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    Clinical Trial Results:
    First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of GEN1044 in subjects with malignant solid tumors

    Summary
    EudraCT number
    		 2019-003998-26
    Trial protocol
    		 DK   ES  
    Global end of trial date
    29 Oct 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Nov 2022
    First version publication date
    01 Nov 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GCT1044-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04424641
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Genmab
    Sponsor organisation address
    Kalvebod Brygge 43, Copenhagen V, Denmark, 1560
    Public contact
    Clinical Trial Information, Genmab, +45 7020 2728, clinicaltrials@genmab.com
    Scientific contact
    Clinical Trial Information, Genmab, +45 7020 2728, clinicaltrials@genmab.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
    24 May 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Oct 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of the study for dose-escalation part was to determine recommended phase 2 dose (RP2D) and to establish safety profile of GEN1044, and for expansion part it was to evaluate anti-tumor activity of GEN1044.
    Protection of trial subjects
    The trial was conducted in accordance with the protocol and amendments, the International Council for Harmonisation E6 guideline for Good Clinical Practice, applicable local regulations, and ethical principles that have their origins in the Declaration of Helsinki. In addition, the trial was conducted in accordance with FDA 21 Code of Federal Regulations parts 312, 50, and 56, and the directive 2001/20/EC of the European Parliament.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jul 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    United States: 11
    Worldwide total number of subjects
    37
    EEA total number of subjects
    23
    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)
    27
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 48 participants signed the informed consent form of whom 37 received study drug. The Safety Committee decided to stop enrollment during the dose-escalation part and therefore the expansion part of trial never started. Consequently, results are only available for the dose-escalation part.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GEN1044 Doses 0.3/3/3 mg
    Arm description
    		 Participants with locally advanced or metastatic non-central nervous system (non-CNS) solid tumor(s) received intravenous (IV) infusion of GEN1044 weekly (0.3 mg on Cycle [C] 1 Day (D] 1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by every 3 weeks (Q3W) until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (0.3 mg on C1D1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by every 3 weeks (Q3W) until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/3/10 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/3/30 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/5/30 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/10/30 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/5/37.5 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/5/45 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Arm title
    		 GEN1044 Doses 1/3/60 mg
    Arm description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GEN1044
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GEN1044 was administered IV weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Number of subjects in period 1
    		GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Started
    1
    4
    7
    7
    6
    2
    4
    6
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    1
    4
    7
    7
    6
    2
    4
    6
         Adverse event, serious fatal
    -
    -
    -
    -
    1
    -
    1
    -
         Consent withdrawn by subject
    -
    -
    -
    -
    1
    -
    -
    -
         Death
    1
    2
    3
    -
    2
    -
    -
    2
         Unspecified
    -
    -
    1
    -
    -
    -
    -
    -
         Sponsor decision
    -
    2
    3
    7
    2
    2
    3
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GEN1044 Doses 0.3/3/3 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-central nervous system (non-CNS) solid tumor(s) received intravenous (IV) infusion of GEN1044 weekly (0.3 mg on Cycle [C] 1 Day (D] 1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by every 3 weeks (Q3W) until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/10 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/10/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/37.5 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/45 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/60 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg Total
    Number of subjects
    		 1 4 7 7 6 2 4 6 37
    Age categorical
    Units: Subjects
        In utero
    		 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
        Newborns (0-27 days)
    		 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
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 1 1 5 5 5 2 3 5 27
        From 65-84 years
    		 0 3 2 2 1 0 1 1 10
        85 years and over
    		 0 0 0 0 0 0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 1 2 3 3 4 1 2 3 19
        Male
    		 0 2 4 4 2 1 2 3 18

    End points

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    End points reporting groups
    Reporting group title
    GEN1044 Doses 0.3/3/3 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-central nervous system (non-CNS) solid tumor(s) received intravenous (IV) infusion of GEN1044 weekly (0.3 mg on Cycle [C] 1 Day (D] 1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by every 3 weeks (Q3W) until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/10 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/10/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/37.5 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/5/45 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 Doses 1/3/60 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Primary: Number of Participants With Dose Limiting Toxicities (DLTs)

