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A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)

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: NCT00730639
Recruitment Status : Active, not recruiting
First Posted : August 8, 2008
Results First Posted : April 15, 2016
Last Update Posted : August 2, 2018
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Metastatic Castration-resistant Prostrate Cancer
Renal Cell Carcinoma
Metastatic Melanoma
Non-small Cell Lung Cancer
Intervention Biological: BMS-936558 (MDX-1106)
Enrollment 395
Recruitment Details  
Pre-assignment Details 395 participants were enrolled and 306 were treated. 89 were not treated because they failed to meet study eligibility criteria or died prior to the initiation of treatment. All participants had received at least 1 prior cancer therapy. Study is on-going.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description 0.1 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg)was administered intravenously (IV) every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, partial response (PR), or stable disease (SD), who subsequently experienced confirmed PD. 0.3 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD. 1.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD. 3.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD. 10 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
Period Title: Overall Study
Started 17 18 86 54 131
Completed 0 0 0 0 0
Not Completed 17 18 86 54 131
Reason Not Completed
Adverse Event             3             0             9             8             23
Complete Response             0             0             2             2             1
Completed Maximum Cycles             0             0             11             3             6
Death             0             0             0             0             2
Disease Progression             12             13             48             32             88
non-specified             0             0             4             2             3
Protocol Violation             0             0             1             0             0
Withdrawal by Subject             0             0             6             3             4
Treatment on-going             2             5             5             4             4
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab Total
Hide Arm/Group Description Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. Total of all reporting groups
Overall Number of Baseline Participants 17 18 86 54 131 306
Hide Baseline Analysis Population Description
All treated participants.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 17 participants 18 participants 86 participants 54 participants 131 participants 306 participants
57.5
(33 to 79)
60.8
(29 to 85)
61.8
(37 to 83)
62.7
(32 to 81)
63.1
(30 to 85)
62.2
(29 to 85)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 18 participants 86 participants 54 participants 131 participants 306 participants
Less than (<) 65 years 13 9 49 30 67 168
Greater than or equal to (>)= 65 years 4 9 37 24 64 138
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 18 participants 86 participants 54 participants 131 participants 306 participants
Female
4
  23.5%
9
  50.0%
26
  30.2%
21
  38.9%
43
  32.8%
103
  33.7%
Male
13
  76.5%
9
  50.0%
60
  69.8%
33
  61.1%
88
  67.2%
203
  66.3%
Tumor Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 18 participants 86 participants 54 participants 131 participants 306 participants
Squamous Non-Small Cell Lung Cancer (SQ NSCLC) 0 0 15 18 21 54
Non-Squamous NSCLC (NSQ NSCLC) 0 0 18 19 37 74
Melanoma 17 18 35 17 20 107
Renal Cell Carcinoma (RCC) 0 0 18 0 16 34
Castrate-Resistant Prostate Cancer (CRC) 0 0 0 0 19 19
MCRPC 0 0 0 0 17 17
NSCLC of Unspecified Histology 0 0 0 0 1 1
1.Primary Outcome
Title Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs
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. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

Time Frame Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
Overall Number of Participants Analyzed 17 18 86 54 131
Measure Type: Number
Unit of Measure: participants
SAE 9 8 37 26 79
Treatment-Related AE 13 14 70 40 93
All Deaths (within 100 days of last dose) 4 4 18 9 40
Treatment-Related Deaths 0 0 1 0 1
Discontinuation of Study Drug due to AEs 3 0 12 12 30
2.Primary Outcome
Title Number of Participants With Abnormal Serum Chemistry Laboratory Values
Hide Description Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine and Total Bilirubin. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.
Time Frame Day 1 up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab who underwent the laboratory test.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
Overall Number of Participants Analyzed 17 18 86 54 131
Measure Type: Number
Unit of Measure: participants
ALP (Grades 1-2) 8 7 21 11 38
ALP (Grades 3-4) 0 0 3 2 3
ALT (Grades 1-2) 6 3 25 13 18
ALT (Grades 3-4) 0 0 1 2 2
AST (Grades 1-2) 6 4 26 13 41
AST (Grades 3-4) 0 2 2 3 2
Creatinine (Grades 1-2) 5 9 21 9 34
Creatinine (Grades 3-4) 0 0 0 0 1
Total Bilirubin (Grades 1-2) 2 1 3 4 3
Total Bilirubin (Grades 3-4) 0 2 0 0 2
3.Primary Outcome
Title Number of Participants With Abnormal Hematology Laboratory Values
Hide Description Hemoglobin, Lymphocytes, Neutrophils, Platelets and Leukocytes. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for Hemoglobin were based on Gr 1: 10.0 - less than (<) lower limit of normal (LLN); Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for Neutrophils were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < lower limits of normal (LLN); Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0. Abnormal values for Leukocytes were based on Gr 1: 3.0 - < LLN; Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0.
Time Frame Day 1 up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab who underwent the laboratory test.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
Overall Number of Participants Analyzed 17 18 86 54 131
Measure Type: Number
Unit of Measure: participants
Hemoglobin (Grades 1-2) 12 12 58 46 101
Hemoglobin (Grades 3-4) 0 0 6 0 6
Lymphocytes (Grades 1-2) 9 15 64 43 101
Lymphocytes (Grades 3-4) 3 3 8 8 19
Neutrophils (Grades 1-2) 4 4 13 6 12
Neutrophils (Grades 3-4) 0 0 1 1 3
Platelets (Grades 1-2) 2 1 9 10 19
Platelets (Grades 3-4) 0 0 0 0 0
Leukocytes (Grades 1-2) 4 4 11 10 13
Leukocytes (Grades 3-4) 0 0 1 0 3
4.Secondary Outcome
Title Immunogenicity Assessment
Hide Description Classification of participants host immune response was based on the following definitions: Anti-Drug Antibody (ADA) Positive Subjects have with at least one ADA positive sample at any time after initiation of treatment. ADA positive subjects were further classified into categories with Persistent Positive defined as an ADA positive sample at 2 or more sequential timepoints at least 8 weeks apart.
