Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 3 for:    CheckMate-012
Previous Study | Return to List | Next Study

Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 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: NCT01454102
Recruitment Status : Active, not recruiting
First Posted : October 18, 2011
Results First Posted : August 5, 2019
Last Update Posted : March 5, 2020
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
Interventions Biological: Nivolumab
Drug: Gemcitabine
Drug: Cisplatin
Drug: Pemetrexed
Drug: Paclitaxel
Drug: Carboplatin
Drug: Bevacizumab
Drug: Erlotinib
Biological: Ipilimumab
Enrollment 472
Recruitment Details  
Pre-assignment Details 472 participants were enrolled; 376 participants received at least one dose of study treatment
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Period Title: Overall Study
Started 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14
Completed 12 15 15 12 18 49 22 25 12 13 12 27 33 34 36 13
Not Completed 0 0 0 0 3 3 2 0 1 0 0 4 7 4 3 1
Reason Not Completed
Continuing in the treatment period             0             0             0             0             3             3             2             0             1             0             0             4             7             4             3             1
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin Total
Hide Arm/Group Description Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4 Total of all reporting groups
Overall Number of Baseline Participants 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14 376
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 15 participants 15 participants 12 participants 21 participants 52 participants 24 participants 25 participants 13 participants 13 participants 12 participants 31 participants 40 participants 38 participants 39 participants 14 participants 376 participants
66.2  (6.82) 60.2  (11.20) 58.7  (8.81) 62.9  (9.53) 62.8  (9.41) 67.0  (9.96) 60.5  (6.99) 63.1  (8.31) 63.6  (10.15) 68.7  (12.64) 62.6  (12.65) 61.5  (10.85) 64.9  (11.25) 65.9  (9.36) 64.4  (9.95) 64.9  (9.79) 64.0  (9.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 15 participants 15 participants 12 participants 21 participants 52 participants 24 participants 25 participants 13 participants 13 participants 12 participants 31 participants 40 participants 38 participants 39 participants 14 participants 376 participants
Female
5
  41.7%
9
  60.0%
8
  53.3%
5
  41.7%
13
  61.9%
26
  50.0%
10
  41.7%
12
  48.0%
5
  38.5%
5
  38.5%
8
  66.7%
16
  51.6%
22
  55.0%
21
  55.3%
15
  38.5%
8
  57.1%
188
  50.0%
Male
7
  58.3%
6
  40.0%
7
  46.7%
7
  58.3%
8
  38.1%
26
  50.0%
14
  58.3%
13
  52.0%
8
  61.5%
8
  61.5%
4
  33.3%
15
  48.4%
18
  45.0%
17
  44.7%
24
  61.5%
6
  42.9%
188
  50.0%
1.Primary Outcome
Title Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Time Frame From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14
Measure Type: Count of Participants
Unit of Measure: Participants
SAEs
4
  33.3%
10
  66.7%
8
  53.3%
3
  25.0%
11
  52.4%
23
  44.2%
18
  75.0%
17
  68.0%
3
  23.1%
4
  30.8%
4
  33.3%
12
  38.7%
21
  52.5%
25
  65.8%
25
  64.1%
9
  64.3%
AEs leading to discontinuation
2
  16.7%
5
  33.3%
1
   6.7%
3
  25.0%
3
  14.3%
9
  17.3%
11
  45.8%
13
  52.0%
3
  23.1%
4
  30.8%
1
   8.3%
3
   9.7%
4
  10.0%
10
  26.3%
8
  20.5%
2
  14.3%
Death
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   3.8%
2
   8.3%
3
  12.0%
0
   0.0%
1
   7.7%
1
   8.3%
1
   3.2%
1
   2.5%
4
  10.5%
2
   5.1%
0
   0.0%
2.Primary Outcome
Title Number of Participants Who Experienced Selected Adverse Events
Hide Description

The number of participants who experienced an AE of interest due to any cause is presented. Endocrine, Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, and

Hypersensitivity/Infusion select AEs were identified that are potentially associated with the use of nivolumab, based on the following 4 guiding principles:

  • AEs that may differ in type, frequency, or severity from AEs caused by non-immunotherapies
  • AEs that may require immunosuppression (eg, corticosteroids) as part of their management
  • AEs whose early recognition and management may mitigate severe toxicity
  • AEs for which multiple event terms may be used to describe a single type of AE, thereby necessitating the pooling of terms for full characterization.
Time Frame From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14
Measure Type: Count of Participants
Unit of Measure: Participants
Endorcrine
3
  25.0%
2
  13.3%
0
   0.0%
2
  16.7%
4
  19.0%
8
  15.4%
8
  33.3%
6
  24.0%
3
  23.1%
2
  15.4%
0
   0.0%
4
  12.9%
15
  37.5%
8
  21.1%
12
  30.8%
1
   7.1%
Gastrointestinal
4
  33.3%
6
  40.0%
8
  53.3%
2
  16.7%
10
  47.6%
16
  30.8%
15
  62.5%
12
  48.0%
5
  38.5%
1
   7.7%
1
   8.3%
12
  38.7%
13
  32.5%
11
  28.9%
13
  33.3%
6
  42.9%
Hepatic
0
   0.0%
2
  13.3%
1
   6.7%
0
   0.0%
4
  19.0%
5
   9.6%
7
  29.2%
2
   8.0%
2
  15.4%
0
   0.0%
0
   0.0%
4
  12.9%
13
  32.5%
1
   2.6%
2
   5.1%
0
   0.0%
Pulmonary
2
  16.7%
2
  13.3%
0
   0.0%
2
  16.7%
1
   4.8%
3
   5.8%
3
  12.5%
2
   8.0%
1
   7.7%
2
  15.4%
0
   0.0%
3
   9.7%
3
   7.5%
5
  13.2%
3
   7.7%
1
   7.1%
Renal
1
   8.3%
6
  40.0%
1
   6.7%
1
   8.3%
2
   9.5%
0
   0.0%
2
   8.3%
0
   0.0%
3
  23.1%
0
   0.0%
0
   0.0%
2
   6.5%
2
   5.0%
6
  15.8%
4
  10.3%
4
  28.6%
Skin
3
  25.0%
9
  60.0%
7
  46.7%
5
  41.7%
16
  76.2%
27
  51.9%
15
  62.5%
14
  56.0%
4
  30.8%
2
  15.4%
2
  16.7%
20
  64.5%
20
  50.0%
21
  55.3%
20
  51.3%
7
  50.0%
Hypersensitivity/Infusion Reactions
1
   8.3%
6
  40.0%
7
  46.7%
1
   8.3%
2
   9.5%
4
   7.7%
1
   4.2%
3
  12.0%
2
  15.4%
0
   0.0%
0
   0.0%
1
   3.2%
1
   2.5%
3
   7.9%
1
   2.6%
1
   7.1%
3.Primary Outcome
Title Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests
Hide Description

The number of subjects with selected hepatic laboratory abnormalities is reported.

AST= aspartate aminotransferase; ALT= alanine aminotransferase; ULN= upper limit of normal.

Time Frame From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with baseline and post-baseline measurements
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 15 14 12 20 51 24 24 12 13 11 29 37 37 36 14
Measure Type: Count of Participants
Unit of Measure: Participants
ALT OR AST > 3XULN
0
   0.0%
0
   0.0%
2
  14.3%
1
   8.3%
4
  20.0%
2
   3.9%
6
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.4%
2
   5.4%
1
   2.7%
0
   0.0%
2
  14.3%
ALT OR AST > 5XULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  10.0%
2
   3.9%
4
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.4%
1
   2.7%
0
   0.0%
0
   0.0%
0
   0.0%
ALT OR AST > 10XULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.0%
0
   0.0%
2
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
ALT OR AST > 20XULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
TOTAL BILIRUBIN > 2XULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.0%
1
   2.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
AST or ALT>3XULN with Bilirubin>2XULN within 1 day
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.0%
1
   2.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
AST or ALT>3XULN with Bilirubin>2XULN within 30day
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.0%
1
   2.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests
Hide Description

The number of subjects with selected thyroid laboratory abnormalities is reported. FT3 and FT4 test abnormalities were considered for a 2-week window after the abnormal TSH test date.

