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    Clinical Trial Results:
    A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Subjects with Select Advanced Malignancies

    Summary
    EudraCT number
    2016-000323-43
    Trial protocol
    GB   NL  
    Global end of trial date
    17 Mar 2020

    Results information
    Results version number
    v2(current)
    This version publication date
    26 May 2021
    First version publication date
    20 Mar 2021
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    D6020C00001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02118337
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, United States, 20878
    Public contact
    Farzana Walcott, MedImmune, LLC, +1 3013983063, information.center@astrazeneca.com
    Scientific contact
    Farzana Walcott, MedImmune, LLC, +1 3013983063, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Oct 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Mar 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of the study are as below: 1. For dose-escalation phase: To determine safety profile of of MEDI0680 in combination with durvalumab in participants with select advanced malignancies. 2. For dose-expansion: To evaluate the antitumor activity of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy naïve participants with advanced or metastatic clear cell renal cell carcinoma (ccRCC) as based on investigator assessed response using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    19 May 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 66
    Worldwide total number of subjects
    97
    EEA total number of subjects
    16
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    56
    From 65 to 84 years
    40
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    The study is conducted in Australia, Canada, France, Netherlands, United Kingdom, and the United States.

    Pre-assignment
    Screening details
    Of the 130 participants screened, 97 participants were enrolled and were treated in this study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of MEDI0680 0.1 mg/kg Q2W for up to 12 months.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 3 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 0.1 mg/kg + Durvalumab 10 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 0.1 mg/kg Q2W for up to 12 months.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 10 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 0.5 mg/kg + Durvalumab 10 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 0.5 mg/kg Q2W for up to 12 months.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 10 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 2.5 mg/kg + Durvalumab 10 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 2.5 mg/kg Q2W for up to 12 months.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 10 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 10 mg/kg + Durvalumab 10 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 10 mg/kg Q2W for up to 12 months.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 10 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm description
    Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 20 mg/kg Q2W for up to 12 months

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 10 mg Q2W for up to 12 months.

    Arm title
    MEDI0680 20 mg/kg
    Arm description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Arm title
    MEDI0680 20 mg/kg + Durvalumab 750 mg
    Arm description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI0680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of durvalumab 750 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Arm title
    Nivolumab 240 mg
    Arm description
    Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of nivolumab 240 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Number of subjects in period 1
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Started
    4
    5
    3
    3
    9
    6
    4
    42
    21
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    4
    5
    3
    3
    9
    6
    4
    42
    21
         Consent withdrawn by subject
    1
    3
    2
    1
    2
    2
    1
    4
    2
         Death
    2
    2
    1
    2
    5
    1
    2
    9
    4
         Unspecified
    1
    -
    -
    -
    2
    3
    1
    28
    15
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

    Reporting group title
    MEDI0680 0.1 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 0.5 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 2.5 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 10 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 20 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 20 mg/kg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Reporting group title
    MEDI0680 20 mg/kg + Durvalumab 750 mg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Reporting group title
    Nivolumab 240 mg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Reporting group values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg Total
    Number of subjects
    4 5 3 3 9 6 4 42 21 97
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    2 2 2 2 7 1 2 21 17 56
        From 65-84 years
    2 3 1 1 1 5 2 21 4 40
        85 years and over
    0 0 0 0 1 0 0 0 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    60.5 ± 12.6 67.4 ± 8.4 52.3 ± 17.9 62.3 ± 11.6 62.1 ± 11.0 69.5 ± 9.9 64.8 ± 14.2 61.0 ± 9.8 59.1 ± 10.5 -
    Sex: Female, Male
    Units: Participants
        Female
    1 3 1 1 5 2 1 9 6 29
        Male
    3 2 2 2 4 4 3 33 15 68
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0 0 1 0 0 1
        Asian
    0 1 0 0 0 0 0 1 0 2
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 1 0 0 0 0 1
        Black or African American
    0 0 0 0 0 0 0 0 3 3
        White
    4 4 3 2 8 6 3 34 16 80
        More than one race
    0 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    0 0 0 1 0 0 0 7 2 10
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 0 1 0 2 0 0 1 1 6
        Not Hispanic or Latino
    3 5 2 2 7 6 4 40 20 89
        Unknown or Not Reported
    0 0 0 1 0 0 0 1 0 2

    End points

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    End points reporting groups
    Reporting group title
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

    Reporting group title
    MEDI0680 0.1 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 0.5 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 2.5 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 10 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 20 mg/kg + Durvalumab 10 mg
    Reporting group description
    Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Reporting group title
    MEDI0680 20 mg/kg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Reporting group title
    MEDI0680 20 mg/kg + Durvalumab 750 mg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Reporting group title
    Nivolumab 240 mg
    Reporting group description
    Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase

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    End point title
    Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase [1] [2]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Primary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Participants
        Any TEAE
    4
    5
    3
    3
    9
    6
        Any TESAE
    1
    1
    1
    2
    6
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase

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    End point title
    Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase [3] [4]
    End point description
    Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Primary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Participants
        Anaemia
    0
    0
    1
    1
    3
    0
        Iron deficiency anaemia
    0
    0
    0
    0
    1
    0
        Leukocytosis
    1
    0
    0
    0
    0
    0
        Lymphopenia
    0
    0
    0
    0
    1
    0
        Activated partial thromboplastin time prolonged
    0
    0
    0
    0
    0
    1
        Blood fibrinogen decreased
    1
    0
    0
    0
    0
    1
        International normalized ratio
    0
    0
    0
    0
    0
    1
        Lymphocyte count decreased
    0
    0
    0
    0
    0
    1
        Prothrombin time prolonged
    0
    0
    0
    0
    0
    1
        White blood cell count decreased
    0
    0
    0
    0
    0
    1
        Alanine aminotransferase increased
    0
    0
    0
    0
    1
    0
        Amylase increased
    0
    0
    0
    0
    1
    1
        Aspartate aminotransferase increased
    0
    0
    0
    0
    2
    0
        Blood alkaline phosphatase increased
    1
    0
    1
    0
    1
    0
        Blood creatinine increased
    0
    0
    0
    0
    2
    1
        Blood phosphorus decreased
    1
    0
    0
    0
    0
    0
        Blood urea increased
    0
    0
    0
    0
    1
    0
        Gamma glutamyltransferase increased
    0
    0
    0
    0
    1
    0
        Lipase increased
    1
    0
    1
    0
    1
    0
        Hypercalcaemia
    0
    0
    0
    0
    1
    1
        Hyperglycaemia
    0
    0
    0
    0
    1
    0
        Hyperkalaemia
    0
    0
    0
    0
    1
    0
        Hypermagnesaemia
    0
    0
    1
    0
    0
    0
        Hyperuricaemia
    1
    0
    0
    0
    1
    0
        Hypoalbuminaemia
    0
    0
    0
    0
    1
    0
        Hypokalaemia
    0
    0
    0
    0
    2
    0
        Hypomagnesaemia
    0
    0
    0
    0
    2
    0
        Hyponatraemia
    0
    0
    0
    0
    2
    1
        proteinuria
    0
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase

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    End point title
    Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase [5] [6]
    End point description
    Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Primary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Participants
        Atrial fibrillation
    0
    0
    0
    0
    1
    0
        Palpitations
    1
    0
    0
    0
    0
    0
        Sinus tachycardia
    0
    0
    0
    0
    1
    0
        Tachycardia
    0
    0
    0
    0
    0
    1
        Pyrexia
    0
    0
    2
    0
    3
    1
        Weight decreased
    0
    0
    0
    0
    1
    1
        Hypertension
    1
    0
    0
    0
    1
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase

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    End point title
    Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase [7] [8]
    End point description
    Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Primary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Participants
        Palpitations
    1
    0
    0
    0
    0
    0
        Atrial fibrillation
    0
    0
    0
    0
    1
    0
        Sinus tachycardia
    0
    0
    0
    0
    1
    0
        Pericardial effusion
    0
    0
    0
    0
    1
    0
        Tachycardia
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase

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    End point title
    Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase [9]
    End point description
    The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. As-treated population was analysed for this end point.
    End point type
    Primary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0 to 60.2)
    16.7 (7.0 to 31.4)
    23.8 (8.2 to 47.2)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    MEDI0680 20 mg/kg v Nivolumab 240 mg
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.5494
    Method
    Fisher exact
    Parameter type
    Rate difference
    Point estimate
    -23.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -72.8
         upper limit
    31.1
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    MEDI0680 20 mg/kg + Durvalumab 750 mg v Nivolumab 240 mg
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.513
    Method
    Fisher exact
    Parameter type
    Rate difference
    Point estimate
    -7.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.6
         upper limit
    20

    Secondary: Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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    End point title
    Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [10]
    End point description
    The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Participants
        CR
    0
    2
    0
        PR
    0
    5
    5
        SD
    3
    17
    8
        PD
    1
    17
    6
        NE
    0
    1
    2
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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    End point title
    Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [11]
    End point description
    The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The DCR at >= 8 weeks and >=24 weeks are reported. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Percentage of participants
    number (confidence interval 95%)
        DCR at >=8 weeks
    75.0 (19.4 to 99.4)
    57.1 (41.0 to 72.3)
    61.9 (38.4 to 81.9)
        DCR at >=24 weeks
    50.0 (6.8 to 93.2)
    38.1 (23.6 to 54.4)
    38.1 (18.1 to 61.6)
    No statistical analyses for this end point

    Secondary: Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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    End point title
    Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [12]
    End point description
    The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. The TTR was analysed for participants from As-treated population who achieved OR.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    0 [13]
    7
    5
    Units: Months
        median (confidence interval 95%)
    ( to )
    1.8 (1.7 to 9.1)
    1.8 (1.6 to 7.3)
    Notes
    [13] - No participant had achieved OR.
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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    End point title
    Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [14]
    End point description
    The DoR is defined as duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The confirmed CR or confirmed PR means 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs ((>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between; and PD means at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method. The arbitrary numbers 99.999 and 99999 signified the data for median and upper limit of confidence interval could not be derived due to insufficient events being observed at the time of the analysis. The DoR was analysed for participants from As-treated population who achieved OR.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    0 [15]
    7
    5
    Units: Months
        median (confidence interval 95%)
    ( to )
    99.999 (12.9 to 99999)
    99.999 (4.4 to 99999)
    Notes
    [15] - No participant had achieved OR in this arm.
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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    End point title
    Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [16]
    End point description
    The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Months
        median (confidence interval 95%)
    5.5 (2.2 to 7.4)
    3.6 (2.0 to 5.5)
    3.6 (1.9 to 13.0)
    No statistical analyses for this end point

    Secondary: Overall Survival in Dose-expansion Phase

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    End point title
    Overall Survival in Dose-expansion Phase [17]
    End point description
    The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary numbers 99.999, 0.9999, and 99999 signified the data for median, and lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Months
        median (confidence interval 95%)
    19.9 (7.0 to 19.9)
    99.999 (0.9999 to 99999)
    99.999 (12.0 to 99999)
    No statistical analyses for this end point

    Secondary: BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [18]
    End point description
    The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Participants
        CR
    0
    0
    0
    0
    1
    0
        PR
    2
    0
    1
    0
    3
    4
        SD
    1
    1
    0
    1
    2
    1
        PD
    1
    3
    2
    1
    2
    1
        NE
    0
    1
    0
    1
    1
    0
    No statistical analyses for this end point

    Secondary: ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [19]
    End point description
    The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Percentage of participants
        number (confidence interval 95%)
    50.0 (6.8 to 93.2)
    0 (0 to 52.2)
    33.3 (0.8 to 90.6)
    0 (0 to 70.8)
    44.4 (13.7 to 78.8)
    66.7 (22.3 to 95.7)
    No statistical analyses for this end point

    Secondary: DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [20]
    End point description
    The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The DCR at >= 8 weeks and >=24 weeks are reported. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Percentage of participants
    number (confidence interval 95%)
        DCR at >= 8 weeks
    75.0 (19.4 to 99.4)
    20.0 (0.5 to 71.6)
    33.3 (0.8 to 90.6)
    33.3 (0.8 to 90.6)
    66.7 (29.9 to 92.5)
    83.3 (35.9 to 99.6)
        DCR at >= 24 weeks
    50.0 (6.8 to 93.2)
    0 (0 to 52.2)
    33.3 (0.8 to 90.6)
    0 (0 to 70.8)
    44.4 (13.7 to 78.8)
    83.3 (35.9 to 99.6)
    No statistical analyses for this end point

    Secondary: TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [21]
    End point description
    The TTR is defined as time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified RECIST v1.1. Confirmed CR or confirmed PR are defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. As-treated population was analysed for this end point. The arbitrary numbers 0.9999 and 99999 signified the data for lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The TTR was analysed for participants from As-treated population who achieved OR.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    2
    0 [22]
    1
    0 [23]
    4
    4
    Units: Months
        median (confidence interval 95%)
    2.6 (1.6 to 3.5)
    ( to )
    3.4 (0.9999 to 99999)
    ( to )
    3.5 (1.6 to 3.5)
    3.2 (1.7 to 10.8)
    Notes
    [22] - No participant had achieved OR.
    [23] - No participant had achieved OR.
    No statistical analyses for this end point

    Secondary: DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [24]
    End point description
    The DoR is defined as duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. Confirmed CR or confirmed PR are defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs ((>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The arbitrary numbers 99.999, 0.9999, and 99999 signified data for median, and lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The DoR was analysed for participants from As-treated population who achieved OR.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    2
    0 [25]
    1
    0 [26]
    4
    4
    Units: Months
        median (confidence interval 95%)
    16.8 (0.9999 to 99999)
    ( to )
    99.999 (0.9999 to 99999)
    ( to )
    7.4 (5.6 to 99999)
    99.999 (5.6 to 99999)
    Notes
    [25] - No participant had achieved OR.
    [26] - No participant had achieved OR.
    No statistical analyses for this end point

    Secondary: PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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    End point title
    PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [27]
    End point description
    The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The arbitrary number 99999 signified the data for upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The PFS was estimated using Kaplan-Meier method. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Months
        median (confidence interval 95%)
    20.2 (1.6 to 20.2)
    1.7 (1.6 to 3.5)
    1.6 (1.6 to 99999)
    1.8 (1.5 to 3.4)
    7.0 (1.6 to 99999)
    23.4 (1.8 to 99999)
    No statistical analyses for this end point

    Secondary: OS in Dose-escalation Phase

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    End point title
    OS in Dose-escalation Phase [28]
    End point description
    The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary numbers 99.999, 0.9999, and 99999 signified the data for median, and lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. As-treated population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    Units: Months
        median (confidence interval 95%)
    16.3 (3.6 to 99999)
    99.999 (4.2 to 99999)
    14.7 (0.9999 to 99999)
    7.9 (1.5 to 7.9)
    12.8 (3.1 to 99999)
    99.999 (29.6 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs and TESAEs in Dose-expansion Phase

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    End point title
    Number of Participants With TEAEs and TESAEs in Dose-expansion Phase [29]
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Participants
        Any TEAE
    4
    42
    20
        Any TESAE
    3
    22
    13
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase

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    End point title
    Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase [30]
    End point description
    Number of participants in dose-expansion phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Participants
        Anaemia
    1
    6
    5
        Neutropenia
    0
    1
    0
        Blood iron decreased
    0
    0
    1
        Lymphocyte count decreased
    0
    0
    1
        Neutrophil count decreased
    1
    1
    0
        Platelet count decreased
    0
    0
    1
        Platelet count increased
    0
    0
    1
        Prothrombin time prolonged
    0
    0
    1
        White blood cell count increased
    0
    0
    1
        Alanine aminotransferase increased
    1
    1
    3
        Amylase decreased
    0
    0
    1
        Amylase increased
    1
    3
    3
        Aspartate aminotransferase increased
    1
    2
    3
        Blood alkaline phosphatase increased
    0
    0
    1
        Blood bilirubin increased
    0
    0
    1
        Blood creatine increased
    1
    1
    0
        Blood creatine phosphokinase increased
    0
    1
    0
        Blood creatinine increased
    1
    4
    3
        Blood glucose increased
    0
    0
    1
        Blood triglycerides increased
    0
    1
    1
        C-reactive protein increased
    0
    1
    1
        Lipase increased
    1
    4
    2
        Transaminases increased
    0
    1
    0
        Hypercalcaemia
    0
    6
    2
        Hyperglycaemia
    0
    1
    0
        Hyperkalaemia
    0
    2
    2
        Hypertriglyceridaemia
    0
    1
    0
        Hypoalbuminaemia
    0
    2
    0
        Hypocalcaemia
    0
    1
    0
        Hypoglycaemia
    0
    1
    0
        Hypokalaemia
    0
    5
    2
        Hypomagnesaemia
    0
    4
    2
        Hyponatraemia
    1
    3
    1
        Hypophosphataemia
    0
    1
    3
        Urine abnormality
    0
    1
    0
        Blood thyroid stimulating hormone increased
    0
    2
    2
        Blood urine present
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase

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    End point title
    Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase [31]
    End point description
    Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Participants
        Atrial fibrillation
    0
    2
    1
        Tachycardia
    0
    1
    0
        Pyrexia
    2
    9
    2
        Weight decreased
    0
    5
    0
        Weight increased
    0
    3
    0
        Hypoxia
    0
    1
    1
        Hypertension
    1
    5
    0
        Hypotension
    1
    2
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase

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    End point title
    Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase [32]
    End point description
    Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Participants
        Angina pectoris
    1
    1
    0
        Tachycardia
    0
    1
    0
        Atrial fibrillation
    0
    2
    1
        Cardiac failure congestive
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases

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    End point title
    Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases [33]
    End point description
    Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. Participants from As-treated population who received MEDI0680, grouped according to actual treatment received, and had quantifiable and calculable serum samples at the specified time points were analysed for this end point. The arbitrary number 9999.9 signified the sample was not quantifiable and therefore, not calculable. The arbitrary number 0.0009 signified no data as no participants were analysed for the specified time points. Here, 'n' denotes the number of participants analysed at the specified time points.
    End point type
    Secondary
    End point timeframe
    Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    4
    40
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cmin at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 4, 40)
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
        Cmax at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 4, 4, 38)
    4.330 ± 26.18
    3.877 ± 54.68
    16.36 ± 26.46
    69.28 ± 24.76
    272.4 ± 24.62
    529.9 ± 29.84
    668.8 ± 21.04
    135.9 ± 4007
        Cmin at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 5, 0, 0)
    1.143 ± 22.70
    0.9937 ± 35.93
    4.428 ± 62.38
    18.67 ± 12.88
    46.87 ± 559.4
    205.8 ± 24.56
    0.0009 ± 0.0009
    0.0009 ± 0.0009
        Cmax at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 5, 0, 0)
    5.420 ± 21.61
    3.835 ± 25.30
    20.52 ± 26.26
    87.78 ± 20.69
    348.1 ± 27.78
    716.8 ± 26.72
    0.0009 ± 0.0009
    0.0009 ± 0.0009
        Cmin at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 4, 36)
    1.645 ± 49.08
    1.361 ± 38.07
    7.879 ± 52.74
    31.81 ± 4.480
    155.7 ± 24.20
    378.0 ± 17.95
    308.6 ± 30.45
    253.9 ± 52.11
        Cmax at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 4, 34)
    3.515 ± 145.9
    3.688 ± 80.17
    17.28 ± 56.32
    92.07 ± 17.72
    440.7 ± 28.18
    860.8 ± 13.82
    936.1 ± 24.91
    586.6 ± 63.42
    No statistical analyses for this end point

    Secondary: Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases

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    End point title
    Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases [34]
    End point description
    Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. Participants from As-treated population who received durvalumab, grouped according to actual treatment received, and had quantifiable and calculable serum samples at the specified time points were analysed for this end point. The arbitrary number 9999.9 signified the sample was not quantifiable and therefore, not calculable. The arbitrary number 0.0009 signified no data as no participants were analysed for the specified time points. Here, 'n' denotes the number of participants analysed at the specified time points.
    End point type
    Secondary
    End point timeframe
    Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Number of subjects analysed
    4
    5
    3
    3
    9
    6
    41
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cmin at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 38)
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
    9999.9 ± 9999.9
        Cmax at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 41)
    65.47 ± 10.02
    216.1 ± 25.14
    213.8 ± 9.943
    188.0 ± 17.82
    248.0 ± 27.20
    253.9 ± 11.35
    186.9 ± 33.42
        Cmin at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 6, 0)
    19.62 ± 16.49
    63.02 ± 7.836
    49.04 ± 80.97
    86.10 ± 69.76
    79.59 ± 63.46
    70.31 ± 22.00
    0.0009 ± 0.0009
        Cmax at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 6, 0)
    95.14 ± 12.79
    245.8 ± 13.45
    241.1 ± 30.90
    225.0 ± 9.213
    292.7 ± 33.84
    321.8 ± 23.05
    0.0009 ± 0.0009
        Cmin at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 27)
    23.83 ± 14.35
    83.76 ± 34.29
    89.20 ± 56.00
    136.3 ± 45.72
    124.8 ± 55.78
    142.5 ± 50.52
    78.41 ± 55.62
        Cmax at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 32)
    84.43 ± 17.13
    280.9 ± 12.48
    297.5 ± 42.41
    267.0 ± 25.97
    370.9 ± 42.57
    342.3 ± 18.08
    258.1 ± 28.36
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases

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    End point title
    Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases [35]
    End point description
    Number of participants with positive ADAs to MEDI0680 are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). As-treated population (participants who received MEDI0680 and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Number of subjects analysed
    4
    5
    3
    3
    8
    6
    4
    39
    Units: Participants
        ADA positive post-baseline
    2
    0
    2
    0
    0
    0
    0
    2
        Persistent Positive
    2
    0
    2
    0
    0
    0
    0
    0
        Transient Positive
    0
    0
    0
    0
    0
    0
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases

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    End point title
    Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases [36]
    End point description
    Number of participants with positive ADA to durvalumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). As-treated population (participants who received durvalumab and grouped according to actual treatment received) was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Number of subjects analysed
    4
    5
    3
    3
    8
    6
    39
    Units: Participants
        ADA positive post-baseline
    1
    0
    0
    0
    0
    0
    2
        Persistent Positive
    1
    0
    0
    0
    0
    0
    2
        Transient Positive
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase

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    End point title
    ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase [37]
    End point description
    ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. Participants from As-treated population with PD-L1 positive (> 1% tumor cell membrane or > 1% immune cell staining) and PD-L1 negative (<= 1% tumor cell membrane and <= 1% immune cell staining) were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Number of subjects analysed
    4
    42
    21
    Units: Percentage of Participants
    number (confidence interval 95%)
        Participants with PD-L1 positive
    0 (0 to 97.5)
    40.0 (5.3 to 85.3)
    37.5 (8.5 to 75.5)
        Participants with PD-L1 negative
    0 (0 to 70.8)
    13.5 (4.5 to 28.8)
    15.4 (1.9 to 45.4)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 20 mg/kg Q2W
    Reporting group description
    -

    Reporting group title
    MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W
    Reporting group description
    -

    Reporting group title
    Nivolumab 240mg Q2W
    Reporting group description
    -

    Serious adverse events
    MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 20 mg/kg Q2W MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W Nivolumab 240mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    6 / 9 (66.67%)
    0 / 6 (0.00%)
    3 / 4 (75.00%)
    22 / 42 (52.38%)
    13 / 21 (61.90%)
         number of deaths (all causes)
    2
    2
    1
    2
    5
    1
    2
    9
    4
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to bone
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eye pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    2 / 21 (9.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated enterocolitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated pancreatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash papular
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia of malignancy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    3 / 21 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W MEDI0680 20 mg/kg Q2W MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W Nivolumab 240mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    5 / 5 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    9 / 9 (100.00%)
    6 / 6 (100.00%)
    4 / 4 (100.00%)
    41 / 42 (97.62%)
    20 / 21 (95.24%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Tumour pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Aortic occlusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Flushing
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    1
    0
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Hypertension
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    5 / 42 (11.90%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    3
    1
    7
    0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    1
    Vena cava embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    5 / 42 (11.90%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    7
    1
    Axillary pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Catheter site pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    0
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    3 / 42 (7.14%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    2
    Cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Facial pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 5 (60.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
    4 / 4 (100.00%)
    19 / 42 (45.24%)
    6 / 21 (28.57%)
         occurrences all number
    2
    3
    1
    1
    2
    3
    4
    25
    7
    Feeling hot
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gait disturbance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    2
    Inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    1
    Infusion site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Malaise
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    2
    1
    Nodule
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    Oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 42 (2.38%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    2
    Oedema peripheral
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    5 / 42 (11.90%)
    3 / 21 (14.29%)
         occurrences all number
    2
    0
    1
    0
    5
    0
    1
    7
    4
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    3 / 42 (7.14%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    3 / 9 (33.33%)
    1 / 6 (16.67%)
    2 / 4 (50.00%)
    8 / 42 (19.05%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    0
    3
    1
    2
    12
    3
    Secretion discharge
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Temperature intolerance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Contrast media reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Galactorrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Pruritus genital
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    5
    0
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    9 / 42 (21.43%)
    8 / 21 (38.10%)
         occurrences all number
    0
    1
    1
    0
    1
    4
    2
    17
    9
    Dry throat
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dysphonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Dyspnoea
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    7 / 42 (16.67%)
    8 / 21 (38.10%)
         occurrences all number
    1
    1
    0
    0
    3
    0
    0
    9
    10
    Dyspnoea exertional
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    3
    3
    Haemoptysis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Laryngeal obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Lung disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Nasal congestion
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    2 / 21 (9.52%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    3
    2
    Oropharyngeal discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    2
    2
    Painful respiration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Paranasal sinus hypersecretion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    1
    Pneumonitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    3
    Productive cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    7 / 42 (16.67%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    8
    2
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rales
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    4 / 42 (9.52%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    7
    4
    Sinus congestion
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    2 / 42 (4.76%)
    2 / 21 (9.52%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    2
    2
    Confusional state
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Delirium
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Insomnia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    5 / 42 (11.90%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    5
    3
    Mood altered
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 42 (2.38%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    0
    5
    0
    1
    3
    3
    Amylase decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Amylase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    3 / 42 (7.14%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    6
    8
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    2 / 42 (4.76%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    1
    14
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    3
    0
    1
    0
    1
    0
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood creatine increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    4 / 42 (9.52%)
    3 / 21 (14.29%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    1
    5
    6
    Blood fibrinogen decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood iron decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Blood testosterone decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood thyroid stimulating hormone increased