsis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonia † 1  17/127 (13.39%)  7/125 (5.60%)  118/1428 (8.26%)  137/1428 (9.59%) 
Pneumonia aspiration † 1  0/127 (0.00%)  1/125 (0.80%)  8/1428 (0.56%)  8/1428 (0.56%) 
Pneumonia bacterial † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Pneumonia haemophilus † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonia mycoplasmal † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonia necrotising † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonia pseudomonal † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonia staphylococcal † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Pneumonia streptococcal † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Postoperative wound infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pseudomonas infection † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Pyelonephritis † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Respiratory tract infection † 1  0/127 (0.00%)  1/125 (0.80%)  3/1428 (0.21%)  3/1428 (0.21%) 
Sepsis † 1  3/127 (2.36%)  2/125 (1.60%)  22/1428 (1.54%)  26/1428 (1.82%) 
Septic shock † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Soft tissue infection † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Upper respiratory tract infection † 1  1/127 (0.79%)  1/125 (0.80%)  3/1428 (0.21%)  4/1428 (0.28%) 
Urinary tract infection † 1  1/127 (0.79%)  0/125 (0.00%)  8/1428 (0.56%)  9/1428 (0.63%) 
Urosepsis † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Vascular device infection † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Vulvovaginal candidiasis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Wound infection staphylococcal † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Injury, poisoning and procedural complications         
Accidental overdose † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Ankle fracture † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  1/1428 (0.07%) 
Compression fracture † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Craniocerebral injury † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Fall † 1  1/127 (0.79%)  0/125 (0.00%)  3/1428 (0.21%)  4/1428 (0.28%) 
Femoral neck fracture † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  4/1428 (0.28%) 
Femur fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Fractured sacrum † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hip fracture † 1  0/127 (0.00%)  1/125 (0.80%)  5/1428 (0.35%)  5/1428 (0.35%) 
Ilium fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Infusion related reaction † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Joint dislocation † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Overdose † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Post-traumatic pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Procedural complication † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Procedural pneumothorax † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Product administration error † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Radiation pneumonitis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Radius fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Rib fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Road traffic accident † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Spinal compression fracture † 1  1/127 (0.79%)  0/125 (0.00%)  3/1428 (0.21%)  4/1428 (0.28%) 
Thoracic vertebral fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Ulna fracture † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Wound dehiscence † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Wrist fracture † 1  0/127 (0.00%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Investigations         
Blood alkaline phosphatase increased † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Blood bilirubin increased † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Brain natriuretic peptide increased † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Influenza A virus test positive † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
International normalised ratio increased † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Staphylococcus test positive † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Troponin I increased † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Troponin increased † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Dehydration † 1  2/127 (1.57%)  0/125 (0.00%)  33/1428 (2.31%)  35/1428 (2.45%) 