Time Frame Day 1 up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and were ADA-evaluable were analyzed.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
Overall Number of Participants Analyzed 14 14 66 46 103
Measure Type: Number
Unit of Measure: participants
ADA Positive 6 2 7 2 4
Persistant Positive 1 0 1 0 0
5.Secondary Outcome
Title Objective Response Rate
Hide Description Tumor response was evaluated by the sponsor based on tumor assessments by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate (ORR) was defined as the proportion of participants who's confirmed best overall response (BOR) is either complete (CR) or partial (PR), where the denominator is the number of treated participants in the population of interest. Response was based on tumor measurements. Responders= complete response (CR) or partial response (PR). CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. 95% Confidence intervals (CIs) were computed using the Clopper Pearson method.
Time Frame Day 1 up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab with an evaluable tumor response were analyzed.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab All Dose Groups
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Overall Number of Participants Analyzed 17 18 35 37 59 129
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SQ NSCLC (n=0,0,15,18,21,54)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
22.2
(6.4 to 47.6)
23.8
(8.2 to 47.2)
16.7
(7.9 to 29.3)
NSQ NSCLC (n=0,0,18,19,37,74)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
5.6
(0.1 to 27.3)
26.3
(9.1 to 51.2)
18.9
(8.0 to 35.2)
17.6
(9.7 to 28.2)
TOTAL NSCLC (n=0,0,33,37,59,129)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
3.0
(0.1 to 15.8)
24.3
(11.8 to 41.2)
20.3
(11.0 to 32.8)
17.1
(11.0 to 24.7)
Melanoma (n=17,18,35,17,20,107)
35.3
(14.2 to 61.7)
27.8
(9.7 to 53.5)
31.4
(16.9 to 49.3)
41.2
(18.4 to 67.1)
20.0
(5.7 to 43.7)
30.8
(22.3 to 40.5)
Renal Cell Carcinoma (RCC) (n=0,0,18,0,16,34)
0 [1] 
(NA to NA)
0 [1] 
(NA to NA)
27.8
(9.7 to 53.5)
0 [1] 
(NA to NA)
31.3
(11.0 to 58.7)
29.4
(15.1 to 47.5)
[1]
There are no participants so confidence interval was not calculated.
6.Secondary Outcome
Title Duration of Tumor Response
Hide Description Duration of tumor response (DOR) was calculated from the first date of response of complete response (CR) or partial response (PR) to the date of the first progressive disease (PD) or the date of death. Duration of response was censored at the last tumor assessment date if a responder did not have PD or death. Nonresponders were not included in the analysis. Median DOR was estimated by Kaplan-Meier analysis.
Time Frame Day 1 up to June 2013, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab with a measurable tumor response were analyzed.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab All Dose Groups
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Overall Number of Participants Analyzed 17 18 35 37 59 129
Median (Full Range)
Unit of Measure: months
SQ NSCLC (n=0,0,15,18,21,54)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [3] 
(3.7 to 30.8)
19.1
(3.7 to 30.5)
NA [3] 
(3.7 to 30.8)
NSQ NSCLC (n=0,0,18,19,37,74)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
14.7
(14.7 to 14.7)
13.6
(5.6 to 17.0)
NA [3] 
(1.4 to 22.7)
14.2
(1.4 to 22.7)
All NSCLC (n=0,0,33,37,59,129)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
14.7
(14.7 to 14.7)
17
(3.7 to 30.8)
19.1
(1.4 to 30.5)
17.0
(1.4 to 30.8)
Mel (n=17,18,35,17,20,107)
NA [3] 
(5.6 to 18.4)
20.7
(4.2 to 21.5)
24.0
(3.9 to 24.9)
17.5
(9.2 to 26.5)
25.7
(17.0 to 26.9)
22.9
(3.9 to 26.9)
RCC (n=0,0,18,0,16,34)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
12.9
(9.2 to 17.5)
NA [1] 
(NA to NA)
12.9
(8.4 to 29.1)
12.9
(8.4 to 29.1)
[1]
There are no participants in this group.
[2]
There are no participants with a response in this group.
[3]
Median duration of response has not been reached.
7.Secondary Outcome
Title Geometric Mean Maximum Serum Concentration (Cmax)
Hide Description Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA). Blood samples were assessed at all doses from a subset of participants. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).
Time Frame 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
Overall Number of Participants Analyzed 15 17 17 13 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (µg/mL)
Cycle 1/Day 1 (n=15,17,17,13,14)
1.9
(23.6%)
7.0
(32.3%)
19.6
(29.5%)
61.3
(26.4%)
191.2
(40.0%)
Cycle 3/Day 1 (n=5,2,10,7,5)
3.7
(42.2%)
17.8
(26.6%)
46.9
(26.1%)
132.0
(19.8%)
475.0
(24.6%)
8.Secondary Outcome
Title Median Time of Maximum Serum Concentration (Tmax)
Hide Description Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed Blood samples were assessed at all doses from a subset of participants. The PK parameter of Tmax was measured in hours (h).
