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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00730639
Collaborator
Ono Pharmaceutical Co. Ltd (Industry)
395
Enrollment
13
Locations
5
Arms
145.7
Actual Duration (Months)
30.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and effectiveness of MDX-1106 in patients with certain types of cancer. Another purpose is to determine how MDX-1106 is absorbed and distributed within the body, and how it's eventually eliminated.

Condition or Disease Intervention/Treatment Phase
  • Biological: BMS-936558 (MDX-1106)
  • Biological: BMS-936558 (MDX-1106)
  • Biological: BMS-936558 (MDX-1106)
  • Biological: BMS-936558 (MDX-1106)
  • Biological: BMS-936558 (MDX-1106)
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
395 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies
Actual Study Start Date :
Oct 30, 2008
Actual Primary Completion Date :
Feb 4, 2013
Actual Study Completion Date :
Dec 22, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Melanoma - BMS-936558 (MDX-1106)

Biological: BMS-936558 (MDX-1106)
Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Other Names:
  • BMS-936558

    		•
    Experimental: RCC - BMS-936558 (MDX-1106)

    Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Names:
  • BMS-936558

    		•
    Experimental: mCRPC - BMS-936558 (MDX-1106)

    Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Names:
  • BMS-936558

    		•
    Experimental: NSCLC - BMS-936558 (MDX-1106)

    Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Names:
  • BMS-936558

    		•
    Experimental: CRC - BMS-936558 (MDX-1106)

    Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Names:
  • BMS-936558

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs [Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years]

      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.

    2. Number of Participants With Abnormal Serum Chemistry Laboratory Values [Day 1 up to June 2013, approximately 4 years]

      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.

    3. Number of Participants With Abnormal Hematology Laboratory Values [Day 1 up to June 2013, approximately 4 years]

      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.

    Secondary Outcome Measures

    1. Immunogenicity Assessment [Day 1 up to June 2013, approximately 4 years]

      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.

    2. Objective Response Rate [Day 1 up to June 2013, approximately 4 years]

      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.

    3. Duration of Tumor Response [Day 1 up to June 2013, approximately 4 years]

      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.

    4. Geometric Mean Maximum Serum Concentration (Cmax) [1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3]

      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).

    5. Median Time of Maximum Serum Concentration (Tmax) [1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3]

      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).

    6. Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose [1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3]

      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).

    7. Geometric Mean Total Body Clearance of Drug From Serum (CLT) [1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3]

      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).

    8. Mean Effective Half-life (T-HALFeff) [1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

    Inclusion Criteria:

    • Subjects must have mCRPC,RCC, MEL, Non-small-cell lung cancer (NSCLC), or Colorectal Cancer (CRC), that is advanced (non-resectable), or recurrent and for which no alternative, curative standard exists

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

    • Must have at least 1 measurable lesion

    • Subjects with mCRPC and with only non-measurable bone lesions must have either progression new lesions or have Prostate-specific antigen (PSA) progression within the 6-week period before study administration

    • At least 1 and up to 5 prior systemic therapies for advanced/recurrent disease

    • Prior treated brain or meningeal metastases must be without Magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids for at least 2 weeks before study drug administration

    • Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration

    • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids must be discontinued at least 2 weeks before study drug administration

    • Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration

    Exclusion Criteria:

    • History of severe hypersensitivity reactions to other Monoclonal antibody (mAb)s

    • Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy

    • Prior therapy with an anti-Programmed death-1 (PD-1), anti-PD-L1, anti-PD-L2, or anti- Cytotoxic t-lymphocyte antigen-4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)

    • Known history of Human Immunodeficiency Virus

    • Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)

    • Underlying medical conditions that will make the administration of study drug hazardous

    • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids

    • Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pinnacle Oncology Hematology Scottsdale Arizona United States 85258
    2 Yale University School Of Medicine New Haven Connecticut United States 06520
    3 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612-9497
    4 Johns Hopkins University Baltimore Maryland United States 21231
    5 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    6 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    7 Massachusetts General Hospital Boston Massachusetts United States 02215
    8 University Of Michigan Cancer Center Ann Arbor Michigan United States 48109
    9 Memorial Sloan Kettering Nassau New York New York United States 10065
    10 Carolina Biooncology Institute Huntersville North Carolina United States 28078
    11 Christ Hospital Cincinnati Ohio United States 45219
    12 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    13 Vanderbilt-Ingram Cancer Ctr Nashville Tennessee United States 37232

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Ono Pharmaceutical Co. Ltd

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00730639
    Other Study ID Numbers:
    • CA209-003
    • MDX1106-03
    First Posted:
    Aug 8, 2008
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma, Renal Cell
    Nivolumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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