Diabetic ketoacidosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  0/1428 (0.00%) 
Failure to thrive † 1  0/127 (0.00%)  1/125 (0.80%)  8/1428 (0.56%)  8/1428 (0.56%) 
Hypercalcaemia † 1  1/127 (0.79%)  0/125 (0.00%)  9/1428 (0.63%)  10/1428 (0.70%) 
Hyperkalaemia † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Hypervolaemia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypoalbuminaemia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypocalcaemia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypoglycaemia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Hypokalaemia † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Hypomagnesaemia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hyponatraemia † 1  2/127 (1.57%)  1/125 (0.80%)  8/1428 (0.56%)  10/1428 (0.70%) 
Hypovolaemia † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Metabolic acidosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  0/127 (0.00%)  1/125 (0.80%)  6/1428 (0.42%)  6/1428 (0.42%) 
Back pain † 1  1/127 (0.79%)  0/125 (0.00%)  11/1428 (0.77%)  12/1428 (0.84%) 
Bone pain † 1  0/127 (0.00%)  0/125 (0.00%)  6/1428 (0.42%)  6/1428 (0.42%) 
Flank pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Groin pain † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Intervertebral disc degeneration † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Intervertebral disc protrusion † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Muscle spasms † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Muscular weakness † 1  1/127 (0.79%)  0/125 (0.00%)  9/1428 (0.63%)  10/1428 (0.70%) 
Musculoskeletal chest pain † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Musculoskeletal pain † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Neck pain † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Osteoarthritis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Pain in extremity † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Pathological fracture † 1  1/127 (0.79%)  0/125 (0.00%)  5/1428 (0.35%)  6/1428 (0.42%) 
Polymyositis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Spinal osteoarthritis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Spinal pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Spinal stenosis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Brain neoplasm malignant † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Breast cancer † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Cancer pain † 1  0/127 (0.00%)  0/125 (0.00%)  7/1428 (0.49%)  7/1428 (0.49%) 
Diffuse large B-cell lymphoma † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Gastric cancer † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Intraductal proliferative breast lesion † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Lung neoplasm malignant † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Malignant melanoma in situ † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Malignant neoplasm progression † 1  11/127 (8.66%)  15/125 (12.00%)  509/1428 (35.64%)  521/1428 (36.48%) 
Malignant pleural effusion † 1  0/127 (0.00%)  0/125 (0.00%)  6/1428 (0.42%)  6/1428 (0.42%) 
Metastases to central nervous system † 1  0/127 (0.00%)  1/125 (0.80%)  9/1428 (0.63%)  10/1428 (0.70%) 
Metastases to meninges † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Metastases to spine † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Myelodysplastic syndrome † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Neoplasm malignant † 1  0/127 (0.00%)  0/125 (0.00%)  6/1428 (0.42%)  6/1428 (0.42%) 
Neoplasm progression † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Neuroendocrine carcinoma † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Non-small cell lung cancer † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Pericardial effusion malignant † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Prostate cancer † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Respiratory papilloma † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Second primary malignancy † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Tumour associated fever † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Tumour pain † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Nervous system disorders         