TSH= thyroid-stimulating hormone; FT3= Free T3; FT4= Free T4; LLN= lower limit of normal; ULN= upper limit of normal

Time Frame From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with baseline and post-baseline measurements
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 14 14 12 20 51 23 23 12 13 11 29 34 34 28 14
Measure Type: Count of Participants
Unit of Measure: Participants
TSH > ULN
2
  16.7%
3
  21.4%
1
   7.1%
8
  66.7%
12
  60.0%
21
  41.2%
10
  43.5%
7
  30.4%
5
  41.7%
5
  38.5%
2
  18.2%
10
  34.5%
12
  35.3%
11
  32.4%
11
  39.3%
5
  35.7%
TSH > ULN WITH TSH <= ULN AT BASELINE
1
   8.3%
2
  14.3%
1
   7.1%
4
  33.3%
8
  40.0%
13
  25.5%
10
  43.5%
6
  26.1%
5
  41.7%
3
  23.1%
1
   9.1%
7
  24.1%
9
  26.5%
5
  14.7%
8
  28.6%
4
  28.6%
TSH > ULN WITH >=1 FT3/FT4 TEST VALUE < LLN
0
   0.0%
1
   7.1%
0
   0.0%
1
   8.3%
7
  35.0%
3
   5.9%
5
  21.7%
5
  21.7%
3
  25.0%
0
   0.0%
0
   0.0%
6
  20.7%
7
  20.6%
5
  14.7%
4
  14.3%
2
  14.3%
TSH > ULN WITH ALL FT3/FT4 TEST VALUES >= LLN
0
   0.0%
2
  14.3%
1
   7.1%
0
   0.0%
0
   0.0%
4
   7.8%
1
   4.3%
2
   8.7%
2
  16.7%
2
  15.4%
0
   0.0%
1
   3.4%
1
   2.9%
0
   0.0%
2
   7.1%
0
   0.0%
TSH > ULN WITH FT3/FT4 TEST MISSING
2
  16.7%
0
   0.0%
0
   0.0%
7
  58.3%
5
  25.0%
14
  27.5%
4
  17.4%
0
   0.0%
0
   0.0%
3
  23.1%
2
  18.2%
3
  10.3%
4
  11.8%
6
  17.6%
5
  17.9%
3
  21.4%
TSH < LLN
2
  16.7%
7
  50.0%
5
  35.7%
2
  16.7%
7
  35.0%
9
  17.6%
12
  52.2%
9
  39.1%
3
  25.0%
1
   7.7%
6
  54.5%
9
  31.0%
10
  29.4%
6
  17.6%
9
  32.1%
7
  50.0%
TSH < LLN WITH TSH >= LLN AT BASELINE
1
   8.3%
3
  21.4%
1
   7.1%
1
   8.3%
7
  35.0%
9
  17.6%
12
  52.2%
9
  39.1%
3
  25.0%
0
   0.0%
4
  36.4%
9
  31.0%
9
  26.5%
6
  17.6%
9
  32.1%
5
  35.7%
TSH < LLN WITH >=1 FT3/FT4 TEST VALUE > ULN
1
   8.3%
1
   7.1%
0
   0.0%
0
   0.0%
4
  20.0%
4
   7.8%
6
  26.1%
5
  21.7%
2
  16.7%
1
   7.7%
1
   9.1%
6
  20.7%
7
  20.6%
1
   2.9%
1
   3.6%
2
  14.3%
TSH < LLN WITH ALL FT3/FT4 TEST VALUES <= ULN
0
   0.0%
3
  21.4%
1
   7.1%
1
   8.3%
0
   0.0%
1
   2.0%
3
  13.0%
1
   4.3%
1
   8.3%
0
   0.0%
0
   0.0%
2
   6.9%
2
   5.9%
1
   2.9%
1
   3.6%
0
   0.0%
TSH < LLN WITH FT3/FT4 TEST MISSING
1
   8.3%
3
  21.4%
4
  28.6%
1
   8.3%
3
  15.0%
4
   7.8%
3
  13.0%
3
  13.0%
0
   0.0%
0
   0.0%
5
  45.5%
1
   3.4%
1
   2.9%
4
  11.8%
7
  25.0%
5
  35.7%
5.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the percentage of all treated participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria as per investigator assessment. This proportion was multiplied by 100 and expressed as a percentage. BOR was defined as the best response designation recorded between the date of randomization and the date of progression, or the date of subsequent anticancer therapy, whichever occurred first. CR or PR determinations included in the BOR assessment were confirmed by a second scan at least 4 weeks after the criteria for responses were first met. For participants without progression or subsequent therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial progression.
Time Frame From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
41.7
(15.2 to 72.3)
46.7
(21.3 to 73.4)
46.7
(21.3 to 73.4)
16.7
(2.1 to 48.4)
19.0
(5.4 to 41.9)
23.1
(12.5 to 36.8)
20.8
(7.1 to 42.2)
24.0
(9.4 to 45.1)
0
(0.0 to 24.7)
15.4
(1.9 to 45.4)
8.3
(0.2 to 38.5)
22.6
(9.6 to 41.1)
32.5
(18.6 to 49.1)
47.4
(31.0 to 64.2)
38.5
(23.4 to 55.4)
50.0
(23.0 to 77.0)
6.Secondary Outcome
Title Progression-Free Survival Rate (PFSR) at Week 24
Hide Description