    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 Participants 17 18 86 54 131 306
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    57.5
    60.8
    61.8
    62.7
    63.1
    62.2
    Age, Customized (participants) [Number]
    Less than (<) 65 years
    13
    76.5%
    9
    50%
    49
    57%
    30
    55.6%
    67
    51.1%
    168
    54.9%
    Greater than or equal to (>)= 65 years
    4
    23.5%
    9
    50%
    37
    43%
    24
    44.4%
    64
    48.9%
    138
    45.1%
    Sex: Female, Male (Count of Participants)
    Female
    4
    23.5%
    9
    50%
    26
    30.2%
    21
    38.9%
    43
    32.8%
    103
    33.7%
    Male
    13
    76.5%
    9
    50%
    60
    69.8%
    33
    61.1%
    88
    67.2%
    203
    66.3%
    Tumor Type (participants) [Number]
    Squamous Non-Small Cell Lung Cancer (SQ NSCLC)
    0
    0%
    0
    0%
    15
    17.4%
    18
    33.3%
    21
    16%
    54
    17.6%
    Non-Squamous NSCLC (NSQ NSCLC)
    0
    0%
    0
    0%
    18
    20.9%
    19
    35.2%
    37
    28.2%
    74
    24.2%
    Melanoma
    17
    100%
    18
    100%
    35
    40.7%
    17
    31.5%
    20
    15.3%
    107
    35%
    Renal Cell Carcinoma (RCC)
    0
    0%
    0
    0%
    18
    20.9%
    0
    0%
    16
    12.2%
    34
    11.1%
    Castrate-Resistant Prostate Cancer (CRC)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    14.5%
    19
    6.2%
    MCRPC
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    17
    13%
    17
    5.6%
    NSCLC of Unspecified Histology
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    1
    0.3%

    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.
    Measure Participants 17 18 86 54 131
    SAE
    9
    52.9%
    8
    44.4%
    37
    43%
    26
    48.1%
    79
    60.3%
    Treatment-Related AE
    13
    76.5%
    14
    77.8%
    70
    81.4%
    40
    74.1%
    93
    71%
    All Deaths (within 100 days of last dose)
    4
    23.5%
    4
    22.2%
    18
    20.9%
    9
    16.7%
    40
    30.5%
    Treatment-Related Deaths
    0
    0%
    0
    0%
    1
    1.2%
    0
    0%
    1
    0.8%
    Discontinuation of Study Drug due to AEs
    3
    17.6%
    0
    0%
    12
    14%
    12
    22.2%
    30
    22.9%
    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.
    Measure Participants 17 18 86 54 131
    ALP (Grades 1-2)
    8
    47.1%
    7
    38.9%
    21
    24.4%
    11
    20.4%
    38
    29%
    ALP (Grades 3-4)
    0
    0%
    0
    0%
    3
    3.5%
    2
    3.7%
    3
    2.3%
    ALT (Grades 1-2)
    6
    35.3%
    3
    16.7%
    25
    29.1%
    13
    24.1%
    18
    13.7%
    ALT (Grades 3-4)
    0
    0%
    0
    0%
    1
    1.2%
    2
    3.7%
    2
    1.5%
    AST (Grades 1-2)
    6
    35.3%
    4
    22.2%
    26
    30.2%
    13
    24.1%
    41
    31.3%
    AST (Grades 3-4)
    0
    0%
    2
    11.1%
    2
    2.3%
    3
    5.6%
    2
    1.5%
    Creatinine (Grades 1-2)
    5
    29.4%
    9
    50%
    21
    24.4%
    9
    16.7%
    34
    26%
    Creatinine (Grades 3-4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    Total Bilirubin (Grades 1-2)
    2
    11.8%
    1
    5.6%
    3
    3.5%
    4
    7.4%
    3
    2.3%
    Total Bilirubin (Grades 3-4)
    0
    0%
    2
    11.1%
    0
    0%
    0
    0%
    2
    1.5%
    3. 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.
    Measure Participants 14 14 66 46 103
    ADA Positive
    6
    35.3%
    2
    11.1%
    7
    8.1%
    2
    3.7%
    4
    3.1%
    Persistant Positive
    1
    5.9%
    0
    0%
    1
    1.2%
    0
    0%
    0
    0%
    4. 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.
    Measure Participants 17 18 35 37 59 129
    SQ NSCLC (n=0,0,15,18,21,54)
    0
    0%
    0
    0%
    0
    0%
    22.2
    41.1%
    23.8
    18.2%
    16.7
    5.5%
    NSQ NSCLC (n=0,0,18,19,37,74)
    0
    0%
    0
    0%
    5.6
    6.5%
    26.3
    48.7%
    18.9
    14.4%
    17.6
    5.8%
    TOTAL NSCLC (n=0,0,33,37,59,129)
    0
    0%
    0
    0%
    3.0
    3.5%
    24.3
    45%
    20.3
    15.5%
    17.1
    5.6%
    Melanoma (n=17,18,35,17,20,107)
    35.3
    207.6%
    27.8
    154.4%
    31.4
    36.5%
    41.2
    76.3%
    20.0
    15.3%
    30.8
    10.1%
    Renal Cell Carcinoma (RCC) (n=0,0,18,0,16,34)
    0
    0%
    0
    0%
    27.8
    32.3%
    0
    0%
    31.3
    23.9%
    29.4
    9.6%
    5. 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.
    Measure Participants 17 18 35 37 59 129
    SQ NSCLC (n=0,0,15,18,21,54)
    NA
    NA
    NA
    NA
    19.1
    NA
    NSQ NSCLC (n=0,0,18,19,37,74)
    NA
    NA
    14.7
    13.6
    NA
    14.2
    All NSCLC (n=0,0,33,37,59,129)
    NA
    NA
    14.7
    17
    19.1
    17.0
    Mel (n=17,18,35,17,20,107)
    NA
    20.7
    24.0
    17.5
    25.7
    22.9
    RCC (n=0,0,18,0,16,34)
    NA
    NA
    12.9
    NA
    12.9
    12.9
    6. 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.
    Measure Participants 15 17 17 13 14
    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)
    7. 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.
    Measure Participants 17 18 86 54 131
    Hemoglobin (Grades 1-2)
    12
    70.6%
    12
    66.7%
    58
    67.4%
    46
    85.2%
    101
    77.1%
    Hemoglobin (Grades 3-4)
    0
    0%
    0
    0%
    6
    7%
    0
    0%
    6
    4.6%
    Lymphocytes (Grades 1-2)
    9
    52.9%
    15
    83.3%
    64
    74.4%
    43
    79.6%
    101
    77.1%
    Lymphocytes (Grades 3-4)
    3
    17.6%
    3
    16.7%
    8
    9.3%
    8
    14.8%
    19
    14.5%
    Neutrophils (Grades 1-2)
    4
    23.5%
    4
    22.2%
    13
    15.1%
    6
    11.1%
    12
    9.2%
    Neutrophils (Grades 3-4)
    0
    0%
    0
    0%
    1
    1.2%
    1
    1.9%
    3
    2.3%
    Platelets (Grades 1-2)
    2
    11.8%
    1
    5.6%
    9
    10.5%
    10
    18.5%
    19
    14.5%
    Platelets (Grades 3-4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Leukocytes (Grades 1-2)
    4
    23.5%
    4
    22.2%
    11
    12.8%
    10
    18.5%
    13
    9.9%
    Leukocytes (Grades 3-4)
    0
    0%
    0
    0%
    1
    1.2%
    0
    0%
    3
    2.3%
    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.
    Measure Participants 15 17 17 13 14
    Cycle 1/Day 1 (n=15,17,17,13,14)
    1.1
    1.2
    1.2
    2.1
    3.9
    Cycle 3/Day 1 (n=5,2,10,7,5)
    8.0
    24.7
    1.0
    4.0
    22.3
    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.
    Measure Participants 13 15 10 13 12
    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.
    Measure Participants 4 2 9 5 3
    Geometric Mean (Geometric Coefficient of Variation) [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.
    Measure Participants 4 2 9 5 3
    Mean (Standard Deviation) [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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/17 (52.9%) 8/18 (44.4%) 37/86 (43%) 26/54 (48.1%) 79/131 (60.3%)
    Blood and lymphatic system disorders
    Anaemia 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 2/131 (1.5%)
    Pancytopenia 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Cardiac disorders
    Myocardial infarction 0/17 (0%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 1/131 (0.8%)
    Angina unstable 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Cardiac tamponade 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Cardiopulmonary failure 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Palpitations 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Tachycardia 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Pericardial effusion 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Cardiac failure congestive 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Atrial fibrillation 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 3/131 (2.3%)
    Ischaemic cardiomyopathy 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Acute myocardial infarction 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Atrial flutter 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Endocrine disorders