Amnesia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Aphasia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Brain oedema † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Central nervous system haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cerebellar stroke † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Cerebral haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Cerebral infarction † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cerebrospinal fluid leakage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cerebrovascular accident † 1  1/127 (0.79%)  0/125 (0.00%)  9/1428 (0.63%)  10/1428 (0.70%) 
Cervical radiculopathy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Cognitive disorder † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Depressed level of consciousness † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Dizziness † 1  1/127 (0.79%)  0/125 (0.00%)  2/1428 (0.14%)  3/1428 (0.21%) 
Dyskinesia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Embolic stroke † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Encephalopathy † 1  1/127 (0.79%)  0/125 (0.00%)  2/1428 (0.14%)  3/1428 (0.21%) 
Haemorrhage intracranial † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Headache † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hemiparesis † 1  1/127 (0.79%)  0/125 (0.00%)  2/1428 (0.14%)  3/1428 (0.21%) 
Hepatic encephalopathy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hydrocephalus † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Ischaemic cerebral infarction † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Ischaemic stroke † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Lacunar stroke † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Lethargy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Loss of consciousness † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Metabolic encephalopathy † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Partial seizures † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Presyncope † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Seizure † 1  2/127 (1.57%)  1/125 (0.80%)  12/1428 (0.84%)  14/1428 (0.98%) 
Spinal cord compression † 1  0/127 (0.00%)  0/125 (0.00%)  9/1428 (0.63%)  9/1428 (0.63%) 
Subarachnoid haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Syncope † 1  1/127 (0.79%)  1/125 (0.80%)  9/1428 (0.63%)  11/1428 (0.77%) 
Vocal cord paralysis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Product Issues         
Device malfunction † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Psychiatric disorders         
Completed suicide † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Confusional state † 1  1/127 (0.79%)  1/125 (0.80%)  11/1428 (0.77%)  12/1428 (0.84%) 
Delirium † 1  0/127 (0.00%)  0/125 (0.00%)  3/1428 (0.21%)  3/1428 (0.21%) 
Depression † 1  1/127 (0.79%)  1/125 (0.80%)  0/1428 (0.00%)  1/1428 (0.07%) 
Hallucination † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Mental status changes † 1  0/127 (0.00%)  1/125 (0.80%)  9/1428 (0.63%)  9/1428 (0.63%) 
Psychotic disorder † 1  2/127 (1.57%)  0/125 (0.00%)  0/1428 (0.00%)  2/1428 (0.14%) 
Suicidal ideation † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Suicide attempt † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Renal and urinary disorders         
Acute kidney injury † 1  1/127 (0.79%)  1/125 (0.80%)  15/1428 (1.05%)  15/1428 (1.05%) 
Dysuria † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Haematuria † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  4/1428 (0.28%) 
Hydronephrosis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Renal pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Urinary incontinence † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Urinary retention † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Reproductive system and breast disorders         
Adnexal torsion † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pelvic pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure † 1  0/127 (0.00%)  2/125 (1.60%)  18/1428 (1.26%)  18/1428 (1.26%) 
Aspiration † 1  0/127 (0.00%)  1/125 (0.80%)  3/1428 (0.21%)  3/1428 (0.21%) 
Asthma † 1  0/127 (0.00%)  1/125 (0.80%)  1/1428 (0.07%)  1/1428 (0.07%) 
Bronchial fistula † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Bronchial obstruction † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Bronchopleural fistula † 1  0/127 (0.00%)  2/125 (1.60%)  0/1428 (0.00%)  0/1428 (0.00%) 
Bronchospasm † 1  1/127 (0.79%)  0/125 (0.00%)  1/1428 (0.07%)  2/1428 (0.14%) 
Chronic obstructive pulmonary disease † 1  5/127 (3.94%)  7/125 (5.60%)  27/1428 (1.89%)  31/1428 (2.17%) 