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    End point title
    		 Number of Participants With Dose Limiting Toxicities (DLTs) [1]
    End point description
    The DLT was defined as Grade (G) >= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for >1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy’s law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity. Dose-determining set (DDS) included all participants who received at least 1 dose of study drug during the dose-escalation part, and who met the minimum exposure criterion and had sufficient safety evaluations or experienced a DLT during the first 21 days of dosing.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 21 of first cycle
    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 this end point.
    End point values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Number of subjects analysed
    1
    4
    4
    3
    2
    0 [2]
    3
    4
    Units: Participants
    0
    0
    0
    0
    1
    3
    3
    Notes
    [2] - No participant was analysed in DDS for this arm.
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [3]
    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 defined as an AE that meets one of following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an AE that jeopardizes the participant or may require medical/ surgical intervention to prevent one of the outcomes listed above [medical and scientific judgment must be exercised in deciding whether an AE is 'medically significant']); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received. The safety set was analysed which included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
    End point type
    Primary
    End point timeframe
    Day 1 through Day 263 (corresponding to maximum observed duration)
    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 this end point.
    End point values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Number of subjects analysed
    1
    4
    7
    7
    6
    2
    4
    6
    Units: Participants
        Any TEAE
    1
    4
    7
    7
    6
    2
    4
    6
        Any TESAE
    1
    1
    3
    5
    4
    1
    3
    5
    No statistical analyses for this end point

    Primary: Number of Participants With Grade >= 3 Laboratory Results

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    End point title
    		 Number of Participants With Grade >= 3 Laboratory Results [4]
    End point description
    Number of participants with laboratory measurements of Grade >= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used. The safety set was analysed which included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
    End point type
    Primary
    End point timeframe
    Day 1 through Day 263 (corresponding to maximum observed duration)
    Notes
    [4] - 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 this end point.
    End point values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Number of subjects analysed
    1
    4
    7
    7
    6
    2
    4
    6
    Units: Participants
        Lymphocyte count decreased
    1
    4
    7
    4
    5
    2
    2
    6
        Lipase increased
    0
    0
    1
    1
    0
    1
    2
    2
        Serum amylase increased
    0
    0
    1
    1
    1
    1
    1
    1
        Hypomagnesemia
    0
    0
    0
    0
    1
    0
    2
    0
        Creatinine increased
    0
    0
    0
    1
    0
    0
    1
    0
        Anemia
    0
    1
    0
    0
    0
    0
    0
    1
        Hypokalemia
    0
    1
    0
    0
    0
    0
    1
    0
        Hypoalbuminemia
    0
    0
    0
    0
    1
    0
    0
    0
        Blood bilirubin increased
    0
    0
    1
    0
    0
    0
    0
    0
        Gamma-glutamyl transferase increased
    1
    0
    0
    0
    0
    0
    0
    0
        Hypermagnesemia
    0
    0
    0
    0
    0
    0
    0
    1
        Platelet count decreased
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Complete Response (CR) or Partial Response (PR)

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    End point title
    		 Number of Participants With Complete Response (CR) or Partial Response (PR)
    End point description
    The radiological evaluation based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) was performed by investigator using computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to < 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions taking as reference the baseline sum of longest diameters. The full analysis set was analysed which included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 233 (corresponding to maximum observed duration)
    End point values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Number of subjects analysed
    1
    4
    7
    7
    6
    2
    4
    6
    Units: Participants
        Complete response
    0
    0
    0
    0
    0
    0
    0
    0
        Partial response
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044

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    End point title
    		 Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044
    End point description
    The detection and titer characterization of ADAs was performed using validated, specific, and sensitive electrochemiluminescence immunoassay (ECLIA) methods. Number of participants with ADA positive post baseline to GEN1044 are reported. Immunogenicity analysis set was analysed which included all participants who received at least 1 dose of study drug and had evaluable immunogenicity samples.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)
    End point values
    		 GEN1044 Doses 0.3/3/3 mg GEN1044 Doses 1/3/10 mg GEN1044 Doses 1/3/30 mg GEN1044 Doses 1/5/30 mg GEN1044 Doses 1/10/30 mg GEN1044 Doses 1/5/37.5 mg GEN1044 Doses 1/5/45 mg GEN1044 Doses 1/3/60 mg
    Number of subjects analysed
    1
    4
    7
    3
    6
    2
    4
    4
    Units: Participants
    0
    3
    2
    1
    0
    0
    1
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    For AEs: Day 1 through Day 263 (corresponding to maximum observed duration); For All-cause mortality: From date of inform consent form until death
    Adverse event reporting additional description
    The AEs were evaluated per the safety set. The safety set was analysed which included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    GEN1044 doses 0.3/3/3 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (0.3 mg on C1D1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/3/10 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/3/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/5/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/10/30 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/5/37.5 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/5/45 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Reporting group title
    GEN1044 doses 1/3/60 mg
    Reporting group description
    		 Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment.

