Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti–B7-H3 Antibody Drug Conjugate) Alone and in Combination with MGA012 (Anti–PD-1 Antibody) in Patients with Advanced Solid Tumors

    Summary
    EudraCT number
    		 2018-003555-38
    Trial protocol
    		 PL   ES  
    Global end of trial date
    18 Mar 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Dec 2024
    First version publication date
    07 Dec 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CP-MGC018-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03729596
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MacroGenics, Inc.
    Sponsor organisation address
    9704 Medical Center Drive, Rockville, MD, United States, 20850
    Public contact
    Global Trial Manager, MacroGenics, Inc., +1 3012515172, info@macrogenics.com
    Scientific contact
    Global Trial Manager, MacroGenics, Inc., +1 3012515172, info@macrogenics.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
    08 Dec 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Mar 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Mar 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) for MGC018 administered as monotherapy or in combination with MGA012, each administered intravenously (IV), in participants who have relapsed/refractory, unresectable locally advanced or metastatic solid tumors.
    Protection of trial subjects
    This study was conducted under United States Investigational New Drug application, in compliance with Good Clinical Practice, as well as all applicable local and national laws and regulations of countries in which the trial was performed. At each trial site, an institutional review board (IRB) or independent ethics committee (IEC) reviewed and approved the clinical trial protocol, the current and previous versions of the Investigator’s Brochure, and informed consent form(s), as applicable. The IRB/IEC subsequently approved protocol amendments and revisions. Investigators were responsible for obtaining and documenting written informed consent from each participant or legal representative. Written informed consent was obtained for all participants before any protocol-specific procedures or interventions were performed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Nov 2018
    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
    Poland: 26
    Country: Number of subjects enrolled
    Spain: 22
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    United States: 60
    Worldwide total number of subjects
    143
    EEA total number of subjects
    48
    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)
    66
    From 65 to 84 years
    76
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled from 19 investigational sites in 4 countries.

    Pre-assignment
    Screening details
    		 Adult patients with metastatic or advanced solid tumors for who no approved therapy with demonstrated clinical benefit was available.

    Period 1
    Period 1 title
    Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: 0.5 mg/kg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    vobramitamab duocarmazine
    Investigational medicinal product code
    Other name
    MGC018-01
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of 0.5 mg/kg every 3 weeks.

    Arm title
    		 Cohort 2: 1.0 mg/kg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    vobramitamab duocarmazine
    Investigational medicinal product code
    Other name
    MGC018-01
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of 1.0 mg/kg every 3 weeks.

    Arm title
    		 Cohort 3: 2.0 mg/kg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    vobramitamab duocarmazine
    Investigational medicinal product code
    Other name
    MGC018-01
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of 2.0 mg/kg every 3 weeks.

    Arm title
    		 Cohort 4: 3.0 mg/kg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    vobramitamab duocarmazine
    Investigational medicinal product code
    Other name
    MGC018-01
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of 3.0 mg/kg every 3 weeks.

    Arm title
    		 Cohort 5: 4.0 mg/kg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    vobramitamab duocarmazine
    Investigational medicinal product code
    Other name
    MGC018-01
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of 4.0 mg/kg every 3 weeks.

    Number of subjects in period 1
    		Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Started
    3
    6
    7
    121
    6
    Completed
    0
    0
    0
    0
    0
    Not completed
    3
    6
    7
    121
    6
         Consent withdrawn by subject
    -
    -
    -
    4
    1
         Death
    3
    5
    4
    95
    -
         Protocol amendment
    -
    1
    3
    6
    5
         Study terminated by sponsor
    -
    -
    -
    14
    -
         Lost to follow-up
    -
    -
    -
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: 0.5 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 2: 1.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 3: 2.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 4: 3.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 5: 4.0 mg/kg
    Reporting group description
    		 -