Time Frame 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
Overall Number of Participants Analyzed 15 17 17 13 14
Median (Full Range)
Unit of Measure: hours (h)
Cycle 1/Day 1 (n=15,17,17,13,14)
1.1
(0.3 to 51.0)
1.2
(0.9 to 24.3)
1.2
(0.9 to 48.0)
2.1
(0.8 to 8.0)
3.9
(1.0 to 48.2)
Cycle 3/Day 1 (n=5,2,10,7,5)
8.0
(0.6 to 24.0)
24.7
(1.3 to 48.0)
1.0
(0.9 to 24.1)
4.0
(1.0 to 8.0)
22.3
(1.0 to 24.5)
9.Secondary Outcome
Title Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose
Hide Description Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of AUC was measured in micrograms*hours per milliliter (μg*h/mL).
Time Frame 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
Overall Number of Participants Analyzed 13 15 10 13 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms*hours per milliliter (μg*h/mL
Cycle 1/Day 1 (n=13,15,10,13,12)
279.4
(32.5%)
954.7
(26.9%)
3589.6
(23.8%)
8785.8
(22.7%)
31095.1
(25.4%)
Cycle 3/Day 1 (n=4,2,9,5,3)
1101.4
(26.6%)
3406.1
(12.8%)
10190.4
(25.8%)
30640.3
(17.5%)
99621.7
(26.0%)
10.Secondary Outcome
Title Geometric Mean Total Body Clearance of Drug From Serum (CLT)
Hide Description Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples Blood samples were assessed at all doses from a subset of participants. The PK parameter of CLT was measured in milliliters per hour (mL/h).
Time Frame 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
Overall Number of Participants Analyzed 4 2 9 5 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: milliliters per hour (mL/h)
8.3
(40.0%)
6.9
(17.8%)
8.0
(31.1%)
10.3
(18.1%)
8.5
(6.4%)
11.Secondary Outcome
Title Mean Effective Half-life (T-HALFeff)
Hide Description Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of T-HALFeff was measured in hours (h).
Time Frame 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose or any partial dose of nivolumab and had adequate PK profiles.
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1.0 mg/kg Nivolumab 3.0 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description:
Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each cycle.
Overall Number of Participants Analyzed 4 2 9 5 3
Mean (Standard Deviation)
Unit of Measure: hours (h)
622  (235) 555  (42) 636  (267) 661  (202) 595  (80)
Time Frame Day 1 to 70 days following last dose of study drug up to February 2013
Adverse Event Reporting Description Study initiated: October 2008; Primary endpoint: February 2013
 
Arm/Group Title 0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1 mg/kg Nivolumab 3 mg/kg Nivolumab 10 mg/kg Nivolumab
Hide Arm/Group Description Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. IV solution of 0.3 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. IV solution of 1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. IV solution of 3 milligrams nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle. IV solution of 10 milligrams nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
All-Cause Mortality
0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1 mg/kg Nivolumab 3 mg/kg Nivolumab 10 mg/kg Nivolumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1 mg/kg Nivolumab 3 mg/kg Nivolumab 10 mg/kg Nivolumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/17 (52.94%)   8/18 (44.44%)   37/86 (43.02%)   26/54 (48.15%)   79/131 (60.31%) 
Blood and lymphatic system disorders           
Anaemia  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  2/131 (1.53%) 
Pancytopenia  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Cardiac disorders           
Myocardial infarction  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  1/131 (0.76%) 
Angina unstable  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Cardiac tamponade  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Cardiopulmonary failure  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Palpitations  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Tachycardia  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Pericardial effusion  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Cardiac failure congestive  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Atrial fibrillation  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  3/131 (2.29%) 
Ischaemic cardiomyopathy  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Acute myocardial infarction  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Atrial flutter  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Endocrine disorders           
Hypothyroidism  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Hyperthyroidism  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Adrenal insufficiency  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Secondary adrenocortical insufficiency  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hypophysitis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Eye disorders           
Uveitis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Gastrointestinal disorders           
Abdominal pain lower  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Ascites  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Gastrointestinal perforation  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Small intestinal obstruction  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Abdominal pain upper  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  2/131 (1.53%) 
Colitis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  2/131 (1.53%) 
Diarrhoea  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  6/131 (4.58%) 
Rectal haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Vomiting  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  10/131 (7.63%) 
Abdominal pain  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
Dysphagia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Constipation  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Intussusception  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Abdominal distension  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Abdominal wall haematoma  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Gastrointestinal fistula  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Gastrointestinal haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Intestinal obstruction  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Nausea  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  7/131 (5.34%) 
Gastrointestinal obstruction  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
General disorders           
Pain  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  3/131 (2.29%) 