    Hypothyroidism 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Hyperthyroidism 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Adrenal insufficiency 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Secondary adrenocortical insufficiency 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hypophysitis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Eye disorders
    Uveitis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Gastrointestinal disorders
    Abdominal pain lower 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Ascites 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Gastrointestinal perforation 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Small intestinal obstruction 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Abdominal pain upper 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 2/131 (1.5%)
    Colitis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 2/131 (1.5%)
    Diarrhoea 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 6/131 (4.6%)
    Rectal haemorrhage 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Vomiting 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 10/131 (7.6%)
    Abdominal pain 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    Dysphagia 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Constipation 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Intussusception 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Abdominal distension 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Abdominal wall haematoma 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Gastrointestinal fistula 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Gastrointestinal haemorrhage 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Intestinal obstruction 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Nausea 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 7/131 (5.3%)
    Gastrointestinal obstruction 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    General disorders
    Pain 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 3/131 (2.3%)
    Chills 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Fatigue 0/17 (0%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 2/131 (1.5%)
    Mucosal inflammation 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Multi-organ failure 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Pyrexia 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 6/131 (4.6%)
    Asthenia 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Chest pain 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 2/131 (1.5%)
    Oedema peripheral 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Hernia 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Chest discomfort 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Hepatobiliary disorders
    Cholecystitis acute 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hepatitis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Hepatic failure 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Jaundice cholestatic 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Immune system disorders
    Hypersensitivity 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Infections and infestations
    Abdominal infection 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Pneumonia fungal 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Lobar pneumonia 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Bronchopulmonary aspergillosis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Gastroenteritis viral 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Infection 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    Lung infection pseudomonal 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Pneumonia klebsiella 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Septic shock 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Pelvic abscess 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Tooth abscess 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Cellulitis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Pneumonia 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 4/54 (7.4%) 5/131 (3.8%)
    Urinary tract infection 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Empyema 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Sepsis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 2/131 (1.5%)
    Appendicitis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Lung infection 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Pyelonephritis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Injury, poisoning and procedural complications
    Laryngeal injury 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Wrist fracture 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Fall 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Femur fracture 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Fibula fracture 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Hip fracture 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Rib fracture 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Investigations
    Lipase increased 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    International normalised ratio increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Blood creatinine increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Transaminases increased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Blood bilirubin increased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Amylase increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Platelet count decreased 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Alanine aminotransferase increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Blood alkaline phosphatase increased 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Blood uric acid increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Haemoglobin decreased 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Aspartate aminotransferase increased 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Metabolism and nutrition disorders
    Hypercalcaemia 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 0/131 (0%)
    Hypophosphataemia 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Malnutrition 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Dehydration 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 2/54 (3.7%) 6/131 (4.6%)