Chronic respiratory failure † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Cough † 1  0/127 (0.00%)  0/125 (0.00%)  5/1428 (0.35%)  5/1428 (0.35%) 
Dysphonia † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Dyspnoea † 1  1/127 (0.79%)  1/125 (0.80%)  91/1428 (6.37%)  92/1428 (6.44%) 
Haemoptysis † 1  0/127 (0.00%)  1/125 (0.80%)  10/1428 (0.70%)  10/1428 (0.70%) 
Hypoxia † 1  1/127 (0.79%)  0/125 (0.00%)  16/1428 (1.12%)  17/1428 (1.19%) 
Laryngeal haemorrhage † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Lung opacity † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pleural effusion † 1  1/127 (0.79%)  2/125 (1.60%)  37/1428 (2.59%)  38/1428 (2.66%) 
Pleuritic pain † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pneumonitis † 1  1/127 (0.79%)  0/125 (0.00%)  23/1428 (1.61%)  24/1428 (1.68%) 
Pneumothorax † 1  0/127 (0.00%)  0/125 (0.00%)  10/1428 (0.70%)  10/1428 (0.70%) 
Pulmonary embolism † 1  2/127 (1.57%)  1/125 (0.80%)  40/1428 (2.80%)  43/1428 (3.01%) 
Pulmonary haemorrhage † 1  0/127 (0.00%)  1/125 (0.80%)  2/1428 (0.14%)  2/1428 (0.14%) 
Pulmonary hypertension † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pulmonary oedema † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Pulmonary sarcoidosis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Respiratory arrest † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Respiratory disorder † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Respiratory distress † 1  1/127 (0.79%)  0/125 (0.00%)  4/1428 (0.28%)  5/1428 (0.35%) 
Respiratory failure † 1  1/127 (0.79%)  1/125 (0.80%)  22/1428 (1.54%)  23/1428 (1.61%) 
Wheezing † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Skin and subcutaneous tissue disorders         
Pemphigoid † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  0/1428 (0.00%) 
Psoriasis † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Rash † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Rash maculo-papular † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Skin lesion † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Vascular disorders         
Aortic stenosis † 1  1/127 (0.79%)  0/125 (0.00%)  0/1428 (0.00%)  1/1428 (0.07%) 
Deep vein thrombosis † 1  1/127 (0.79%)  0/125 (0.00%)  16/1428 (1.12%)  17/1428 (1.19%) 
Embolism † 1  0/127 (0.00%)  1/125 (0.80%)  7/1428 (0.49%)  7/1428 (0.49%) 
Haematoma † 1  0/127 (0.00%)  1/125 (0.80%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypertension † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Hypertensive urgency † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Hypotension † 1  0/127 (0.00%)  0/125 (0.00%)  7/1428 (0.49%)  7/1428 (0.49%) 
Jugular vein thrombosis † 1  0/127 (0.00%)  1/125 (0.80%)  0/1428 (0.00%)  1/1428 (0.07%) 
Peripheral embolism † 1  0/127 (0.00%)  0/125 (0.00%)  2/1428 (0.14%)  2/1428 (0.14%) 
Shock haemorrhagic † 1  0/127 (0.00%)  0/125 (0.00%)  1/1428 (0.07%)  1/1428 (0.07%) 
Superior vena cava syndrome † 1  0/127 (0.00%)  0/125 (0.00%)  4/1428 (0.28%)  4/1428 (0.28%) 
1
Term from vocabulary, MedDRA 24.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: Nivolumab Monotherapy (Post-Randomization) Cohort B: Nivolumab Monotherapy (Post-Randomization) Nivolumab Monotherapy (Pre-Randomized) Nivolumab Monotherapy (Total)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   101/127 (79.53%)   82/125 (65.60%)   1287/1428 (90.13%)   1306/1428 (91.46%) 
Blood and lymphatic system disorders         
Anaemia † 1  11/127 (8.66%)  7/125 (5.60%)  208/1428 (14.57%)  222/1428 (15.55%) 
Endocrine disorders         
Hypothyroidism † 1  8/127 (6.30%)  4/125 (3.20%)  129/1428 (9.03%)  136/1428 (9.52%) 
Gastrointestinal disorders         
Abdominal pain † 1  14/127 (11.02%)  7/125 (5.60%)  117/1428 (8.19%)  133/1428 (9.31%) 
Constipation † 1  9/127 (7.09%)  6/125 (4.80%)  274/1428 (19.19%)  290/1428 (20.31%) 
Diarrhoea † 1  36/127 (28.35%)  17/125 (13.60%)  275/1428 (19.26%)  292/1428 (20.45%) 
Nausea † 1  22/127 (17.32%)  9/125 (7.20%)  332/1428 (23.25%)  352/1428 (24.65%) 
Vomiting † 1  15/127 (11.81%)  5/125 (4.00%)  191/1428 (13.38%)  207/1428 (14.50%) 
General disorders         
Asthenia † 1  5/127 (3.94%)  0/125 (0.00%)  73/1428 (5.11%)  79/1428 (5.53%) 
Fatigue † 1  26/127 (20.47%)  17/125 (13.60%)  516/1428 (36.13%)  544/1428 (38.10%) 
Non-cardiac chest pain † 1  6/127 (4.72%)  3/125 (2.40%)  84/1428 (5.88%)  94/1428 (6.58%) 
Oedema peripheral † 1  13/127 (10.24%)  9/125 (7.20%)  180/1428 (12.61%)  197/1428 (13.80%) 
Pyrexia † 1  16/127 (12.60%)  2/125 (1.60%)  123/1428 (8.61%)  143/1428 (10.01%) 