Chills  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Fatigue  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  2/131 (1.53%) 
Mucosal inflammation  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Multi-organ failure  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Pyrexia  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  6/131 (4.58%) 
Asthenia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Chest pain  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  2/131 (1.53%) 
Oedema peripheral  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Hernia  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Chest discomfort  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Hepatobiliary disorders           
Cholecystitis acute  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hepatitis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Hepatic failure  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Jaundice cholestatic  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Immune system disorders           
Hypersensitivity  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Infections and infestations           
Abdominal infection  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Pneumonia fungal  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Lobar pneumonia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Bronchopulmonary aspergillosis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Gastroenteritis viral  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Infection  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
Lung infection pseudomonal  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Pneumonia klebsiella  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Septic shock  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Pelvic abscess  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Tooth abscess  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Cellulitis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Pneumonia  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  4/54 (7.41%)  5/131 (3.82%) 
Urinary tract infection  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Empyema  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Sepsis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  2/131 (1.53%) 
Appendicitis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Lung infection  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Pyelonephritis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Injury, poisoning and procedural complications           
Laryngeal injury  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Wrist fracture  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Fall  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Femur fracture  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Fibula fracture  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Hip fracture  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Rib fracture  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Investigations           
Lipase increased  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
International normalised ratio increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Blood creatinine increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Transaminases increased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Blood bilirubin increased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Amylase increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Platelet count decreased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Alanine aminotransferase increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Blood alkaline phosphatase increased  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Blood uric acid increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Haemoglobin decreased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Aspartate aminotransferase increased  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Metabolism and nutrition disorders           
Hypercalcaemia  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  0/131 (0.00%) 
Hypophosphataemia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Malnutrition  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Dehydration  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  2/54 (3.70%)  6/131 (4.58%) 
Acidosis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Decreased appetite  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Failure to thrive  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Hyponatraemia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Hypokalaemia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Lactic acidosis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hyperkalaemia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  2/131 (1.53%) 
Musculoskeletal and connective tissue disorders           
Muscular weakness  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Myalgia  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Arthralgia  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Back pain  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  2/131 (1.53%) 
Musculoskeletal pain  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  2/131 (1.53%) 
Myositis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Groin pain  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Flank pain  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Non-small cell lung cancer  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Squamous cell carcinoma  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Chronic myeloid leukaemia  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Lung cancer metastatic  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Metastases to penis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Metastatic malignant melanoma  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Pericardial effusion malignant  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Malignant neoplasm progression  1  3/17 (17.65%)  1/18 (5.56%)  12/86 (13.95%)  5/54 (9.26%)  27/131 (20.61%) 