    Reporting group values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg Total
    Number of subjects
    		 3 6 7 121 6 143
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 4 3 54 2 66
        From 65-84 years
    		 0 2 4 66 4 76
        85 years and over
    		 0 0 0 1 0 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.3 ( 12.42 ) 56.5 ( 11.98 ) 64.0 ( 11.72 ) 62.9 ( 12.22 ) 65.3 ( 8.09 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1 4 2 40 1 48
        Male
    		 2 2 5 81 5 95
    Subject analysis sets

    Subject analysis set title
    Response Evaluable Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All participants who received at least 1 dose of study drug, had baseline measurable disease, and had at least one post-baseline radiographic tumor assessment.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants who received at least 1 dose of study drug.

    Subject analysis set title
    Metastatic prostate cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with a diagnosis of metastatic prostate cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Non-small cell lung cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of non-small lung cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Triple negative breast cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of triple negative breast cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Melanoma population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of melanoma who have received at least 1 dose of MGC018.

    Subject analysis set title
    Squamous cell carcinoma of the head and neck population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of squamous cell carcinoma of the head and neck who received at least 1 dose of MGC018.

    Subject analysis sets values
    		 Response Evaluable Population Safety population Metastatic prostate cancer population Non-small cell lung cancer population Triple negative breast cancer population Melanoma population Squamous cell carcinoma of the head and neck population
    Number of subjects
    139
    143
    41
    20
    16
    21
    13
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    63
    66
    8
    11
    14
    8
    6
        From 65-84 years
    75
    76
    33
    9
    2
    12
    7
        85 years and over
    1
    1
    0
    0
    0
    1
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    45
    48
    0
    11
    16
    5
    4
        Male
    94
    95
    41
    9
    0
    16
    9

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1: 0.5 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 2: 1.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 3: 2.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 4: 3.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 5: 4.0 mg/kg
    Reporting group description
    		 -

    Subject analysis set title
    Response Evaluable Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All participants who received at least 1 dose of study drug, had baseline measurable disease, and had at least one post-baseline radiographic tumor assessment.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants who received at least 1 dose of study drug.

    Subject analysis set title
    Metastatic prostate cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with a diagnosis of metastatic prostate cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Non-small cell lung cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of non-small lung cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Triple negative breast cancer population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of triple negative breast cancer who have received at least 1 dose of MGC018.

    Subject analysis set title
    Melanoma population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of melanoma who have received at least 1 dose of MGC018.

    Subject analysis set title
    Squamous cell carcinoma of the head and neck population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with the diagnosis of squamous cell carcinoma of the head and neck who received at least 1 dose of MGC018.

    Primary: Type and number of adverse events

    		 Close Top of page
    End point title
    		 Type and number of adverse events [1]
    End point description
    End point type
    Primary
    End point timeframe
    Adverse events are recorded from the time of informed consent signature through 30 days of the last dose of study treatment.
    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: Data displays were summary tables with the number and percent of participants who experience a given event. There is no active control or comparator to allow for statistical inferences.
    End point values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Number of subjects analysed
    3
    6
    7
    121
    6
    Units: participants with adverse events
        Study treatment related adverse event
    3
    5
    6
    120
    6
        Severe adverse event
    3
    4
    7
    105
    5
        Severe treatment related adverse event
    2
    2
    6
    79
    4
        Study treatment related serious adverse event
    1
    1
    2
    40
    2
        Fatal adverse event
    1
    0
    0
    4
    0
    No statistical analyses for this end point

    Secondary: Objective Response Rate

    		 Close Top of page
    End point title
    		 Objective Response Rate
    End point description
    The percentage of patients who have a complete or partial response to study treatment.
    End point type
    Secondary
    End point timeframe
    From the first dose of study treatment throughout the study
    End point values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg Response Evaluable Population Metastatic prostate cancer population Non-small cell lung cancer population Triple negative breast cancer population Melanoma population Squamous cell carcinoma of the head and neck population
    Number of subjects analysed
    3
    6
    7
    118
    5
    139
    Units: percentage
        number (not applicable)
    0
    0
    0
    5.9
    20
    5.8
    4.9
    15.0
    0
    4.8
    7.7
    No statistical analyses for this end point