Infections and infestations         
Bronchitis † 1  14/127 (11.02%)  5/125 (4.00%)  50/1428 (3.50%)  64/1428 (4.48%) 
Pneumonia † 1  15/127 (11.81%)  14/125 (11.20%)  89/1428 (6.23%)  102/1428 (7.14%) 
Sinusitis † 1  8/127 (6.30%)  4/125 (3.20%)  59/1428 (4.13%)  65/1428 (4.55%) 
Upper respiratory tract infection † 1  28/127 (22.05%)  15/125 (12.00%)  128/1428 (8.96%)  153/1428 (10.71%) 
Urinary tract infection † 1  12/127 (9.45%)  11/125 (8.80%)  60/1428 (4.20%)  75/1428 (5.25%) 
Injury, poisoning and procedural complications         
Fall † 1  11/127 (8.66%)  10/125 (8.00%)  54/1428 (3.78%)  65/1428 (4.55%) 
Investigations         
Blood creatinine increased † 1  17/127 (13.39%)  4/125 (3.20%)  65/1428 (4.55%)  76/1428 (5.32%) 
Weight decreased † 1  12/127 (9.45%)  20/125 (16.00%)  182/1428 (12.75%)  192/1428 (13.45%) 
Weight increased † 1  15/127 (11.81%)  4/125 (3.20%)  39/1428 (2.73%)  48/1428 (3.36%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  18/127 (14.17%)  13/125 (10.40%)  313/1428 (21.92%)  336/1428 (23.53%) 
Dehydration † 1  9/127 (7.09%)  3/125 (2.40%)  127/1428 (8.89%)  134/1428 (9.38%) 
Hyperglycaemia † 1  7/127 (5.51%)  4/125 (3.20%)  61/1428 (4.27%)  68/1428 (4.76%) 
Hypokalaemia † 1  16/127 (12.60%)  9/125 (7.20%)  126/1428 (8.82%)  138/1428 (9.66%) 
Hypomagnesaemia † 1  14/127 (11.02%)  8/125 (6.40%)  149/1428 (10.43%)  162/1428 (11.34%) 
Hyponatraemia † 1  5/127 (3.94%)  5/125 (4.00%)  97/1428 (6.79%)  102/1428 (7.14%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  30/127 (23.62%)  18/125 (14.40%)  284/1428 (19.89%)  314/1428 (21.99%) 
Back pain † 1  17/127 (13.39%)  11/125 (8.80%)  189/1428 (13.24%)  211/1428 (14.78%) 
Muscle spasms † 1  11/127 (8.66%)  4/125 (3.20%)  44/1428 (3.08%)  57/1428 (3.99%) 
Muscular weakness † 1  5/127 (3.94%)  8/125 (6.40%)  74/1428 (5.18%)  82/1428 (5.74%) 
Musculoskeletal chest pain † 1  9/127 (7.09%)  2/125 (1.60%)  90/1428 (6.30%)  102/1428 (7.14%) 
Myalgia † 1  8/127 (6.30%)  6/125 (4.80%)  60/1428 (4.20%)  67/1428 (4.69%) 
Neck pain † 1  4/127 (3.15%)  7/125 (5.60%)  44/1428 (3.08%)  50/1428 (3.50%) 
Pain in extremity † 1  12/127 (9.45%)  8/125 (6.40%)  101/1428 (7.07%)  112/1428 (7.84%) 
Nervous system disorders         
Dizziness † 1  17/127 (13.39%)  7/125 (5.60%)  140/1428 (9.80%)  156/1428 (10.92%) 
Headache † 1  17/127 (13.39%)  8/125 (6.40%)  140/1428 (9.80%)  161/1428 (11.27%) 
Psychiatric disorders         
Anxiety † 1  7/127 (5.51%)  3/125 (2.40%)  96/1428 (6.72%)  106/1428 (7.42%) 
Depression † 1  3/127 (2.36%)  5/125 (4.00%)  71/1428 (4.97%)  75/1428 (5.25%) 
Insomnia † 1  15/127 (11.81%)  7/125 (5.60%)  128/1428 (8.96%)  147/1428 (10.29%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease † 1  12/127 (9.45%)  9/125 (7.20%)  41/1428 (2.87%)  54/1428 (3.78%) 
Cough † 1  27/127 (21.26%)  22/125 (17.60%)  302/1428 (21.15%)  331/1428 (23.18%) 
Dyspnoea † 1  14/127 (11.02%)  17/125 (13.60%)  339/1428 (23.74%)  359/1428 (25.14%) 
Haemoptysis † 1  5/127 (3.94%)  8/125 (6.40%)  82/1428 (5.74%)  88/1428 (6.16%) 
Nasal congestion † 1  11/127 (8.66%)  4/125 (3.20%)  49/1428 (3.43%)  58/1428 (4.06%) 
Oropharyngeal pain † 1  8/127 (6.30%)  1/125 (0.80%)  51/1428 (3.57%)  55/1428 (3.85%) 
Pneumonitis † 1  10/127 (7.87%)  4/125 (3.20%)  33/1428 (2.31%)  42/1428 (2.94%) 
Productive cough † 1  11/127 (8.66%)  7/125 (5.60%)  94/1428 (6.58%)  105/1428 (7.35%) 
Sinus congestion † 1  8/127 (6.30%)  3/125 (2.40%)  21/1428 (1.47%)  30/1428 (2.10%) 
Wheezing † 1  6/127 (4.72%)  5/125 (4.00%)  71/1428 (4.97%)  80/1428 (5.60%) 
Skin and subcutaneous tissue disorders         
Pruritus † 1  12/127 (9.45%)  5/125 (4.00%)  119/1428 (8.33%)  127/1428 (8.89%) 
Rash † 1  10/127 (7.87%)  5/125 (4.00%)  98/1428 (6.86%)  108/1428 (7.56%) 
Rash maculo-papular † 1  8/127 (6.30%)  4/125 (3.20%)  62/1428 (4.34%)  72/1428 (5.04%) 
Rash pruritic † 1  7/127 (5.51%)  0/125 (0.00%)  37/1428 (2.59%)  42/1428 (2.94%) 
Vascular disorders         
Hypertension † 1  12/127 (9.45%)  6/125 (4.80%)  56/1428 (3.92%)  64/1428 (4.48%) 
Hypotension † 1  7/127 (5.51%)  5/125 (4.00%)  70/1428 (4.90%)  79/1428 (5.53%) 
1
Term from vocabulary, MedDRA 24.1
†
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please email
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02066636    
Other Study ID Numbers: CA209-153
First Submitted: February 14, 2014
First Posted: February 19, 2014
Results First Submitted: September 29, 2022
Results First Posted: October 27, 2022
Last Update Posted: October 27, 2022