    Acidosis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Decreased appetite 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Failure to thrive 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Hyponatraemia 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Hypokalaemia 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Lactic acidosis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hyperkalaemia 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 2/131 (1.5%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Myalgia 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Arthralgia 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Back pain 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 2/131 (1.5%)
    Musculoskeletal pain 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 2/131 (1.5%)
    Myositis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Groin pain 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Flank pain 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Non-small cell lung cancer 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Squamous cell carcinoma 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Chronic myeloid leukaemia 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Lung cancer metastatic 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Metastases to penis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Metastatic malignant melanoma 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Pericardial effusion malignant 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Malignant neoplasm progression 3/17 (17.6%) 1/18 (5.6%) 12/86 (14%) 5/54 (9.3%) 27/131 (20.6%)
    Brain cancer metastatic 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Malignant soft tissue neoplasm 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Tumour pain 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Bronchial neoplasm 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Gastrointestinal carcinoma 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Metastases to central nervous system 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Metastases to spine 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Myelodysplastic syndrome 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Malignant pleural effusion 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Metastases to peritoneum 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Intracranial tumour haemorrhage 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Nervous system disorders
    Cranial nerve disorder 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Metabolic encephalopathy 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Myoclonus 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Convulsion 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 3/131 (2.3%)
    Headache 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Cerebral infarction 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Neuralgia 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 0/131 (0%)
    Speech disorder 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Spinal cord compression 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Central nervous system haemorrhage 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Lethargy 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Neuropathy peripheral 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Cerebellar infarction 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hemiparesis 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Psychiatric disorders
    Depression 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Confusional state 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 3/131 (2.3%)
    Mood altered 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Mental status changes 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 2/131 (1.5%)
    Renal and urinary disorders
    Renal failure acute 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 1/54 (1.9%) 4/131 (3.1%)
    Renal tubular necrosis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Urogenital haemorrhage 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Hydronephrosis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Nephrolithiasis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Renal injury 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Renal failure 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Ureteric obstruction 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Tubulointerstitial nephritis 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    Pulmonary embolism 0/17 (0%) 0/18 (0%) 4/86 (4.7%) 0/54 (0%) 1/131 (0.8%)
    Chronic obstructive pulmonary disease 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Interstitial lung disease 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Pleural effusion 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 4/131 (3.1%)
    Haemoptysis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 2/131 (1.5%)
    Hypercapnia 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Hypoxia 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 1/54 (1.9%) 4/131 (3.1%)
    Pulmonary haemorrhage 0/17 (0%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Acute respiratory distress syndrome 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Atelectasis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Lung infiltration 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Cough 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Dyspnoea 0/17 (0%) 2/18 (11.1%) 5/86 (5.8%) 2/54 (3.7%) 19/131 (14.5%)
    Pneumonitis 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 4/131 (3.1%)
    Pneumothorax 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Respiratory failure 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 1/131 (0.8%)
    Bronchial haemorrhage 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Pruritus 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Swelling face 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Rash macular 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Vascular disorders
    Deep vein thrombosis 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 1/54 (1.9%) 2/131 (1.5%)
    Thrombosis 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Haematoma 0/17 (0%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hypotension 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 3/131 (2.3%)
    Jugular vein thrombosis 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Other (Not Including 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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/17 (100%) 17/18 (94.4%) 83/86 (96.5%) 51/54 (94.4%) 130/131 (99.2%)