    Serious adverse events
    		 GEN1044 doses 0.3/3/3 mg GEN1044 doses 1/3/10 mg GEN1044 doses 1/3/30 mg GEN1044 doses 1/5/30 mg GEN1044 doses 1/10/30 mg GEN1044 doses 1/5/37.5 mg GEN1044 doses 1/5/45 mg GEN1044 doses 1/3/60 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 1 (100.00%)
    1 / 4 (25.00%)
    3 / 7 (42.86%)
    5 / 7 (71.43%)
    4 / 6 (66.67%)
    1 / 2 (50.00%)
    3 / 4 (75.00%)
    5 / 6 (83.33%)
         number of deaths (all causes)
    1
    2
    3
    0
    4
    0
    1
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Associated Fever
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    General Physical Health Deterioration
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine Release Syndrome
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    3 / 6 (50.00%)
    0 / 2 (0.00%)
    2 / 4 (50.00%)
    3 / 6 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    10 / 10
    13 / 13
    9 / 9
    0 / 0
    9 / 9
    9 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural Effusion
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 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
    Pneumonitis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    0 / 0
    2 / 2
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Investigations
    Platelet Count Decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    Cardiac disorders
    Atrial Fibrillation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Atrial Flutter
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    Diarrhoea
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    1 / 2 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    6 / 6
    1 / 1
    6 / 6
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    Skin and subcutaneous tissue disorders
    Dermatitis Exfoliative Generalised
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 GEN1044 doses 0.3/3/3 mg GEN1044 doses 1/3/10 mg GEN1044 doses 1/3/30 mg GEN1044 doses 1/5/30 mg GEN1044 doses 1/10/30 mg GEN1044 doses 1/5/37.5 mg GEN1044 doses 1/5/45 mg GEN1044 doses 1/3/60 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 1 (100.00%)
    4 / 4 (100.00%)
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    6 / 6 (100.00%)
    2 / 2 (100.00%)
    4 / 4 (100.00%)
    5 / 6 (83.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Pain
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Flushing
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    1
    Hot Flush
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    1 / 2 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    4
    1
    2
    0
    3
    Chills
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    3 / 6 (50.00%)
    1 / 2 (50.00%)
    2 / 4 (50.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    5
    2
    3
    2
    3
    3
    Fatigue
         subjects affected / exposed
    0 / 1 (0.00%)
    4 / 4 (100.00%)
    4 / 7 (57.14%)
    0 / 7 (0.00%)
    4 / 6 (66.67%)
    1 / 2 (50.00%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    7
    8
    0
    7
    1
    3
    2
    General Physical Health Deterioration
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Non-cardiac Chest Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    2
    0
    0
    0
    0
    0
    Oedema Peripheral
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    4 / 6 (66.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    5
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    2
    1
    0
    0
    3
    Ulcer
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Cytokine Release Syndrome
         subjects affected / exposed
    1 / 1 (100.00%)
    3 / 4 (75.00%)
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    3 / 6 (50.00%)
    2 / 2 (100.00%)
    2 / 4 (50.00%)
    4 / 6 (66.67%)
         occurrences all number
    4
    10
    6
    4
    14
    4
    4
    14
    Reproductive system and breast disorders
    Vaginal Haemorrhage
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Dyspnoea
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    2 / 4 (50.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    4
    1
    0
    0
    0
    6
    5
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Pneumothorax
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Amylase Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 2 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Blood Bilirubin Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    0
    0
    Blood Creatine Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    Blood Creatinine Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    C-reactive Protein Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Electrocardiogram QT Prolonged
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    International Normalised Ratio Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Lipase Increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    2
    Lymphocyte Count Decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    Platelet Count Decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Weight Decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    Injury, poisoning and procedural complications
    Infusion Related Reaction
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    3
    3
    0
    0
    0
    0
    Overdose
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    3
    0
    0
    0
    Dysarthria
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Headache
         subjects affected / exposed
    1 / 1 (100.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 2 (50.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    1
    0
    0
    0
    2
    1
    5
    Presyncope
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Tremor
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    1
    3
    0
    0
    3
    Neutropenia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    Eye disorders
    Vision Blurred
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    2
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    1 / 1 (100.00%)
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    3 / 6 (50.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    4
    0
    3
    0
    0
    2
    Diarrhoea
         subjects affected / exposed
    1 / 1 (100.00%)
    4 / 4 (100.00%)
    6 / 7 (85.71%)
    4 / 7 (57.14%)
    5 / 6 (83.33%)
    1 / 2 (50.00%)
    4 / 4 (100.00%)
    4 / 6 (66.67%)
         occurrences all number
    1
    7
    23
    15
    13
    2
    15
    12
    Dry Mouth