Brain cancer metastatic  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Malignant soft tissue neoplasm  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Tumour pain  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Bronchial neoplasm  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Gastrointestinal carcinoma  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Metastases to central nervous system  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Metastases to spine  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Myelodysplastic syndrome  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Malignant pleural effusion  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Metastases to peritoneum  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Intracranial tumour haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Nervous system disorders           
Cranial nerve disorder  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Metabolic encephalopathy  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Myoclonus  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Convulsion  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  3/131 (2.29%) 
Headache  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Cerebral infarction  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Neuralgia  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  0/131 (0.00%) 
Speech disorder  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Spinal cord compression  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Central nervous system haemorrhage  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Lethargy  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Neuropathy peripheral  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Cerebellar infarction  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hemiparesis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Psychiatric disorders           
Depression  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Confusional state  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  3/131 (2.29%) 
Mood altered  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Mental status changes  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  2/131 (1.53%) 
Renal and urinary disorders           
Renal failure acute  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  1/54 (1.85%)  4/131 (3.05%) 
Renal tubular necrosis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Urogenital haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Hydronephrosis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Nephrolithiasis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Renal injury  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Renal failure  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Ureteric obstruction  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Tubulointerstitial nephritis  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
Pulmonary embolism  1  0/17 (0.00%)  0/18 (0.00%)  4/86 (4.65%)  0/54 (0.00%)  1/131 (0.76%) 
Chronic obstructive pulmonary disease  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Interstitial lung disease  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Pleural effusion  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  4/131 (3.05%) 
Haemoptysis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  2/131 (1.53%) 
Hypercapnia  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Hypoxia  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  1/54 (1.85%)  4/131 (3.05%) 
Pulmonary haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Acute respiratory distress syndrome  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Atelectasis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Lung infiltration  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Cough  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Dyspnoea  1  0/17 (0.00%)  2/18 (11.11%)  5/86 (5.81%)  2/54 (3.70%)  19/131 (14.50%) 
Pneumonitis  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  4/131 (3.05%) 
Pneumothorax  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Respiratory failure  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  1/131 (0.76%) 
Bronchial haemorrhage  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Skin and subcutaneous tissue disorders           
Rash  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Pruritus  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Swelling face  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Rash macular  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Vascular disorders           
Deep vein thrombosis  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  1/54 (1.85%)  2/131 (1.53%) 
Thrombosis  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Haematoma  1  0/17 (0.00%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hypotension  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  3/131 (2.29%) 
Jugular vein thrombosis  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
0.1 mg/kg Nivolumab 0.3 mg/kg Nivolumab 1 mg/kg Nivolumab 3 mg/kg Nivolumab 10 mg/kg Nivolumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/17 (100.00%)   17/18 (94.44%)   83/86 (96.51%)   51/54 (94.44%)   130/131 (99.24%) 
Blood and lymphatic system disorders           
Anaemia  1  0/17 (0.00%)  3/18 (16.67%)  7/86 (8.14%)  4/54 (7.41%)  18/131 (13.74%) 
Eosinophilia  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Leukopenia  1  1/17 (5.88%)  2/18 (11.11%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Neutropenia  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  0/54 (0.00%)  0/131 (0.00%) 
Lymphopenia  1  2/17 (11.76%)  3/18 (16.67%)  4/86 (4.65%)  5/54 (9.26%)  4/131 (3.05%) 
Cardiac disorders           
Tachycardia  1  0/17 (0.00%)  1/18 (5.56%)  5/86 (5.81%)  0/54 (0.00%)  8/131 (6.11%) 
Ear and labyrinth disorders           
Ear pain  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Cerumen impaction  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Tinnitus  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  2/54 (3.70%)  1/131 (0.76%) 
Endocrine disorders           
Hypothyroidism  1  1/17 (5.88%)  1/18 (5.56%)  5/86 (5.81%)  1/54 (1.85%)  5/131 (3.82%) 
Hyperthyroidism  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Eye disorders           
Eye pain  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  0/131 (0.00%) 
Eyelid ptosis  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Periorbital oedema  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Dry eye  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  2/54 (3.70%)  2/131 (1.53%) 
Visual impairment  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Conjunctival haemorrhage  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Conjunctivitis  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
Lacrimation increased  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  2/54 (3.70%)  1/131 (0.76%) 