Progression-Free Survival (PFS) was defined as the time from the date of first dose of study medication to the date of first disease progression or death, if death occurred within 100 days of the final dose of study drug. Among participants without previous RECIST-defined progression, participants who died beyond 100 days and those who remained alive were censored at the last tumor assessment date (before subsequent therapy).

PFSR at week 24 was defined as the proportion of subjects remaining progression free and surviving at 24 weeks. The proportion was calculated by the product-limit method (Kaplan-Meier estimate), which takes into account censored data, and expressed as a percentage.

Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C10: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm GH: Nivolumab + Ipilimumab Arm IJ: Nivolumab + Ipilimumab Arm K: Nivolumab in Squamous Histology Subjects (NSCLC) Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm C5: Nivolumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression
Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive SQ and NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression
Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity
Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 5 mg/kg Q3W until progression after cycle 4
Overall Number of Participants Analyzed 12 15 15 12 21 52 24 25 13 13 12 31 40 38 39 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
50.5
(18.7 to 75.7)
68.4
(35.9 to 86.8)
34.3
(11.3 to 59.2)
58.3
(27.0 to 80.1)
50.6
(27.7 to 69.7)
39.7
(26.0 to 53.1)
42.8
(22.4 to 61.8)
37.3
(18.1 to 56.7)
50.0
(20.8 to 73.6)
20.5
(3.3 to 47.8)
8.3
(0.5 to 31.1)
49.1
(30.3 to 65.5)
48.0
(31.6 to 62.7)
72.4
(54.7 to 84.1)
39.5
(24.2 to 54.4)
59.3
(27.5 to 81.0)
Time Frame From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Adverse Event Reporting Description Adverse event data was only collected by cohort and not by dose. All participants in "Arm C10: Nivolumab (10 mg/kg) + Paclitaxel + Carboplatin" and "Arm C5: Nivolumab (5 mg/kg) + Paclitaxel + Carboplatin" were monitored for adverse events under a single "Arm C" as a cohort.
 