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    3 / 6 (50.00%)
    1 / 2 (50.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    0
    3
    2
    0
    3
    Dyspepsia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    2
    Gastritis
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 1 (100.00%)
    3 / 4 (75.00%)
    5 / 7 (71.43%)
    4 / 7 (57.14%)
    4 / 6 (66.67%)
    1 / 2 (50.00%)
    3 / 4 (75.00%)
    5 / 6 (83.33%)
         occurrences all number
    1
    4
    9
    6
    6
    1
    6
    10
    Stomatitis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 1 (0.00%)
    3 / 4 (75.00%)
    5 / 7 (71.43%)
    2 / 7 (28.57%)
    5 / 6 (83.33%)
    0 / 2 (0.00%)
    4 / 4 (100.00%)
    4 / 6 (66.67%)
         occurrences all number
    0
    8
    10
    4
    11
    0
    8
    8
    Skin and subcutaneous tissue disorders
    Dermatitis Exfoliative Generalised
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Dry Skin
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Nail Disorder
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Palmar-plantar Erythrodysaesthesia Syndrome
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Petechiae
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Prurigo
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    Rash Maculo-papular
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    3 / 4 (75.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    4
    1
    Rash Pruritic
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    Back Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Bone Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Muscular Weakness
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Pain in Extremity
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Candida Infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Clostridium Difficile Infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Nail Infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Skin Infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    0 / 1 (0.00%)
    2 / 4 (50.00%)
    3 / 7 (42.86%)
    0 / 7 (0.00%)
    5 / 6 (83.33%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    3
    3
    0
    6
    0
    0
    3
    Dehydration
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 2 (50.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    2
    2
    Hypomagnesaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    1 / 2 (50.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    5
    2
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jan 2020
    Removed duplicate hematology and biochemistry samples collected for analysis by the central laboratory. Added clarification on which laboratory tests were to be performed by the trial center’s local laboratory and which were to be performed by a central laboratory.
    03 Apr 2020
    Incorporated Health Authority (Food and Drug Administration) feedback that recommended the following: Modified the inclusion criteria for the prostate cohort, the squamous cell carcinoma of the head and neck cohort, and the non-small cell lung cancer cohort. Relaxed the inclusion criteria to include participants with moderate renal and hepatic impairment. Excluded participants with a marked baseline prolongation of QT/corrected QT interval using Fridericia’s QT correction formula. Added pharmacokinetics (PK) collection time points. Clarified the dose administration text. Modified the dose-escalation plan for single-participant cohorts. Lowered the starting dose to 0.3 mg, which was predicted to result in a human maximum observed serum concentration more consistent with half maximal effective concentration values for cytotoxicity in pharmacology studies. Revised the DLT criteria. Revised the protocol to permanently discontinue treatment for any DLT during the dose-escalation part, and for any Grade 3 or 4 cytokine release syndrome (CRS) event during expansion. Provided dose modification guidelines for various toxicities. Provided clinical treatment guidelines for CRS management. Added hepatitis B surface antigen to the required safety laboratory tests and modified exclusion criterion to add a positive hepatitis B surface antigen result as exclusionary. Clarified various statistical sections.
    30 Mar 2021
    Updated the visit evaluation schedules tables. Adjusted PK, antidrug antibody, and electrocardiogram sampling schedules. Adjusted the biomarker schedules tables. Clarified the expansion endpoints for the exploratory objective for pharmacodynamics and potential biomarkers. Adjusted inclusion criteria to clarify the number of prior systemic treatments allowed, by cancer type, for the expansion, acceptable liver function for dose-escalation and expansion parts, and tumor biopsy requirements for dose-escalation and expansion parts. Adjusted exclusion criteria to add clarification for SARS-CoV-2 vaccination, add criterion for treatment with chimeric antigen receptor T cells, and clarify on allergic reactions. Added clarification that rescreening may only have been performed once. Updated the details on the management of CRS. Prohibited SARS-CoV-2 vaccine administration during the DLT assessment period. Added clarification on the DLT period and DLT criteria for dose-escalation as well as on the dose modification guidance and safety stopping criteria for the dose-escalation and expansion parts. Updated instructions and clarification for imaging scans, added clarifications on requirements for pregnancy testing, and updated the tests to be performed by a central laboratory. Added clarifications on biomarker assessments and the requirements for tumor biopsy. Updated AEs of special interest section to include immune effector cell associated neurotoxicity syndrome and added details for this in a new section as well as an appendix detailing management thereof.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    29 Sep 2021
    Upon review and evaluation of the overall safety profile and safety signals of GEN1044 during the Dose-escalation part, the Safety Committee decided to stop further enrollment and Genmab decided to stop the compound development.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    During dose-escalation part, Sponsor decided to stop further enrollment and the compound development. Hence, expansion part of the trial was never initiated and PK data collected during the dose-escalation part were not analyzed.
    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.

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