Macular degeneration  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Gastrointestinal disorders           
Abdominal pain lower  1  1/17 (5.88%)  1/18 (5.56%)  3/86 (3.49%)  1/54 (1.85%)  4/131 (3.05%) 
Dry mouth  1  2/17 (11.76%)  0/18 (0.00%)  13/86 (15.12%)  5/54 (9.26%)  12/131 (9.16%) 
Flatulence  1  1/17 (5.88%)  2/18 (11.11%)  4/86 (4.65%)  2/54 (3.70%)  1/131 (0.76%) 
Ascites  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Dyspepsia  1  1/17 (5.88%)  3/18 (16.67%)  6/86 (6.98%)  1/54 (1.85%)  12/131 (9.16%) 
Frequent bowel movements  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Abdominal pain upper  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  5/54 (9.26%)  8/131 (6.11%) 
Colitis  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  2/131 (1.53%) 
Diarrhoea  1  3/17 (17.65%)  3/18 (16.67%)  37/86 (43.02%)  23/54 (42.59%)  36/131 (27.48%) 
Vomiting  1  3/17 (17.65%)  3/18 (16.67%)  14/86 (16.28%)  12/54 (22.22%)  29/131 (22.14%) 
Abdominal pain  1  1/17 (5.88%)  2/18 (11.11%)  12/86 (13.95%)  6/54 (11.11%)  12/131 (9.16%) 
Dysphagia  1  1/17 (5.88%)  1/18 (5.56%)  1/86 (1.16%)  4/54 (7.41%)  5/131 (3.82%) 
Constipation  1  6/17 (35.29%)  3/18 (16.67%)  18/86 (20.93%)  15/54 (27.78%)  35/131 (26.72%) 
Gastrooesophageal reflux disease  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  3/54 (5.56%)  3/131 (2.29%) 
Abdominal distension  1  1/17 (5.88%)  2/18 (11.11%)  6/86 (6.98%)  6/54 (11.11%)  14/131 (10.69%) 
Auriculotemporal syndrome  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Nausea  1  2/17 (11.76%)  4/18 (22.22%)  22/86 (25.58%)  17/54 (31.48%)  39/131 (29.77%) 
Toothache  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  0/54 (0.00%)  0/131 (0.00%) 
Abdominal discomfort  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  3/54 (5.56%)  5/131 (3.82%) 
Gastrointestinal obstruction  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Mucous stools  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Gastritis  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  2/131 (1.53%) 
General disorders           
Pain  1  3/17 (17.65%)  0/18 (0.00%)  6/86 (6.98%)  6/54 (11.11%)  5/131 (3.82%) 
Chills  1  0/17 (0.00%)  1/18 (5.56%)  5/86 (5.81%)  4/54 (7.41%)  14/131 (10.69%) 
Fatigue  1  10/17 (58.82%)  8/18 (44.44%)  42/86 (48.84%)  31/54 (57.41%)  75/131 (57.25%) 
Infusion site extravasation  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Sensation of foreign body  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Xerosis  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Axillary pain  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  2/131 (1.53%) 
Disease progression  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Injection site discomfort  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Mucosal inflammation  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  7/131 (5.34%) 
Nodule  1  2/17 (11.76%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  1/131 (0.76%) 
Gait disturbance  1  2/17 (11.76%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  4/131 (3.05%) 
Pyrexia  1  3/17 (17.65%)  6/18 (33.33%)  11/86 (12.79%)  5/54 (9.26%)  26/131 (19.85%) 
Asthenia  1  0/17 (0.00%)  0/18 (0.00%)  6/86 (6.98%)  2/54 (3.70%)  10/131 (7.63%) 
Chest pain  1  1/17 (5.88%)  0/18 (0.00%)  6/86 (6.98%)  4/54 (7.41%)  12/131 (9.16%) 
Oedema peripheral  1  4/17 (23.53%)  2/18 (11.11%)  18/86 (20.93%)  9/54 (16.67%)  24/131 (18.32%) 
Influenza like illness  1  2/17 (11.76%)  1/18 (5.56%)  6/86 (6.98%)  3/54 (5.56%)  2/131 (1.53%) 
Oedema  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  2/54 (3.70%)  4/131 (3.05%) 
Chest discomfort  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  5/54 (9.26%)  10/131 (7.63%) 
Hepatobiliary disorders           
Hyperbilirubinaemia  1  1/17 (5.88%)  2/18 (11.11%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hepatic steatosis  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Immune system disorders           
Seasonal allergy  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  0/54 (0.00%)  4/131 (3.05%) 
Drug hypersensitivity  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Infections and infestations           
Candidiasis  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  2/54 (3.70%)  2/131 (1.53%) 
Sinusitis  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  2/54 (3.70%)  10/131 (7.63%) 
Viral infection  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Cellulitis  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  2/54 (3.70%)  4/131 (3.05%) 
Pneumonia  1  0/17 (0.00%)  0/18 (0.00%)  3/86 (3.49%)  3/54 (5.56%)  5/131 (3.82%) 
Urinary tract infection  1  0/17 (0.00%)  2/18 (11.11%)  5/86 (5.81%)  4/54 (7.41%)  8/131 (6.11%) 
Fungal skin infection  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Oral herpes  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Upper respiratory tract infection  1  2/17 (11.76%)  5/18 (27.78%)  6/86 (6.98%)  3/54 (5.56%)  13/131 (9.92%) 
Nasopharyngitis  1  1/17 (5.88%)  1/18 (5.56%)  2/86 (2.33%)  2/54 (3.70%)  7/131 (5.34%) 
Otitis media  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Rhinitis  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Injury, poisoning and procedural complications           
Contusion  1  0/17 (0.00%)  0/18 (0.00%)  3/86 (3.49%)  5/54 (9.26%)  6/131 (4.58%) 
Fall  1  0/17 (0.00%)  0/18 (0.00%)  5/86 (5.81%)  0/54 (0.00%)  3/131 (2.29%) 
Infusion related reaction  1  0/17 (0.00%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  6/131 (4.58%) 
Procedural pain  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  2/131 (1.53%) 
Investigations           
Neutrophil count increased  1  2/17 (11.76%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Weight increased  1  0/17 (0.00%)  1/18 (5.56%)  5/86 (5.81%)  5/54 (9.26%)  5/131 (3.82%) 
Blood thyroid stimulating hormone increased  1  2/17 (11.76%)  1/18 (5.56%)  2/86 (2.33%)  3/54 (5.56%)  4/131 (3.05%) 
White blood cell count increased  1  1/17 (5.88%)  0/18 (0.00%)  4/86 (4.65%)  1/54 (1.85%)  1/131 (0.76%) 
Blood creatine phosphokinase increased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Blood creatinine decreased  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Blood creatinine increased  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  2/54 (3.70%)  6/131 (4.58%) 
Blood potassium decreased  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Thyroxine free increased  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Weight decreased  1  4/17 (23.53%)  1/18 (5.56%)  11/86 (12.79%)  10/54 (18.52%)  22/131 (16.79%) 