Arm/Group Title Arm A: Nivolumab + Gemcitabine + Cisplatin Arm J: Nivolumab + Ipilimumab Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm G: Nivolumab + Ipilimumab Arm H: Nivolumab + Ipilimumab Arm I: Nivolumab + Ipilimumab
Hide Arm/Group Description Chemotherapy-naive SQ subjects; GEM 1250 mg/m2 Days 1 and 8 with CIS 75 mg/m2 on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive NSQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression SQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; Nivo 3 mg/kg Q2W as switch maintenance therapy until progression Subjects with any histology and untreated, asymptomatic brain metastases; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 1 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q12W until progression or unacceptable toxicity Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W + Ipi 1 mg/kg Q6W until progression or unacceptable toxicity Chemotherapy-naive NSQ subjects; dose de-escalation design; PEM 500 mg/m2 with CIS 75 mg/m2, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 Chemotherapy-naive subjects with any histology; dose de-escalation design; PAC 200 mg/m2 with CAR AUC 6, both on Day 1 of a Q3W cycle for up to 4 cycles + Nivo 10 mg/kg Q3W until progression after cycle 4 NSQ subjects who completed >= 4 cycles of chemotherapy and are nonprogressors; BEV 15 mg/kg + Nivo 5 mg/kg Q3W until progression Chemotherapy-naive, subjects with EGFR mutations; ERL 150 mg PO, daily + Nivo 3 mg/kg Q2W until progression Chemotherapy-naive subjects with any histology; Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive NSQ subjects; Nivo 1 mg/kg + Ipi 3 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression Chemotherapy-naive SQ subjects; Nivo 3 mg/kg + Ipi 1 mg/kg Q3W for 4 cycles followed by Nivo 3 mg/kg Q2W until progression
All-Cause Mortality
Arm A: Nivolumab + Gemcitabine + Cisplatin Arm J: Nivolumab + Ipilimumab Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm G: Nivolumab + Ipilimumab Arm H: Nivolumab + Ipilimumab Arm I: Nivolumab + Ipilimumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Arm A: Nivolumab + Gemcitabine + Cisplatin Arm J: Nivolumab + Ipilimumab Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm G: Nivolumab + Ipilimumab Arm H: Nivolumab + Ipilimumab Arm I: Nivolumab + Ipilimumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/12 (33.33%)   12/16 (75.00%)   3/13 (23.08%)   4/13 (30.77%)   4/12 (33.33%)   12/31 (38.71%)   21/40 (52.50%)   25/38 (65.79%)   25/39 (64.10%)   10/15 (66.67%)   17/29 (58.62%)   3/12 (25.00%)   11/21 (52.38%)   23/52 (44.23%)   6/9 (66.67%)   12/15 (80.00%)   5/9 (55.56%) 
Blood and lymphatic system disorders                                   
Anaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  2/38 (5.26%)  1/39 (2.56%)  0/15 (0.00%)  4/29 (13.79%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  1/9 (11.11%) 
Bandaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Febrile neutropenia  1  0/12 (0.00%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  3/29 (10.34%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cardiac disorders                                   
Atrial fibrillation  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Atrioventricular block  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cardiac failure  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Myocardial infarction  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pericardial effusion  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Endocrine disorders                                   
Adrenal insufficiency  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/31 (6.45%)  3/40 (7.50%)  1/38 (2.63%)  2/39 (5.13%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  1/9 (11.11%)  0/15 (0.00%)  0/9 (0.00%) 
Hyperthyroidism  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  1/9 (11.11%)  0/15 (0.00%)  0/9 (0.00%) 
Hypophysitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/31 (6.45%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypopituitarism  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Secondary adrenocortical insufficiency  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Eye disorders                                   
Blindness unilateral  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Uveitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Vitreous haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Gastrointestinal disorders                                   
Abdominal pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  1/39 (2.56%)  1/15 (6.67%)  2/29 (6.90%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Ascites  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Colitis  1  0/12 (0.00%)  2/16 (12.50%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  2/38 (5.26%)  3/39 (7.69%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  1/9 (11.11%) 
Colitis ulcerative  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Diarrhoea  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  2/40 (5.00%)  3/38 (7.89%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  1/9 (11.11%)  1/15 (6.67%)  0/9 (0.00%) 
Dysphagia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  2/39 (5.13%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Gastrointestinal haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Impaired gastric emptying  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Intestinal perforation  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Large intestinal haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Nausea  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  2/38 (5.26%)  1/39 (2.56%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Oesophageal fistula  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pancreatitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Small intestinal haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Small intestinal obstruction  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Tongue discolouration  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Vomiting  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  1/38 (2.63%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
General disorders                                   
Asthenia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Chest pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Disease progression  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  1/31 (3.23%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  1/9 (11.11%) 
Fatigue  1  0/12 (0.00%)  2/16 (12.50%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Influenza like illness  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  2/38 (5.26%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pyrexia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  1/38 (2.63%)  2/39 (5.13%)  2/15 (13.33%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hepatobiliary disorders                                   
Autoimmune hepatitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  3/40 (7.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Bile duct stenosis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cholangitis  1  0/12 (0.00%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Immune system disorders                                   
Hypersensitivity  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Infections and infestations                                   
Bronchitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cystitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Device related infection  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Influenza  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Lung infection  1  0/12 (0.00%)  2/16 (12.50%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  2/40 (5.00%)  1/38 (2.63%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  3/52 (5.77%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Meningitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pneumonia  1  1/12 (8.33%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  3/31 (9.68%)  1/40 (2.50%)  2/38 (5.26%)  1/39 (2.56%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  2/9 (22.22%)  2/15 (13.33%)  0/9 (0.00%) 
Sepsis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Skin infection  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Upper respiratory tract infection  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Urinary tract infection  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  1/12 (8.33%)  1/21 (4.76%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Injury, poisoning and procedural complications                                   
Fall  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  2/21 (9.52%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hip fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Humerus fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Infusion related reaction  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  1/9 (11.11%) 
Lumbar vertebral fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Radiation necrosis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Spinal compression fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Investigations                                   
Alanine aminotransferase increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  0/9 (0.00%)  2/15 (13.33%)  0/9 (0.00%) 
Amylase increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Aspartate aminotransferase increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  0/9 (0.00%)  2/15 (13.33%)  0/9 (0.00%) 
Blood bilirubin increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Blood creatinine increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
International normalised ratio increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Lipase increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Neutrophil count decreased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Platelet count decreased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Transaminases increased  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Metabolism and nutrition disorders                                   
Dehydration  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  1/31 (3.23%)  1/40 (2.50%)  1/38 (2.63%)  4/39 (10.26%)  0/15 (0.00%)  1/29 (3.45%)  1/12 (8.33%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Diabetes mellitus  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypercalcaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  1/9 (11.11%)  0/15 (0.00%)  0/9 (0.00%) 
Hypoglycaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypokalaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hyponatraemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  1/9 (11.11%)  0/15 (0.00%)  0/9 (0.00%) 
Latent autoimmune diabetes in adults  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Type 1 diabetes mellitus  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders                                   
Arthritis  1  0/12 (0.00%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Back pain  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  2/40 (5.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  2/29 (6.90%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Bone pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Muscular weakness  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Musculoskeletal pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Myositis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pathological fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                   
Basal cell carcinoma  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cancer pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  1/9 (11.11%) 
Malignant neoplasm progression  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  2/39 (5.13%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  2/9 (22.22%)  1/15 (6.67%)  0/9 (0.00%) 
Skin cancer  1  0/12 (0.00%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Squamous cell carcinoma of skin  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Transitional cell carcinoma  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Tumour pain  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Nervous system disorders                                   
Brain oedema  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cerebrovascular accident  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cognitive disorder  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Embolic cerebral infarction  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Encephalopathy  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Facial nerve disorder  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Headache  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Miller fisher syndrome  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Nervous system disorder  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Paraesthesia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Peripheral motor neuropathy  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Seizure  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Spinal cord compression  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Syncope  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  2/15 (13.33%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Vocal cord paralysis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Psychiatric disorders                                   
Anxiety  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Confusional state  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  2/52 (3.85%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Delirium  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Mental status changes  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Renal and urinary disorders                                   
Acute kidney injury  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  2/38 (5.26%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Nephritis allergic  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Renal salt-wasting syndrome  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Tubulointerstitial nephritis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders                                   