    Blood and lymphatic system disorders
    Anaemia 0/17 (0%) 3/18 (16.7%) 7/86 (8.1%) 4/54 (7.4%) 18/131 (13.7%)
    Eosinophilia 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Leukopenia 1/17 (5.9%) 2/18 (11.1%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Neutropenia 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 0/54 (0%) 0/131 (0%)
    Lymphopenia 2/17 (11.8%) 3/18 (16.7%) 4/86 (4.7%) 5/54 (9.3%) 4/131 (3.1%)
    Cardiac disorders
    Tachycardia 0/17 (0%) 1/18 (5.6%) 5/86 (5.8%) 0/54 (0%) 8/131 (6.1%)
    Ear and labyrinth disorders
    Ear pain 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Cerumen impaction 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Tinnitus 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 2/54 (3.7%) 1/131 (0.8%)
    Endocrine disorders
    Hypothyroidism 1/17 (5.9%) 1/18 (5.6%) 5/86 (5.8%) 1/54 (1.9%) 5/131 (3.8%)
    Hyperthyroidism 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Eye disorders
    Eye pain 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 0/131 (0%)
    Eyelid ptosis 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Periorbital oedema 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Dry eye 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 2/54 (3.7%) 2/131 (1.5%)
    Visual impairment 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Conjunctival haemorrhage 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Conjunctivitis 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    Lacrimation increased 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 2/54 (3.7%) 1/131 (0.8%)
    Macular degeneration 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Gastrointestinal disorders
    Abdominal pain lower 1/17 (5.9%) 1/18 (5.6%) 3/86 (3.5%) 1/54 (1.9%) 4/131 (3.1%)
    Dry mouth 2/17 (11.8%) 0/18 (0%) 13/86 (15.1%) 5/54 (9.3%) 12/131 (9.2%)
    Flatulence 1/17 (5.9%) 2/18 (11.1%) 4/86 (4.7%) 2/54 (3.7%) 1/131 (0.8%)
    Ascites 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Dyspepsia 1/17 (5.9%) 3/18 (16.7%) 6/86 (7%) 1/54 (1.9%) 12/131 (9.2%)
    Frequent bowel movements 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Abdominal pain upper 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 5/54 (9.3%) 8/131 (6.1%)
    Colitis 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 2/131 (1.5%)
    Diarrhoea 3/17 (17.6%) 3/18 (16.7%) 37/86 (43%) 23/54 (42.6%) 36/131 (27.5%)
    Vomiting 3/17 (17.6%) 3/18 (16.7%) 14/86 (16.3%) 12/54 (22.2%) 29/131 (22.1%)
    Abdominal pain 1/17 (5.9%) 2/18 (11.1%) 12/86 (14%) 6/54 (11.1%) 12/131 (9.2%)
    Dysphagia 1/17 (5.9%) 1/18 (5.6%) 1/86 (1.2%) 4/54 (7.4%) 5/131 (3.8%)
    Constipation 6/17 (35.3%) 3/18 (16.7%) 18/86 (20.9%) 15/54 (27.8%) 35/131 (26.7%)
    Gastrooesophageal reflux disease 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 3/54 (5.6%) 3/131 (2.3%)
    Abdominal distension 1/17 (5.9%) 2/18 (11.1%) 6/86 (7%) 6/54 (11.1%) 14/131 (10.7%)
    Auriculotemporal syndrome 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Nausea 2/17 (11.8%) 4/18 (22.2%) 22/86 (25.6%) 17/54 (31.5%) 39/131 (29.8%)
    Toothache 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 0/54 (0%) 0/131 (0%)
    Abdominal discomfort 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 3/54 (5.6%) 5/131 (3.8%)
    Gastrointestinal obstruction 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Mucous stools 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Gastritis 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 2/131 (1.5%)
    General disorders
    Pain 3/17 (17.6%) 0/18 (0%) 6/86 (7%) 6/54 (11.1%) 5/131 (3.8%)
    Chills 0/17 (0%) 1/18 (5.6%) 5/86 (5.8%) 4/54 (7.4%) 14/131 (10.7%)
    Fatigue 10/17 (58.8%) 8/18 (44.4%) 42/86 (48.8%) 31/54 (57.4%) 75/131 (57.3%)
    Infusion site extravasation 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Sensation of foreign body 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Xerosis 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Axillary pain 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 2/131 (1.5%)
    Disease progression 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Injection site discomfort 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Mucosal inflammation 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 7/131 (5.3%)
    Nodule 2/17 (11.8%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 1/131 (0.8%)
    Gait disturbance 2/17 (11.8%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 4/131 (3.1%)
    Pyrexia 3/17 (17.6%) 6/18 (33.3%) 11/86 (12.8%) 5/54 (9.3%) 26/131 (19.8%)
    Asthenia 0/17 (0%) 0/18 (0%) 6/86 (7%) 2/54 (3.7%) 10/131 (7.6%)
    Chest pain 1/17 (5.9%) 0/18 (0%) 6/86 (7%) 4/54 (7.4%) 12/131 (9.2%)
    Oedema peripheral 4/17 (23.5%) 2/18 (11.1%) 18/86 (20.9%) 9/54 (16.7%) 24/131 (18.3%)
    Influenza like illness 2/17 (11.8%) 1/18 (5.6%) 6/86 (7%) 3/54 (5.6%) 2/131 (1.5%)
    Oedema 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 2/54 (3.7%) 4/131 (3.1%)
    Chest discomfort 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 5/54 (9.3%) 10/131 (7.6%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/17 (5.9%) 2/18 (11.1%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hepatic steatosis 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Immune system disorders
    Seasonal allergy 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 0/54 (0%) 4/131 (3.1%)
    Drug hypersensitivity 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Infections and infestations
    Candidiasis 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 2/54 (3.7%) 2/131 (1.5%)
    Sinusitis 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 2/54 (3.7%) 10/131 (7.6%)
    Viral infection 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Cellulitis 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 2/54 (3.7%) 4/131 (3.1%)
    Pneumonia 0/17 (0%) 0/18 (0%) 3/86 (3.5%) 3/54 (5.6%) 5/131 (3.8%)
    Urinary tract infection 0/17 (0%) 2/18 (11.1%) 5/86 (5.8%) 4/54 (7.4%) 8/131 (6.1%)
    Fungal skin infection 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Oral herpes 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Upper respiratory tract infection 2/17 (11.8%) 5/18 (27.8%) 6/86 (7%) 3/54 (5.6%) 13/131 (9.9%)
    Nasopharyngitis 1/17 (5.9%) 1/18 (5.6%) 2/86 (2.3%) 2/54 (3.7%) 7/131 (5.3%)
    Otitis media 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Rhinitis 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Injury, poisoning and procedural complications