Blood glucose increased  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  4/131 (3.05%) 
Blood bilirubin increased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Blood lactate dehydrogenase increased  1  2/17 (11.76%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Granulocyte count decreased  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Prostatic specific antigen increased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Blood testosterone decreased  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
C-reactive protein increased  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
CD4 lymphocytes decreased  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  3/131 (2.29%) 
Neutrophil count decreased  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  2/131 (1.53%) 
Alanine aminotransferase increased  1  0/17 (0.00%)  1/18 (5.56%)  11/86 (12.79%)  2/54 (3.70%)  6/131 (4.58%) 
Blood alkaline phosphatase increased  1  1/17 (5.88%)  2/18 (11.11%)  3/86 (3.49%)  2/54 (3.70%)  6/131 (4.58%) 
Blood uric acid increased  1  0/17 (0.00%)  0/18 (0.00%)  3/86 (3.49%)  4/54 (7.41%)  3/131 (2.29%) 
Haemoglobin decreased  1  2/17 (11.76%)  3/18 (16.67%)  12/86 (13.95%)  7/54 (12.96%)  18/131 (13.74%) 
Aspartate aminotransferase increased  1  0/17 (0.00%)  1/18 (5.56%)  9/86 (10.47%)  2/54 (3.70%)  3/131 (2.29%) 
Blood phosphorus decreased  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  7/131 (5.34%) 
Thyroxine free decreased  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
White blood cell count decreased  1  2/17 (11.76%)  0/18 (0.00%)  4/86 (4.65%)  2/54 (3.70%)  5/131 (3.82%) 
Metabolism and nutrition disorders           
Hypercalcaemia  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  1/54 (1.85%)  1/131 (0.76%) 
Hypoalbuminaemia  1  1/17 (5.88%)  0/18 (0.00%)  5/86 (5.81%)  2/54 (3.70%)  2/131 (1.53%) 
Hypophosphataemia  1  0/17 (0.00%)  3/18 (16.67%)  10/86 (11.63%)  4/54 (7.41%)  7/131 (5.34%) 
Dehydration  1  3/17 (17.65%)  2/18 (11.11%)  6/86 (6.98%)  3/54 (5.56%)  12/131 (9.16%) 
Hypoglycaemia  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  1/54 (1.85%)  2/131 (1.53%) 
Diabetes mellitus  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Hyperglycaemia  1  5/17 (29.41%)  1/18 (5.56%)  18/86 (20.93%)  4/54 (7.41%)  10/131 (7.63%) 
Hyperuricaemia  1  1/17 (5.88%)  1/18 (5.56%)  7/86 (8.14%)  1/54 (1.85%)  2/131 (1.53%) 
Cachexia  1  1/17 (5.88%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Decreased appetite  1  7/17 (41.18%)  6/18 (33.33%)  31/86 (36.05%)  17/54 (31.48%)  46/131 (35.11%) 
Failure to thrive  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hypomagnesaemia  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  2/54 (3.70%)  4/131 (3.05%) 
Hyponatraemia  1  2/17 (11.76%)  2/18 (11.11%)  8/86 (9.30%)  2/54 (3.70%)  4/131 (3.05%) 
Hypokalaemia  1  0/17 (0.00%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  3/131 (2.29%) 
Hyperkalaemia  1  0/17 (0.00%)  0/18 (0.00%)  5/86 (5.81%)  0/54 (0.00%)  4/131 (3.05%) 
Iron deficiency  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  0/54 (0.00%)  1/131 (0.76%) 
Musculoskeletal and connective tissue disorders           
Muscular weakness  1  3/17 (17.65%)  0/18 (0.00%)  6/86 (6.98%)  4/54 (7.41%)  13/131 (9.92%) 
Musculoskeletal chest pain  1  0/17 (0.00%)  1/18 (5.56%)  8/86 (9.30%)  2/54 (3.70%)  9/131 (6.87%) 
Myalgia  1  1/17 (5.88%)  1/18 (5.56%)  9/86 (10.47%)  5/54 (9.26%)  8/131 (6.11%) 
Arthralgia  1  6/17 (35.29%)  5/18 (27.78%)  21/86 (24.42%)  10/54 (18.52%)  21/131 (16.03%) 
Musculoskeletal stiffness  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  2/54 (3.70%)  4/131 (3.05%) 
Neck pain  1  2/17 (11.76%)  1/18 (5.56%)  5/86 (5.81%)  3/54 (5.56%)  2/131 (1.53%) 
Pain in extremity  1  3/17 (17.65%)  1/18 (5.56%)  10/86 (11.63%)  7/54 (12.96%)  15/131 (11.45%) 
Muscle twitching  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Back pain  1  6/17 (35.29%)  1/18 (5.56%)  14/86 (16.28%)  12/54 (22.22%)  34/131 (25.95%) 
Musculoskeletal pain  1  1/17 (5.88%)  0/18 (0.00%)  11/86 (12.79%)  6/54 (11.11%)  23/131 (17.56%) 
Groin pain  1  3/17 (17.65%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  3/131 (2.29%) 
Muscle spasms  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  3/54 (5.56%)  14/131 (10.69%) 
Neck mass  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Pain in jaw  1  0/17 (0.00%)  1/18 (5.56%)  2/86 (2.33%)  0/54 (0.00%)  3/131 (2.29%) 
Sjogren's syndrome  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Dysplastic naevus  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Tumour pain  1  0/17 (0.00%)  1/18 (5.56%)  6/86 (6.98%)  1/54 (1.85%)  3/131 (2.29%) 
Malignant pleural effusion  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Seborrhoeic keratosis  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  0/131 (0.00%) 
Nervous system disorders           
Balance disorder  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  5/131 (3.82%) 
Syncope  1  1/17 (5.88%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Convulsion  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Headache  1  4/17 (23.53%)  5/18 (27.78%)  13/86 (15.12%)  12/54 (22.22%)  24/131 (18.32%) 
Mental impairment  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Peripheral sensory neuropathy  1  0/17 (0.00%)  2/18 (11.11%)  1/86 (1.16%)  1/54 (1.85%)  2/131 (1.53%) 
Tremor  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  2/54 (3.70%)  4/131 (3.05%) 
Brain oedema  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Hyperaesthesia  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Paraesthesia  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  2/54 (3.70%)  3/131 (2.29%) 
Dizziness  1  3/17 (17.65%)  4/18 (22.22%)  15/86 (17.44%)  9/54 (16.67%)  25/131 (19.08%) 
Neuropathy peripheral  1  0/17 (0.00%)  1/18 (5.56%)  6/86 (6.98%)  4/54 (7.41%)  7/131 (5.34%) 
Somnolence  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  7/131 (5.34%) 
Cerebellar haemorrhage  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Dysgeusia  1  2/17 (11.76%)  0/18 (0.00%)  6/86 (6.98%)  2/54 (3.70%)  13/131 (9.92%) 
Hypoaesthesia  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  5/54 (9.26%)  5/131 (3.82%) 
Sciatica  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Psychiatric disorders           
Depressed mood  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Hallucination  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Insomnia  1  2/17 (11.76%)  3/18 (16.67%)  10/86 (11.63%)  13/54 (24.07%)  17/131 (12.98%) 