Acute respiratory failure  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Bronchial obstruction  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Chronic obstructive pulmonary disease  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  2/52 (3.85%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cough  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Dyspnoea  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/31 (6.45%)  2/40 (5.00%)  3/38 (7.89%)  4/39 (10.26%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Haemoptysis  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pleural effusion  1  0/12 (0.00%)  2/16 (12.50%)  0/13 (0.00%)  2/13 (15.38%)  0/12 (0.00%)  2/31 (6.45%)  2/40 (5.00%)  2/38 (5.26%)  1/39 (2.56%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  1/21 (4.76%)  2/52 (3.85%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pneumonitis  1  2/12 (16.67%)  1/16 (6.25%)  0/13 (0.00%)  2/13 (15.38%)  0/12 (0.00%)  2/31 (6.45%)  2/40 (5.00%)  2/38 (5.26%)  1/39 (2.56%)  1/15 (6.67%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  2/9 (22.22%)  1/15 (6.67%)  1/9 (11.11%) 
Pneumothorax  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pulmonary embolism  1  0/12 (0.00%)  2/16 (12.50%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Pulmonary haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  1/9 (11.11%) 
Respiratory acidosis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Respiratory distress  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Respiratory failure  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  1/9 (11.11%)  1/15 (6.67%)  0/9 (0.00%) 
Skin and subcutaneous tissue disorders                                   
Petechiae  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Pruritus  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Rash  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/31 (3.23%)  1/40 (2.50%)  1/38 (2.63%)  1/39 (2.56%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Rash maculo-papular  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  2/29 (6.90%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Vascular disorders                                   
Aortic stenosis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Embolism  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  1/38 (2.63%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  2/15 (13.33%)  0/9 (0.00%) 
Haematoma  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypertension  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypotension  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  2/38 (5.26%)  0/39 (0.00%)  2/15 (13.33%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Superior vena cava syndrome  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Thrombosis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Nivolumab + Gemcitabine + Cisplatin Arm J: Nivolumab + Ipilimumab Arm K: Nivolumab In Squamous Histology Subjects (NSCLC) Arm L: Nivolumab In Non-squamous Histology Subjects (NSCLC) Arm M: Nivolumab Arm N: Nivolumab + Ipilimumab Arm O: Nivolumab + Ipilimumab Arm P: Nivolumab + Ipilimumab Arm Q: Nivolumab + Ipilimumab Arm B: Nivolumab + Pemetrexed + Cisplatin Arm C: Nivolumab + Paclitaxel + Carboplatin Arm D: Nivolumab + Bevacizumab Maintenance Arm E: Nivolumab + Erlotinib Arm F: Nivolumab Arm G: Nivolumab + Ipilimumab Arm H: Nivolumab + Ipilimumab Arm I: Nivolumab + Ipilimumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   16/16 (100.00%)   11/13 (84.62%)   13/13 (100.00%)   11/12 (91.67%)   30/31 (96.77%)   33/40 (82.50%)   35/38 (92.11%)   33/39 (84.62%)   15/15 (100.00%)   29/29 (100.00%)   11/12 (91.67%)   21/21 (100.00%)   50/52 (96.15%)   9/9 (100.00%)   15/15 (100.00%)   9/9 (100.00%) 
Blood and lymphatic system disorders                                   
Anaemia  1  8/12 (66.67%)  1/16 (6.25%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  4/31 (12.90%)  5/40 (12.50%)  6/38 (15.79%)  5/39 (12.82%)  2/15 (13.33%)  8/29 (27.59%)  0/12 (0.00%)  0/21 (0.00%)  2/52 (3.85%)  1/9 (11.11%)  1/15 (6.67%)  2/9 (22.22%) 
Granulocytopenia  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Leukopenia  1  1/12 (8.33%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  2/15 (13.33%)  3/29 (10.34%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Lymphadenitis  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Lymphadenopathy  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Lymphopenia  1  1/12 (8.33%)  2/16 (12.50%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  4/29 (13.79%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Neutropenia  1  2/12 (16.67%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  3/29 (10.34%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Polycythaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Thrombocytopenia  1  3/12 (25.00%)  1/16 (6.25%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Cardiac disorders                                   
Angina pectoris  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Atrial fibrillation  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  1/38 (2.63%)  2/39 (5.13%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Atrial flutter  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  1/9 (11.11%)  0/15 (0.00%)  0/9 (0.00%) 
Palpitations  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  3/29 (10.34%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Pericardial effusion  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Sinus tachycardia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  1/21 (4.76%)  0/52 (0.00%)  0/9 (0.00%)  2/15 (13.33%)  0/9 (0.00%) 
Supraventricular tachycardia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Tachycardia  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/31 (0.00%)  1/40 (2.50%)  2/38 (5.26%)  1/39 (2.56%)  1/15 (6.67%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Ear and labyrinth disorders                                   
Deafness  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  2/15 (13.33%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Deafness unilateral  1  0/12 (0.00%)  0/16 (0.00%)  1/13 (7.69%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Ear discomfort  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  2/38 (5.26%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Ear pain  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  3/40 (7.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  1/29 (3.45%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Hypoacusis  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)  1/52 (1.92%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Tinnitus  1  1/12 (8.33%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  0/39 (0.00%)  5/15 (33.33%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Vertigo  1  0/12 (0.00%)  0/16 (0.00%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  1/12 (8.33%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  0/15 (0.00%)  0/9 (0.00%) 
Endocrine disorders                                   
Adrenal insufficiency  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/31 (0.00%)  0/40 (0.00%)  1/38 (2.63%)  4/39 (10.26%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  0/21 (0.00%)  0/52 (0.00%)  0/9 (0.00%)  1/15 (6.67%)  0/9 (0.00%) 
Autoimmune thyroiditis  1  0/12 (0.00%)  1/16 (6.25%)  0/13 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/31 (0.00%)  1/40 (2.50%)  0/38 (0.00%)  0/39 (0.00%)  0/15 (0.00%)  0/29 (0.00%)  0/12 (0.00%)  1/21 (4.76%)