    Contusion 0/17 (0%) 0/18 (0%) 3/86 (3.5%) 5/54 (9.3%) 6/131 (4.6%)
    Fall 0/17 (0%) 0/18 (0%) 5/86 (5.8%) 0/54 (0%) 3/131 (2.3%)
    Infusion related reaction 0/17 (0%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 6/131 (4.6%)
    Procedural pain 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 2/131 (1.5%)
    Investigations
    Neutrophil count increased 2/17 (11.8%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Weight increased 0/17 (0%) 1/18 (5.6%) 5/86 (5.8%) 5/54 (9.3%) 5/131 (3.8%)
    Blood thyroid stimulating hormone increased 2/17 (11.8%) 1/18 (5.6%) 2/86 (2.3%) 3/54 (5.6%) 4/131 (3.1%)
    White blood cell count increased 1/17 (5.9%) 0/18 (0%) 4/86 (4.7%) 1/54 (1.9%) 1/131 (0.8%)
    Blood creatine phosphokinase increased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Blood creatinine decreased 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Blood creatinine increased 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 2/54 (3.7%) 6/131 (4.6%)
    Blood potassium decreased 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Thyroxine free increased 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Weight decreased 4/17 (23.5%) 1/18 (5.6%) 11/86 (12.8%) 10/54 (18.5%) 22/131 (16.8%)
    Blood glucose increased 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 4/131 (3.1%)
    Blood bilirubin increased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Blood lactate dehydrogenase increased 2/17 (11.8%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Granulocyte count decreased 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Prostatic specific antigen increased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Blood testosterone decreased 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    C-reactive protein increased 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    CD4 lymphocytes decreased 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 3/131 (2.3%)
    Neutrophil count decreased 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 2/131 (1.5%)
    Alanine aminotransferase increased 0/17 (0%) 1/18 (5.6%) 11/86 (12.8%) 2/54 (3.7%) 6/131 (4.6%)
    Blood alkaline phosphatase increased 1/17 (5.9%) 2/18 (11.1%) 3/86 (3.5%) 2/54 (3.7%) 6/131 (4.6%)
    Blood uric acid increased 0/17 (0%) 0/18 (0%) 3/86 (3.5%) 4/54 (7.4%) 3/131 (2.3%)
    Haemoglobin decreased 2/17 (11.8%) 3/18 (16.7%) 12/86 (14%) 7/54 (13%) 18/131 (13.7%)
    Aspartate aminotransferase increased 0/17 (0%) 1/18 (5.6%) 9/86 (10.5%) 2/54 (3.7%) 3/131 (2.3%)
    Blood phosphorus decreased 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 7/131 (5.3%)
    Thyroxine free decreased 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    White blood cell count decreased 2/17 (11.8%) 0/18 (0%) 4/86 (4.7%) 2/54 (3.7%) 5/131 (3.8%)
    Metabolism and nutrition disorders
    Hypercalcaemia 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 1/54 (1.9%) 1/131 (0.8%)
    Hypoalbuminaemia 1/17 (5.9%) 0/18 (0%) 5/86 (5.8%) 2/54 (3.7%) 2/131 (1.5%)
    Hypophosphataemia 0/17 (0%) 3/18 (16.7%) 10/86 (11.6%) 4/54 (7.4%) 7/131 (5.3%)
    Dehydration 3/17 (17.6%) 2/18 (11.1%) 6/86 (7%) 3/54 (5.6%) 12/131 (9.2%)
    Hypoglycaemia 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 1/54 (1.9%) 2/131 (1.5%)
    Diabetes mellitus 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Hyperglycaemia 5/17 (29.4%) 1/18 (5.6%) 18/86 (20.9%) 4/54 (7.4%) 10/131 (7.6%)
    Hyperuricaemia 1/17 (5.9%) 1/18 (5.6%) 7/86 (8.1%) 1/54 (1.9%) 2/131 (1.5%)
    Cachexia 1/17 (5.9%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Decreased appetite 7/17 (41.2%) 6/18 (33.3%) 31/86 (36%) 17/54 (31.5%) 46/131 (35.1%)
    Failure to thrive 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hypomagnesaemia 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 2/54 (3.7%) 4/131 (3.1%)
    Hyponatraemia 2/17 (11.8%) 2/18 (11.1%) 8/86 (9.3%) 2/54 (3.7%) 4/131 (3.1%)
    Hypokalaemia 0/17 (0%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 3/131 (2.3%)
    Hyperkalaemia 0/17 (0%) 0/18 (0%) 5/86 (5.8%) 0/54 (0%) 4/131 (3.1%)
    Iron deficiency 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 0/54 (0%) 1/131 (0.8%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 3/17 (17.6%) 0/18 (0%) 6/86 (7%) 4/54 (7.4%) 13/131 (9.9%)
    Musculoskeletal chest pain 0/17 (0%) 1/18 (5.6%) 8/86 (9.3%) 2/54 (3.7%) 9/131 (6.9%)
    Myalgia 1/17 (5.9%) 1/18 (5.6%) 9/86 (10.5%) 5/54 (9.3%) 8/131 (6.1%)
    Arthralgia 6/17 (35.3%) 5/18 (27.8%) 21/86 (24.4%) 10/54 (18.5%) 21/131 (16%)
    Musculoskeletal stiffness 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 2/54 (3.7%) 4/131 (3.1%)
    Neck pain 2/17 (11.8%) 1/18 (5.6%) 5/86 (5.8%) 3/54 (5.6%) 2/131 (1.5%)
    Pain in extremity 3/17 (17.6%) 1/18 (5.6%) 10/86 (11.6%) 7/54 (13%) 15/131 (11.5%)
    Muscle twitching 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Back pain 6/17 (35.3%) 1/18 (5.6%) 14/86 (16.3%) 12/54 (22.2%) 34/131 (26%)
    Musculoskeletal pain 1/17 (5.9%) 0/18 (0%) 11/86 (12.8%) 6/54 (11.1%) 23/131 (17.6%)
    Groin pain 3/17 (17.6%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 3/131 (2.3%)
    Muscle spasms 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 3/54 (5.6%) 14/131 (10.7%)
    Neck mass 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Pain in jaw 0/17 (0%) 1/18 (5.6%) 2/86 (2.3%) 0/54 (0%) 3/131 (2.3%)
    Sjogren's syndrome 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Dysplastic naevus 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Tumour pain 0/17 (0%) 1/18 (5.6%) 6/86 (7%) 1/54 (1.9%) 3/131 (2.3%)
    Malignant pleural effusion 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Seborrhoeic keratosis 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 0/131 (0%)
    Nervous system disorders
    Balance disorder 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 5/131 (3.8%)
    Syncope 1/17 (5.9%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Convulsion 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Headache 4/17 (23.5%) 5/18 (27.8%) 13/86 (15.1%) 12/54 (22.2%) 24/131 (18.3%)
    Mental impairment 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Peripheral sensory neuropathy 0/17 (0%) 2/18 (11.1%) 1/86 (1.2%) 1/54 (1.9%) 2/131 (1.5%)
    Tremor 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 2/54 (3.7%) 4/131 (3.1%)
    Brain oedema 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Hyperaesthesia 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Paraesthesia 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 2/54 (3.7%) 3/131 (2.3%)
    Dizziness 3/17 (17.6%) 4/18 (22.2%) 15/86 (17.4%) 9/54 (16.7%) 25/131 (19.1%)
    Neuropathy peripheral 0/17 (0%) 1/18 (5.6%) 6/86 (7%) 4/54 (7.4%) 7/131 (5.3%)
    Somnolence 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 7/131 (5.3%)
    Cerebellar haemorrhage 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Dysgeusia 2/17 (11.8%) 0/18 (0%) 6/86 (7%) 2/54 (3.7%) 13/131 (9.9%)
    Hypoaesthesia 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 5/54 (9.3%) 5/131 (3.8%)
    Sciatica 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Psychiatric disorders
    Depressed mood 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Hallucination 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Insomnia 2/17 (11.8%) 3/18 (16.7%) 10/86 (11.6%) 13/54 (24.1%) 17/131 (13%)
    Agitation 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 3/131 (2.3%)
    Anxiety 2/17 (11.8%) 0/18 (0%) 6/86 (7%) 6/54 (11.1%) 11/131 (8.4%)
    Depression 1/17 (5.9%) 1/18 (5.6%) 6/86 (7%) 5/54 (9.3%) 9/131 (6.9%)
    Confusional state 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 0/54 (0%) 9/131 (6.9%)
    Renal and urinary disorders
    Proteinuria 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 1/54 (1.9%) 1/131 (0.8%)
    Urogenital haemorrhage 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 2/131 (1.5%)
    Pollakiuria 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 2/54 (3.7%) 6/131 (4.6%)
    Haematuria 1/17 (5.9%) 1/18 (5.6%) 2/86 (2.3%) 1/54 (1.9%) 2/131 (1.5%)
    Haemorrhage urinary tract 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 0/131 (0%)
    Dysuria 2/17 (11.8%) 0/18 (0%) 1/86 (1.2%) 2/54 (3.7%) 3/131 (2.3%)
    Urinary retention 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 3/131 (2.3%)
    Reproductive system and breast disorders
    Scrotal oedema 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 1/54 (1.9%) 0/131 (0%)
    Genital erythema 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Vaginal haemorrhage 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 1/17 (5.9%) 0/18 (0%) 4/86 (4.7%) 1/54 (1.9%) 5/131 (3.8%)
    Pulmonary embolism 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Sinus congestion 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 2/54 (3.7%) 10/131 (7.6%)
    Wheezing 0/17 (0%) 0/18 (0%) 5/86 (5.8%) 4/54 (7.4%) 7/131 (5.3%)
    Upper respiratory tract congestion 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 2/54 (3.7%) 0/131 (0%)
    Pleural effusion 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 2/54 (3.7%) 9/131 (6.9%)
    Rhinitis allergic 1/17 (5.9%) 0/18 (0%) 6/86 (7%) 1/54 (1.9%) 4/131 (3.1%)
    Sneezing 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 3/131 (2.3%)
    Dry throat 2/17 (11.8%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 1/131 (0.8%)
    Dysphonia 2/17 (11.8%) 0/18 (0%) 3/86 (3.5%) 5/54 (9.3%) 9/131 (6.9%)
    Haemoptysis 0/17 (0%) 0/18 (0%) 4/86 (4.7%) 2/54 (3.7%) 10/131 (7.6%)
    Hypoxia 0/17 (0%) 0/18 (0%) 4/86 (4.7%) 5/54 (9.3%) 1/131 (0.8%)
    Rhinorrhoea 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 7/131 (5.3%)
    Lung infiltration 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 1/54 (1.9%) 0/131 (0%)
    Oropharyngeal pain 0/17 (0%) 1/18 (5.6%) 4/86 (4.7%) 5/54 (9.3%) 12/131 (9.2%)
    Respiratory tract congestion 0/17 (0%) 0/18 (0%) 2/86 (2.3%) 4/54 (7.4%) 0/131 (0%)
    Upper-airway cough syndrome 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 0/54 (0%) 6/131 (4.6%)
    Cough 6/17 (35.3%) 3/18 (16.7%) 21/86 (24.4%) 17/54 (31.5%) 42/131 (32.1%)
    Dyspnoea 0/17 (0%) 2/18 (11.1%) 22/86 (25.6%) 17/54 (31.5%) 25/131 (19.1%)
    Dyspnoea exertional 4/17 (23.5%) 2/18 (11.1%) 4/86 (4.7%) 4/54 (7.4%) 15/131 (11.5%)
    Nasal congestion 1/17 (5.9%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 7/131 (5.3%)
    Productive cough 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 6/54 (11.1%) 7/131 (5.3%)
    Throat irritation 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Skin and subcutaneous tissue disorders
    Dermatitis 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 1/131 (0.8%)
    Night sweats 2/17 (11.8%) 1/18 (5.6%) 4/86 (4.7%) 3/54 (5.6%) 8/131 (6.1%)
    Skin hyperpigmentation 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Vitiligo 3/17 (17.6%) 1/18 (5.6%) 6/86 (7%) 2/54 (3.7%) 0/131 (0%)
    Rash maculo-papular 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 0/54 (0%) 1/131 (0.8%)
    Urticaria 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 5/54 (9.3%) 2/131 (1.5%)
    Actinic keratosis 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 2/54 (3.7%) 0/131 (0%)
    Dermatitis acneiform 2/17 (11.8%) 1/18 (5.6%) 0/86 (0%) 4/54 (7.4%) 1/131 (0.8%)
    Dermatitis contact 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 1/54 (1.9%) 1/131 (0.8%)
    Hyperhidrosis 1/17 (5.9%) 0/18 (0%) 5/86 (5.8%) 3/54 (5.6%) 6/131 (4.6%)
    Melanosis 1/17 (5.9%) 0/18 (0%) 0/86 (0%) 0/54 (0%) 0/131 (0%)
    Rash 3/17 (17.6%) 5/18 (27.8%) 27/86 (31.4%) 13/54 (24.1%) 25/131 (19.1%)
    Dry skin 4/17 (23.5%) 0/18 (0%) 7/86 (8.1%) 1/54 (1.9%) 17/131 (13%)
    Facial wasting 2/17 (11.8%) 0/18 (0%) 3/86 (3.5%) 0/54 (0%) 2/131 (1.5%)
    Sunburn 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 3/54 (5.6%) 1/131 (0.8%)
    Pruritus 2/17 (11.8%) 4/18 (22.2%) 21/86 (24.4%) 8/54 (14.8%) 20/131 (15.3%)
    Erythema 0/17 (0%) 0/18 (0%) 1/86 (1.2%) 3/54 (5.6%) 8/131 (6.1%)
    Lentigo 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Rash pruritic 0/17 (0%) 1/18 (5.6%) 3/86 (3.5%) 1/54 (1.9%) 5/131 (3.8%)
    Skin lesion 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 1/54 (1.9%) 2/131 (1.5%)
    Subcutaneous nodule 1/17 (5.9%) 0/18 (0%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)
    Vascular disorders
    Deep vein thrombosis 1/17 (5.9%) 0/18 (0%) 2/86 (2.3%) 1/54 (1.9%) 1/131 (0.8%)
    Hypertension 3/17 (17.6%) 3/18 (16.7%) 6/86 (7%) 4/54 (7.4%) 6/131 (4.6%)
    Flushing 1/17 (5.9%) 1/18 (5.6%) 3/86 (3.5%) 4/54 (7.4%) 4/131 (3.1%)
    Lymphoedema 0/17 (0%) 1/18 (5.6%) 0/86 (0%) 1/54 (1.9%) 1/131 (0.8%)
    Hypotension 2/17 (11.8%) 1/18 (5.6%) 6/86 (7%) 7/54 (13%) 16/131 (12.2%)
    Orthostatic hypotension 1/17 (5.9%) 0/18 (0%) 3/86 (3.5%) 1/54 (1.9%) 2/131 (1.5%)
    Haemorrhage 0/17 (0%) 1/18 (5.6%) 1/86 (1.2%) 0/54 (0%) 0/131 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00730639
    Other Study ID Numbers:
    • CA209-003
    • MDX1106-03
    First Posted:
    Aug 8, 2008
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Nov 1, 2021