Agitation  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  3/131 (2.29%) 
Anxiety  1  2/17 (11.76%)  0/18 (0.00%)  6/86 (6.98%)  6/54 (11.11%)  11/131 (8.40%) 
Depression  1  1/17 (5.88%)  1/18 (5.56%)  6/86 (6.98%)  5/54 (9.26%)  9/131 (6.87%) 
Confusional state  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  0/54 (0.00%)  9/131 (6.87%) 
Renal and urinary disorders           
Proteinuria  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  1/54 (1.85%)  1/131 (0.76%) 
Urogenital haemorrhage  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  2/131 (1.53%) 
Pollakiuria  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  2/54 (3.70%)  6/131 (4.58%) 
Haematuria  1  1/17 (5.88%)  1/18 (5.56%)  2/86 (2.33%)  1/54 (1.85%)  2/131 (1.53%) 
Haemorrhage urinary tract  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  0/131 (0.00%) 
Dysuria  1  2/17 (11.76%)  0/18 (0.00%)  1/86 (1.16%)  2/54 (3.70%)  3/131 (2.29%) 
Urinary retention  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  3/131 (2.29%) 
Reproductive system and breast disorders           
Scrotal oedema  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  1/54 (1.85%)  0/131 (0.00%) 
Genital erythema  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Vaginal haemorrhage  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Respiratory, thoracic and mediastinal disorders           
Epistaxis  1  1/17 (5.88%)  0/18 (0.00%)  4/86 (4.65%)  1/54 (1.85%)  5/131 (3.82%) 
Pulmonary embolism  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Sinus congestion  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  2/54 (3.70%)  10/131 (7.63%) 
Wheezing  1  0/17 (0.00%)  0/18 (0.00%)  5/86 (5.81%)  4/54 (7.41%)  7/131 (5.34%) 
Upper respiratory tract congestion  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  2/54 (3.70%)  0/131 (0.00%) 
Pleural effusion  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  2/54 (3.70%)  9/131 (6.87%) 
Rhinitis allergic  1  1/17 (5.88%)  0/18 (0.00%)  6/86 (6.98%)  1/54 (1.85%)  4/131 (3.05%) 
Sneezing  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  3/131 (2.29%) 
Dry throat  1  2/17 (11.76%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  1/131 (0.76%) 
Dysphonia  1  2/17 (11.76%)  0/18 (0.00%)  3/86 (3.49%)  5/54 (9.26%)  9/131 (6.87%) 
Haemoptysis  1  0/17 (0.00%)  0/18 (0.00%)  4/86 (4.65%)  2/54 (3.70%)  10/131 (7.63%) 
Hypoxia  1  0/17 (0.00%)  0/18 (0.00%)  4/86 (4.65%)  5/54 (9.26%)  1/131 (0.76%) 
Rhinorrhoea  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  7/131 (5.34%) 
Lung infiltration  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  1/54 (1.85%)  0/131 (0.00%) 
Oropharyngeal pain  1  0/17 (0.00%)  1/18 (5.56%)  4/86 (4.65%)  5/54 (9.26%)  12/131 (9.16%) 
Respiratory tract congestion  1  0/17 (0.00%)  0/18 (0.00%)  2/86 (2.33%)  4/54 (7.41%)  0/131 (0.00%) 
Upper-airway cough syndrome  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  0/54 (0.00%)  6/131 (4.58%) 
Cough  1  6/17 (35.29%)  3/18 (16.67%)  21/86 (24.42%)  17/54 (31.48%)  42/131 (32.06%) 
Dyspnoea  1  0/17 (0.00%)  2/18 (11.11%)  22/86 (25.58%)  17/54 (31.48%)  25/131 (19.08%) 
Dyspnoea exertional  1  4/17 (23.53%)  2/18 (11.11%)  4/86 (4.65%)  4/54 (7.41%)  15/131 (11.45%) 
Nasal congestion  1  1/17 (5.88%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  7/131 (5.34%) 
Productive cough  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  6/54 (11.11%)  7/131 (5.34%) 
Throat irritation  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Skin and subcutaneous tissue disorders           
Dermatitis  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  1/131 (0.76%) 
Night sweats  1  2/17 (11.76%)  1/18 (5.56%)  4/86 (4.65%)  3/54 (5.56%)  8/131 (6.11%) 
Skin hyperpigmentation  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Vitiligo  1  3/17 (17.65%)  1/18 (5.56%)  6/86 (6.98%)  2/54 (3.70%)  0/131 (0.00%) 
Rash maculo-papular  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  0/54 (0.00%)  1/131 (0.76%) 
Urticaria  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  5/54 (9.26%)  2/131 (1.53%) 
Actinic keratosis  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  2/54 (3.70%)  0/131 (0.00%) 
Dermatitis acneiform  1  2/17 (11.76%)  1/18 (5.56%)  0/86 (0.00%)  4/54 (7.41%)  1/131 (0.76%) 
Dermatitis contact  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  1/54 (1.85%)  1/131 (0.76%) 
Hyperhidrosis  1  1/17 (5.88%)  0/18 (0.00%)  5/86 (5.81%)  3/54 (5.56%)  6/131 (4.58%) 
Melanosis  1  1/17 (5.88%)  0/18 (0.00%)  0/86 (0.00%)  0/54 (0.00%)  0/131 (0.00%) 
Rash  1  3/17 (17.65%)  5/18 (27.78%)  27/86 (31.40%)  13/54 (24.07%)  25/131 (19.08%) 
Dry skin  1  4/17 (23.53%)  0/18 (0.00%)  7/86 (8.14%)  1/54 (1.85%)  17/131 (12.98%) 
Facial wasting  1  2/17 (11.76%)  0/18 (0.00%)  3/86 (3.49%)  0/54 (0.00%)  2/131 (1.53%) 
Sunburn  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  3/54 (5.56%)  1/131 (0.76%) 
Pruritus  1  2/17 (11.76%)  4/18 (22.22%)  21/86 (24.42%)  8/54 (14.81%)  20/131 (15.27%) 
Erythema  1  0/17 (0.00%)  0/18 (0.00%)  1/86 (1.16%)  3/54 (5.56%)  8/131 (6.11%) 
Lentigo  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Rash pruritic  1  0/17 (0.00%)  1/18 (5.56%)  3/86 (3.49%)  1/54 (1.85%)  5/131 (3.82%) 
Skin lesion  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  1/54 (1.85%)  2/131 (1.53%) 
Subcutaneous nodule  1  1/17 (5.88%)  0/18 (0.00%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  1/17 (5.88%)  0/18 (0.00%)  2/86 (2.33%)  1/54 (1.85%)  1/131 (0.76%) 
Hypertension  1  3/17 (17.65%)  3/18 (16.67%)  6/86 (6.98%)  4/54 (7.41%)  6/131 (4.58%) 
Flushing  1  1/17 (5.88%)  1/18 (5.56%)  3/86 (3.49%)  4/54 (7.41%)  4/131 (3.05%) 
Lymphoedema  1  0/17 (0.00%)  1/18 (5.56%)  0/86 (0.00%)  1/54 (1.85%)  1/131 (0.76%) 
Hypotension  1  2/17 (11.76%)  1/18 (5.56%)  6/86 (6.98%)  7/54 (12.96%)  16/131 (12.21%) 
Orthostatic hypotension  1  1/17 (5.88%)  0/18 (0.00%)  3/86 (3.49%)  1/54 (1.85%)  2/131 (1.53%) 
Haemorrhage  1  0/17 (0.00%)  1/18 (5.56%)  1/86 (1.16%)  0/54 (0.00%)  0/131 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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 trials primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00730639     History of Changes
Other Study ID Numbers: CA209-003
MDX1106-03 ( Other Identifier: BMS )
First Submitted: August 4, 2008
First Posted: August 8, 2008
Results First Submitted: February 22, 2016
Results First Posted: April 15, 2016
Last Update Posted: August 2, 2018