    Secondary: Radiographic progression free survival in prostate cancer

    		 Close Top of page
    End point title
    		 Radiographic progression free survival in prostate cancer
    End point description
    End point type
    Secondary
    End point timeframe
    From the first date of study treatment until first documented disease progression or death, whichever is earlier.
    End point values
    		 Metastatic prostate cancer population
    Number of subjects analysed
    41
    Units: Months
        median (confidence interval 95%)
    5.5 (2.92 to 8.28)
    No statistical analyses for this end point

    Secondary: Prostate specific antigen response rate

    		 Close Top of page
    End point title
    		 Prostate specific antigen response rate
    End point description
    The number of patients with metastatic prostate cancer who have greater than or equal to a 50% decline in PSA, with confirmation of the decline at least 3 weeks later.
    End point type
    Secondary
    End point timeframe
    From the date of first dose throughout the study.
    End point values
    		 Metastatic prostate cancer population
    Number of subjects analysed
    41
    Units: patients with PSA response
    18
    No statistical analyses for this end point

    Secondary: Duration of PSA response

    		 Close Top of page
    End point title
    		 Duration of PSA response
    End point description
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Metastatic prostate cancer population
    Number of subjects analysed
    41
    Units: Months
        median (confidence interval 95%)
    6.2 (3.22 to 9.92)
    No statistical analyses for this end point

    Secondary: Total exposure

    		 Close Top of page
    End point title
    		 Total exposure
    End point description
    Data were obtained from 143 study subjects, with , doses of 0.5, 1, 2, 3, and 4 mg/kg were administered to, respectively, 3, 6, 8, 120, and 6 subjects
    End point type
    Secondary
    End point timeframe
    Throughout the study from baseline through treatment discontinuation.
    End point values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Number of subjects analysed
    3
    6
    7
    120
    6
    Units: mcg/mL*day
    arithmetic mean (standard deviation)
        Antibody drug conjugate
    10.6 ( 6.54 )
    51.5 ( 19.2 )
    119 ( 48.7 )
    140 ( 34.9 )
    227 ( 105 )
        Duocarmycin
    0.0448 ( 0.023 )
    0.101 ( 0.0668 )
    0.0512 ( 0.0454 )
    0.0657 ( 0.0349 )
    0.268 ( 0.061 )
    No statistical analyses for this end point

    Secondary: PK parameters: peak and trough concentrations

    		 Close Top of page
    End point title
    		 PK parameters: peak and trough concentrations
    End point description
    End point type
    Secondary
    End point timeframe
    Throughout the study from baseline through treatment discontinuation.
    End point values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Number of subjects analysed
    3
    6
    7
    121
    6
    Units: mcg/mL
    arithmetic mean (standard deviation)
        ADC maximum concentration
    7.69 ( 1.98 )
    23.4 ( 0.0408 )
    43.4 ( 14 )
    59 ( 11 )
    78.6 ( 22.4 )
        ADC trough concentration
    0.00928 ( 0.0129 )
    0.0415 ( 0.0415 )
    0.123 ( 0.652 )
    0.157 ( 0.119 )
    0.313 ( 0.323 )
        Duocarmycin maximum concentration
    0.0243 ( 0.0225 )
    0.0274 ( 0.016 )
    0.0512 ( 0.0454 )
    0.657 ( 0.0349 )
    0.0571 ( 0.00757 )
        Duocarmycin trough concentration
    0.000243 ( 0.000107 )
    0.00074 ( 0.000532 )
    0.00226 ( 0.00244 )
    0.00185 ( 0.000658 )
    0.00194 ( 0.000973 )
    No statistical analyses for this end point

