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

• ClinicalTrials.gov Identifier: NCT00730639
• Recruitment Status: Completed
• First Posted: August 8, 2008
• Results First Posted: April 15, 2016
• Last Update Posted: December 3, 2021
• Sponsor: Bristol-Myers Squibb
• 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

Participant Flow

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
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

Baseline Characteristics

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
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
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

Outcome Measures

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)

Adverse Events

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
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	--/--	--/--	--/--	--/--	--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Drilon A, Wolchok JD, Carvajal RD, McHenry MB, Hosein F, Harbison CT, Grosso JF, Sznol M. Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol. 2019 Oct 1;5(10):1411-1420. doi: 10.1001/jamaoncol.2019.2187.

Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00730639
• 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: December 3, 2021