    Secondary: Duration of Response

    		 Close Top of page
    End point title
    		 Duration of Response
    End point description
    End point type
    Secondary
    End point timeframe
    The time from the first documented complete or partial response to the first documented disease progression or death, whichever comes first.
    End point values
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg Metastatic prostate cancer population Non-small cell lung cancer population Triple negative breast cancer population Melanoma population Squamous cell carcinoma of the head and neck population
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    7
    1
    41
    20
    0 [5]
    21
    13
    Units: Months
    number (not applicable)
        Minimum duration
    1.41
    5.32
    4.27
    1.14
    10.28
    2.10
        Maximum duration
    17.61
    5.32
    6.28
    17.61
    10.28
    2.10
    Notes
    [2] - There were no responses in this group.
    [3] - There were no responses in this group.
    [4] - There were no responses in this group.
    [5] - There were no clinical responses in this group.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected from the time of first dose through 30 days after the last dose, average 6 months. All-cause mortality was collected from the first dose until the primary completion date, average 2 years.
    Adverse event reporting additional description
    AEs are based on physical exam, patient reports, and significant abnormal laboratory values. AEs were not collected in survival follow up. Only SAEs were collected in survival follow up if related to study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25
    Reporting groups
    Reporting group title
    Cohort 1: 0.5 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 2: 1.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 3: 2.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 4: 3.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 5: 4.0 mg/kg
    Reporting group description
    		 -

    Serious adverse events
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 7 (42.86%)
    52 / 121 (42.98%)
    2 / 6 (33.33%)
         number of deaths (all causes)
    3
    5
    4
    95
    0
         number of deaths resulting from adverse events
    1
    0
    0
    4
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    4 / 121 (3.31%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Face oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    5 / 121 (4.13%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    4 / 121 (3.31%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Angina pectoris
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Lethargy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    5 / 121 (4.13%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    4 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    3 / 121 (2.48%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Pancytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    4 / 121 (3.31%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    3 / 121 (2.48%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Duodenal ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Enterovesical fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    0 / 121 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 121 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    3 / 121 (2.48%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematinuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 121 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis pasteurella
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 121 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    3 / 121 (2.48%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    2 / 121 (1.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Catheter site infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Clostridium difficile infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Coronavirus infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 121 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Herpes simplex
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia aspiration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Subdural haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 121 (0.83%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: 0.5 mg/kg Cohort 2: 1.0 mg/kg Cohort 3: 2.0 mg/kg Cohort 4: 3.0 mg/kg Cohort 5: 4.0 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    7 / 7 (100.00%)
    121 / 121 (100.00%)
    6 / 6 (100.00%)
    General disorders and administration site conditions
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    2 / 7 (28.57%)
    42 / 121 (34.71%)
    3 / 6 (50.00%)
         occurrences all number
    0
    4
    2
    50
    4
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    20 / 121 (16.53%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    30
    0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    7 / 121 (5.79%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    0
    7
    2
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    2 / 7 (28.57%)
    61 / 121 (50.41%)
    3 / 6 (50.00%)
         occurrences all number
    1
    2
    2
    75
    4
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    9 / 121 (7.44%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    9
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    35 / 121 (28.93%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    47
    0
    Pyrexia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    2 / 7 (28.57%)
    12 / 121 (9.92%)
    4 / 6 (66.67%)
         occurrences all number
    1
    0
    2
    12
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    17 / 121 (14.05%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    17
    0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    25 / 121 (20.66%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    1
    25
    3
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    35 / 121 (28.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    38
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    9 / 121 (7.44%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    11
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 7 (28.57%)
    17 / 121 (14.05%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    22
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    25 / 121 (20.66%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    3
    44
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    16 / 121 (13.22%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    22
    1
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    19 / 121 (15.70%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    19
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    16 / 121 (13.22%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    18
    2
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 7 (28.57%)
    17 / 121 (14.05%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    3
    29
    2
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    6 / 121 (4.96%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    9
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    15 / 121 (12.40%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    15
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    8 / 121 (6.61%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    8
    0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    25 / 121 (20.66%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    29
    1
    Neuropathy peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    8 / 121 (6.61%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    10
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 7 (28.57%)
    37 / 121 (30.58%)
    2 / 6 (33.33%)
         occurrences all number
    1
    1
    2
    48
    2
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 7 (28.57%)
    43 / 121 (35.54%)
    3 / 6 (50.00%)
         occurrences all number
    0
    1
    2
    69
    3
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    17 / 121 (14.05%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    25
    1
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    8 / 121 (6.61%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    10
    2
    Lymphopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    9 / 121 (7.44%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    9
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    12 / 121 (9.92%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    13
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 7 (0.00%)
    6 / 121 (4.96%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    7
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 7 (14.29%)
    5 / 121 (4.13%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    6
    0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    22 / 121 (18.18%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    22
    1
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    17 / 121 (14.05%)
    3 / 6 (50.00%)
         occurrences all number
    0
    1
    1
    21
    3
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    8 / 121 (6.61%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    12
    0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    19 / 121 (15.70%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    21
    1
    Vomiting
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    2 / 7 (28.57%)
    19 / 121 (15.70%)
    0 / 6 (0.00%)
         occurrences all number
    1
    4
    2
    22
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    12 / 121 (9.92%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    12
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    3 / 7 (42.86%)
    50 / 121 (41.32%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    3
    64
    2
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 7 (14.29%)
    19 / 121 (15.70%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    25
    0
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    20 / 121 (16.53%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    22
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    1 / 7 (14.29%)
    28 / 121 (23.14%)
    2 / 6 (33.33%)
         occurrences all number
    0
    3
    1
    28
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    9 / 121 (7.44%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    10
    1
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    10 / 121 (8.26%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    11
    0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    8 / 121 (6.61%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    8
    3
    Pain in extremity
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    6 / 121 (4.96%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    8
    0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    10 / 121 (8.26%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    12
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    8 / 121 (6.61%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    9
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    40 / 121 (33.06%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    1
    44
    1
    Dehydration
         subjects affected / exposed
    2 / 3 (66.67%)
    3 / 6 (50.00%)
    0 / 7 (0.00%)
    5 / 121 (4.13%)
    1 / 6 (16.67%)
         occurrences all number
    3
    3
    0
    6
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    7 / 121 (5.79%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    9
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Oct 2018
    Added safety measures: sentinel dosing for first 2 dose levels, Independent Safety Monitor oversight, revised definition of non-hematologic dose limiting toxicity, revised inclusion criteria, added cardiac monitoring, added ophthalmological examinations, and amylase and lipase monitoring.
    26 Feb 2019
    Modified entry criteria to require metastatic castration-resistant prostate cancer, and PSA testing for all participants with prostate cancer.
    31 Jul 2020
    Added tumor types to expansion cohorts: metastatic castration-resistant prostate cancer, non-small cell lung cancer, and triple negative breast cancer. Relevant sections of the protocol were updated accordingly, including study design, sample size, objectives, eligibility, and medical history requirements. Added secondary objectives to describe the radiographic progression free survival, PSA response rate and best PSA percent change from baseline. Added exploratory objective for patient reported outcome using the brief pain inventory short form and symptomatic skeletal events . Provided guidance of study procedures during the COVID-19 pandemic. Revised toxicity management guidelines.
    17 Mar 2021
    Updated the study design to include additional expansion cohorts of squamous cell cancer of the head and neck and melanoma. Relevant sections of the protocol were updated accordingly, including study design, sample size, objectives, eligibility, and medical history requirements. Updated toxicity management guidelines
    26 Jul 2021
    Revised toxicity management guidelines.
    16 Aug 2021
    Revised toxicity management guidelines.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 31 10:59:45 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA