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   43936   clinical trials with a EudraCT protocol, of which   7310   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:
    An open-label, single-arm Phase II study in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) to evaluate efficacy and safety of treatment with single agent copanlisib and the impact of biomarkers thereupon.

    Summary
    EudraCT number
    2014-004848-36
    Trial protocol
    BE   DE   GB   IT   ES   DK  
    Global end of trial date
    19 Jan 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Dec 2018
    First version publication date
    23 Dec 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BAY80-6946/17119
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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
    19 Jan 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to assess the potential efficacy (in terms of objective response) of single agent copanlisib in patients with relapsed or refractory DLBCL and assess the relationship between efficacy and a potentially predictive biomarker.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 May 2015
    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
    United Kingdom: 6
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Denmark: 4
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Singapore: 5
    Worldwide total number of subjects
    67
    EEA total number of subjects
    41
    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
    38
    85 years and over
    2

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 32 centers across 10 countries, between 08 MAY 2015 (first patient first visit) and 18 JAN 2018 (last patient last visit).

    Pre-assignment
    Screening details
    A total of 91 subjects were screened, of which 67 were assigned to study treatment and also started the treatment, and 24 were screened but never assigned to treatment. Altogether 27 subjects were excluded from the per protocol set, which comprised 40 subjects.

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

    Arms
    Arm title
    Copanlisib (BAY80-6946)
    Arm description
    Subjects assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Copanlisib
    Investigational medicinal product code
    BAY80-6946
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Starting dose 60mg for intravenous (IV) infusion as single agent on Days 1, 8, and 15 of 28-day treatment cycle; treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment.

    Number of subjects in period 1
    Copanlisib (BAY80-6946)
    Started
    67
    Included in per protocol set
    40 [1]
    Entered Safety follow-up
    56 [2]
    Entered Active follow-up
    9 [3]
    Entered Survival follow-up
    46 [4]
    Completed
    60
    Not completed
    7
         Consent withdrawn by subject
    6
         Switching to Other Therapy
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Altogether 27 patients were excluded from the per protocol set, which comprised 40 subjects.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This period excludes 2 deaths on treatment and 9 subjects entering active follow-up.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: This period incorporates safety follow-up with radiological assessments.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 21 subjects discontinued from treatment didn't enter due to withdrawal by subject(3) and death(18).

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    -

    Reporting group values
    Overall trial Total
    Number of subjects
    67 67
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    65.3 ± 14.5 -
    Gender categorical
    Units: Subjects
        Female
    28 28
        Male
    39 39
    CD79b Status
    Units: Subjects
        CD79b Mutant
    9 9
        CD79b Wild-type
    45 45
        CD79b Status Missing
    13 13
    DLBCL / Cell of Origin (COO) Subtype
    Units: Subjects
        Activated B-cell-like (ABC)
    19 19
        Germinal center B-cell-like (GCB)
    30 30
        Unclassifiable
    3 3
        DLBCL/COO Subtype Missing
    15 15
    Subject analysis sets

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Included all subjects assigned to study treatment, i.e. subject´s eligibility criteria were confirmed and the investigator intended to treat the subject

    Subject analysis set title
    Per protocol set (PPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Included all subjects with drug intake who were evaluable for the overall response assessment and without major protocol deviation effecting the primary efficacy evaluation

    Subject analysis set title
    CD79b Mutant
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b mutant classified at baseline depending on the biomarker value

    Subject analysis set title
    CD79b Wild-type
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b wild-type classified at baseline depending on biomarker value

    Subject analysis set title
    CD79b Status Missing
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b status missing at baseline

    Subject analysis set title
    Activated B-cell-like (ABC)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value

    Subject analysis set title
    Germinal center B-cell-like (GCB)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value

    Subject analysis set title
    DLBCL/COO Subtype Unclassifiable
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with unclassifiable DLBCL/COO subtype at baseline

    Subject analysis set title
    DLBCL/COO Subtype Missing
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with DLBCL/COO subtype missing at baseline

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Included all subjects with at least one study drug application

    Subject analysis sets values
    Full analysis set (FAS) Per protocol set (PPS) CD79b Mutant CD79b Wild-type CD79b Status Missing Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing Safety analysis set (SAF)
    Number of subjects
    67
    40
    9
    45
    13
    19
    30
    3
    15
    67
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    65.3 ± 14.5
    69.2 ± 12.2
    72.3 ± 8.7
    65.6 ± 13.7
    59.5 ± 18.6
    70.6 ± 11.2
    63.6 ± 14.8
    62.3 ± 13.3
    62.5 ± 17.3
    ±
    Gender categorical
    Units: Subjects
        Female
    28
    15
    1
    22
    5
    8
    13
    1
    6
        Male
    39
    25
    8
    23
    8
    11
    17
    2
    9
    CD79b Status
    Units: Subjects
        CD79b Mutant
    9
    8
        CD79b Wild-type
    45
    32
        CD79b Status Missing
    13
    0
    DLBCL / Cell of Origin (COO) Subtype
    Units: Subjects
        Activated B-cell-like (ABC)
    19
    16
        Germinal center B-cell-like (GCB)
    30
    22
        Unclassifiable
    3
    2
        DLBCL/COO Subtype Missing
    15
    0

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Copanlisib (BAY80-6946)
    Reporting group description
    Subjects assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment.

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Included all subjects assigned to study treatment, i.e. subject´s eligibility criteria were confirmed and the investigator intended to treat the subject

    Subject analysis set title
    Per protocol set (PPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Included all subjects with drug intake who were evaluable for the overall response assessment and without major protocol deviation effecting the primary efficacy evaluation

    Subject analysis set title
    CD79b Mutant
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b mutant classified at baseline depending on the biomarker value

    Subject analysis set title
    CD79b Wild-type
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b wild-type classified at baseline depending on biomarker value

    Subject analysis set title
    CD79b Status Missing
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with CD79b status missing at baseline

    Subject analysis set title
    Activated B-cell-like (ABC)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value

    Subject analysis set title
    Germinal center B-cell-like (GCB)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value

    Subject analysis set title
    DLBCL/COO Subtype Unclassifiable
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with unclassifiable DLBCL/COO subtype at baseline

    Subject analysis set title
    DLBCL/COO Subtype Missing
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Included all subjects with DLBCL/COO subtype missing at baseline

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Included all subjects with at least one study drug application

    Primary: Objective response rate (ORR) in total population based on investigator assessment

    Close Top of page
    End point title
    Objective response rate (ORR) in total population based on investigator assessment [1]
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
    End point type
    Primary
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: In this one-arm study the confidence interval can be considered to be the statistical analysis.
    End point values
    Full analysis set (FAS) Per protocol set (PPS)
    Number of subjects analysed
    67
    40
    Units: percentage of subjects
        number (confidence interval 90%)
    19.4 (11.9 to 29.1)
    25.0 (14.2 to 38.7)
    No statistical analyses for this end point

    Primary: ORR by CD79b status based on investigator assessment

    Close Top of page
    End point title
    ORR by CD79b status based on investigator assessment
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
    End point type
    Primary
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    9 [2]
    45 [3]
    13 [4]
    Units: percentage of subjects
    number (confidence interval 90%)
        Full analysis set (FAS)
    22.2 (4.1 to 55.0)
    20.0 (10.9 to 32.3)
    15.4 (2.8 to 41.0)
        Per protocol set (PPS)
    25.0 (4.6 to 60.0)
    25.0 (13.1 to 40.6)
    0 (0 to 0)
    Notes
    [2] - N=9 in full analysis set (FAS) and N=8 in per protocol set (PPS)
    [3] - N=45 in full analysis set (FAS) and N=32 in per protocol set (PPS)
    [4] - N=13 in full analysis set (FAS) and N=0 in per protocol set (PPS)
    Statistical analysis title
    ORR by CD79b Status assessed by Investigators
    Statistical analysis description
    ORR difference in FAS (N=54): ORR in CD79b mutant subgroup minus ORR in CD79b wild-type subgroup
    Comparison groups
    CD79b Mutant v CD79b Wild-type
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    2.2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -28.7
         upper limit
    32.9
    Statistical analysis title
    ORR by CD79b Status assessed by Investigators
    Statistical analysis description
    ORR difference in PPS (N=40): ORR in CD79b mutant subgroup minus ORR in CD79b wild-type subgroup
    Comparison groups
    CD79b Mutant v CD79b Wild-type
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals
    Parameter type
    ORR difference
    Point estimate
    0
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -33.5
         upper limit
    33.5

    Primary: ORR by DLBCL/COO Subtype Based on Investigator Assessment

    Close Top of page
    End point title
    ORR by DLBCL/COO Subtype Based on Investigator Assessment
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
    End point type
    Primary
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    19 [5]
    30 [6]
    3 [7]
    15 [8]
    Units: percentage of subjects
    number (confidence interval 90%)
        Full analysis set (FAS)
    31.6 (14.7 to 53.0)
    13.3 (4.7 to 28.0)
    33.3 (1.7 to 86.5)
    13.3 (2.4 to 36.3)
        Per protocol set (PPS)
    37.5 (17.8 to 60.9)
    13.6 (3.8 to 31.6)
    50.0 (2.5 to 97.5)
    0 (0 to 0)
    Notes
    [5] - N=19 in full analysis set (FAS) and N=16 in per protocol set (PPS)
    [6] - N=30 in full analysis set (FAS) and N=22 in per protocol set (PPS)
    [7] - N=3 in full analysis set (FAS) and N=2 in per protocol set (PPS)
    [8] - N=15 in full analysis set (FAS) and N=0 in per protocol set (PPS)
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in FAS (N=52): ORR in ABC subgroup minus ORR in non-ABC group (i.e. combined GCB subgroup and Unclassifiable subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    16.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -7.2
         upper limit
    39.1
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in PPS (N=40): ORR in ABC subgroup minus ORR in non-ABC group (i.e. combined GCB subgroup and Unclassifiable subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    20.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -6.8
         upper limit
    46.2
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in FAS (N=52): ORR in GCB subgroup minus ORR in non-GCB subgroup (i.e. combined ABC subgroup and Unclassifiable subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    -18.5
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -40.1
         upper limit
    4.6
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in PPS (N=40): ORR in GCB subgroup minus ORR in non-GCB subgroup (i.e. combined ABC subgroup and Unclassifiable subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    -25.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -49.1
         upper limit
    1.1
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in FAS (N=52): ORR in Unclassifiable subgroup minus ORR in ABC / GCB subgroup (i.e. combined ABC subgroup and GCB subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    12.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -42.4
         upper limit
    63.2
    Statistical analysis title
    ORR by DLBCL/COO Subtype assessed by Investigators
    Statistical analysis description
    ORR difference in PPS (N=40): ORR in Unclassifiable subgroup minus ORR in ABC / GCB subgroup (i.e. combined ABC subgroup and GCB subgroup)
    Comparison groups
    Activated B-cell-like (ABC) v Germinal center B-cell-like (GCB) v DLBCL/COO Subtype Unclassifiable
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Exact confidence intervals (CI)
    Parameter type
    ORR difference
    Point estimate
    26.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -44.3
         upper limit
    77.6

    Secondary: Duration of Response (DOR) in Total Population

    Close Top of page
    End point title
    Duration of Response (DOR) in Total Population
    End point description
    The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. subjects with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    13 [9]
    Units: days
        median (confidence interval 95%)
    132 (57 to 345)
    Notes
    [9] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    No statistical analyses for this end point

    Secondary: DOR by CD79b Status

    Close Top of page
    End point title
    DOR by CD79b Status
    End point description
    The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. subjects with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    2 [10]
    9 [11]
    2 [12]
    Units: days
        median (confidence interval 95%)
    516 (417 to 615)
    113 (39 to 272)
    113 (93 to 132)
    Notes
    [10] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    [11] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    [12] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    No statistical analyses for this end point

    Secondary: DOR by DLBCL/COO Subtype

    Close Top of page
    End point title
    DOR by DLBCL/COO Subtype
    End point description
    The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. subjects with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. "-99999" and "99999" denote that value could not be estimated due to censored data or data not available.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    6 [13]
    4 [14]
    1 [15]
    2 [16]
    Units: days
        median (confidence interval 95%)
    193 (39 to 417)
    183 (63 to 615)
    52 (-99999 to 99999)
    113 (93 to 132)
    Notes
    [13] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    [14] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    [15] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    [16] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS) in Total Population

    Close Top of page
    End point title
    Progression-free Survival (PFS) in Total Population
    End point description
    The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    67 [17]
    Units: days
        median (confidence interval 95%)
    54 (50 to 84)
    Notes
    [17] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: PFS by CD79b Status

    Close Top of page
    End point title
    PFS by CD79b Status
    End point description
    The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    9 [18]
    45 [19]
    13 [20]
    Units: days
        median (confidence interval 95%)
    73 (43 to 465)
    52 (46 to 88)
    56 (46 to 138)
    Notes
    [18] - Full analysis set (FAS)
    [19] - Full analysis set (FAS)
    [20] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: PFS by DLBCL/COO Subtype

    Close Top of page
    End point title
    PFS by DLBCL/COO Subtype
    End point description
    The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    19 [21]
    30 [22]
    3 [23]
    15 [24]
    Units: days
        median (confidence interval 95%)
    73 (44 to 101)
    52 (46 to 116)
    84 (26 to 164)
    51 (33 to 58)
    Notes
    [21] - Full analysis set (FAS)
    [22] - Full analysis set (FAS)
    [23] - Full analysis set (FAS)
    [24] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) in Total Population

    Close Top of page
    End point title
    Overall Survival (OS) in Total Population
    End point description
    The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    67 [25]
    Units: days
        median (confidence interval 95%)
    224 (104 to 327)
    Notes
    [25] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: OS by CD79b Status

    Close Top of page
    End point title
    OS by CD79b Status
    End point description
    The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause. "99999" denotes that value could not be estimated due to censored data.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    9 [26]
    45 [27]
    13 [28]
    Units: days
        median (confidence interval 95%)
    178 (57 to 99999)
    242 (73 to 385)
    224 (56 to 388)
    Notes
    [26] - Full analysis set (FAS)
    [27] - Full analysis set (FAS)
    [28] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: OS by DLBCL/COO Subtype

    Close Top of page
    End point title
    OS by DLBCL/COO Subtype
    End point description
    The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    19 [29]
    30 [30]
    3 [31]
    15 [32]
    Units: days
        median (confidence interval 95%)
    210 (63 to 421)
    287 (94 to 436)
    164 (93 to 273)
    160 (46 to 400)
    Notes
    [29] - Full analysis set (FAS)
    [30] - Full analysis set (FAS)
    [31] - Full analysis set (FAS)
    [32] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: Duration of Stable Disease (DOSD) in Total Population

    Close Top of page
    End point title
    Duration of Stable Disease (DOSD) in Total Population
    End point description
    The duration of stable disease (DOSD) was defined as the time (in days) from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier. The DOSD was only evaluated in subjects failing to achieve a best response of CR or PR, but who achieved SD (stable disease), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    14 [33]
    Units: days
        median (confidence interval 95%)
    106 (73 to 138)
    Notes
    [33] - Subjects who failed to achieve CR or PR but achieved SD in FAS assessed by the investigators
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) in Total Population

    Close Top of page
    End point title
    Disease Control Rate (DCR) in Total Population
    End point description
    The disease control rate (DCR) was defined as the percentage of subjects who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    67 [34]
    Units: percentage of subjects
        number (confidence interval 90%)
    40.3 (30.2 to 51.1)
    Notes
    [34] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: DCR by CD79b Status

    Close Top of page
    End point title
    DCR by CD79b Status
    End point description
    The disease control rate (DCR) was defined as the percentage of subjects who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    9 [35]
    45 [36]
    13 [37]
    Units: percentage of subjects
        number (confidence interval 90%)
    55.6 (25.1 to 83.1)
    40.0 (27.7 to 53.3)
    30.8 (11.3 to 57.3)
    Notes
    [35] - Full analysis set (FAS)
    [36] - Full analysis set (FAS)
    [37] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: DCR by DLBCL/COO Subtype

    Close Top of page
    End point title
    DCR by DLBCL/COO Subtype
    End point description
    The disease control rate (DCR) was defined as the percentage of subjects who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Secondary
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    19 [38]
    30 [39]
    3 [40]
    15 [41]
    Units: percentage of subjects
        number (confidence interval 90%)
    52.6 (32.0 to 72.6)
    40.0 (25.0 to 56.6)
    33.3 (1.7 to 86.5)
    26.7 (9.7 to 51.1)
    Notes
    [38] - Full analysis set (FAS)
    [39] - Full analysis set (FAS)
    [40] - Full analysis set (FAS)
    [41] - Full analysis set (FAS)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    Close Top of page
    End point title
    Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
    End point description
    A treatment-emergent AE is defined as any event arising or worsening after start of test drug administration until 30 days (modified by amendment 4) after the last test drug intake (end of Safety follow-up).
    End point type
    Secondary
    End point timeframe
    From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last subject’s first treatment or the last subject dies (whichever occurs first), with an average of 15 weeks for individual subject
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    67 [42]
    Units: subjects
        Any TEAE
    65
        Any TESAE
    44
    Notes
    [42] - Safety analysis set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to Response (TTR) in Total Population

    Close Top of page
    End point title
    Time to Response (TTR) in Total Population
    End point description
    The time to response (TTR) was defined as the time (days) from start of study treatment to the date of first observed response (first measured CR or PR). TTR was defined for responders only (i.e. patients with CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
    End point type
    Other pre-specified
    End point timeframe
    From start of study treatment assessed up to 2 years after the last subject’s first treatment or the last subject dies, whichever occurs first
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    13 [43]
    Units: days
        median (confidence interval 95%)
    52 (49 to 56)
    Notes
    [43] - Responders (i.e. subjects with a best response of CR or PR) in FAS assessed by the investigators
    No statistical analyses for this end point

    Other pre-specified: ORR in Total Population Based on Central Imaging Review

    Close Top of page
    End point title
    ORR in Total Population Based on Central Imaging Review
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
    End point type
    Other pre-specified
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    End point values
    Copanlisib (BAY80-6946)
    Number of subjects analysed
    67 [44]
    Units: percentage of subjects
        number (confidence interval 90%)
    22.4 (14.3 to 32.4)
    Notes
    [44] - Full analysis set (FAS)
    No statistical analyses for this end point

    Other pre-specified: ORR by CD79b Status Based on Central Imaging Review

    Close Top of page
    End point title
    ORR by CD79b Status Based on Central Imaging Review
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
    End point type
    Other pre-specified
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    End point values
    CD79b Mutant CD79b Wild-type CD79b Status Missing
    Number of subjects analysed
    9 [45]
    45 [46]
    13 [47]
    Units: percentage of subjects
        number (confidence interval 90%)
    44.4 (16.9 to 74.9)
    20.0 (10.9 to 32.3)
    15.4 (2.8 to 41.0)
    Notes
    [45] - Full analysis set (FAS)
    [46] - Full analysis set (FAS)
    [47] - Full analysis set (FAS)
    No statistical analyses for this end point

    Other pre-specified: ORR by DLBCL/COO Subtype Based on Central Imaging Review

    Close Top of page
    End point title
    ORR by DLBCL/COO Subtype Based on Central Imaging Review
    End point description
    The objective response rate (ORR) was defined as the percentage of subjects who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
    End point type
    Other pre-specified
    End point timeframe
    From start of study treatment assessed up to 24 weeks after the last subject fully evaluable for the primary endpoint started treatment (about 12 months)
    End point values
    Activated B-cell-like (ABC) Germinal center B-cell-like (GCB) DLBCL/COO Subtype Unclassifiable DLBCL/COO Subtype Missing
    Number of subjects analysed
    19 [48]
    30 [49]
    3 [50]
    15 [51]
    Units: percentage of subjects
        number (confidence interval 90%)
    47.4 (27.4 to 68.0)
    13.3 (4.7 to 28.0)
    0.0 (0.0 to 63.2)
    13.3 (2.4 to 36.3)
    Notes
    [48] - Full analysis set (FAS)
    [49] - Full analysis set (FAS)
    [50] - Full analysis set (FAS)
    [51] - Full analysis set (FAS)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last subject’s first treatment or the last subject dies (whichever occurs first), with an average of 15 weeks for individual subject
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Copanlisib (BAY80-6946)
    Reporting group description
    Subjects assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment

    Serious adverse events
    Copanlisib (BAY80-6946)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    44 / 67 (65.67%)
         number of deaths (all causes)
    53
         number of deaths resulting from adverse events
    14
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Inflammatory carcinoma of the breast
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mycosis fungoides
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Fatigue
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pyrexia
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    9 / 67 (13.43%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 8
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cough
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Neurological symptom
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nausea
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombophlebitis septic
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infection
         subjects affected / exposed
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Splenic infection fungal
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic infection fungal
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Dehydration
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    5 / 67 (7.46%)
         occurrences causally related to treatment / all
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    Copanlisib (BAY80-6946)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    64 / 67 (95.52%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    4
    Vascular disorders
    Haematoma
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Hypertension
         subjects affected / exposed
    27 / 67 (40.30%)
         occurrences all number
    42
    Hypotension
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Chest pain
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Chills
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Fatigue
         subjects affected / exposed
    18 / 67 (26.87%)
         occurrences all number
    19
    Mucosal inflammation
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    4
    Oedema peripheral
         subjects affected / exposed
    7 / 67 (10.45%)
         occurrences all number
    7
    Pyrexia
         subjects affected / exposed
    12 / 67 (17.91%)
         occurrences all number
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 67 (17.91%)
         occurrences all number
    12
    Dyspnoea
         subjects affected / exposed
    5 / 67 (7.46%)
         occurrences all number
    5
    Productive cough
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    4
    Oropharyngeal pain
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Investigations
    Lipase increased
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    4
    Platelet count decreased
         subjects affected / exposed
    5 / 67 (7.46%)
         occurrences all number
    5
    Weight decreased
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    White blood cell count decreased
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    4
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    6
    Headache
         subjects affected / exposed
    9 / 67 (13.43%)
         occurrences all number
    9
    Paraesthesia
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 67 (8.96%)
         occurrences all number
    6
    Neutropenia
         subjects affected / exposed
    9 / 67 (13.43%)
         occurrences all number
    9
    Thrombocytopenia
         subjects affected / exposed
    6 / 67 (8.96%)
         occurrences all number
    6
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    5 / 67 (7.46%)
         occurrences all number
    5
    Constipation
         subjects affected / exposed
    11 / 67 (16.42%)
         occurrences all number
    11
    Diarrhoea
         subjects affected / exposed
    25 / 67 (37.31%)
         occurrences all number
    38
    Mouth ulceration
         subjects affected / exposed
    8 / 67 (11.94%)
         occurrences all number
    8
    Nausea
         subjects affected / exposed
    20 / 67 (29.85%)
         occurrences all number
    23
    Stomatitis
         subjects affected / exposed
    5 / 67 (7.46%)
         occurrences all number
    5
    Vomiting
         subjects affected / exposed
    12 / 67 (17.91%)
         occurrences all number
    13
    Paraesthesia oral
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    5
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    6 / 67 (8.96%)
         occurrences all number
    7
    Rash
         subjects affected / exposed
    9 / 67 (13.43%)
         occurrences all number
    10
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    4
    Muscle spasms
         subjects affected / exposed
    6 / 67 (8.96%)
         occurrences all number
    7
    Pain in extremity
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    5
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    21 / 67 (31.34%)
         occurrences all number
    27
    Hypoglycaemia
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    3
    Hypokalaemia
         subjects affected / exposed
    8 / 67 (11.94%)
         occurrences all number
    15
    Hyponatraemia
         subjects affected / exposed
    4 / 67 (5.97%)
         occurrences all number
    6
    Hypophosphataemia
         subjects affected / exposed
    3 / 67 (4.48%)
         occurrences all number
    4
    Decreased appetite
         subjects affected / exposed
    10 / 67 (14.93%)
         occurrences all number
    14

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jan 2016
    •Removal of a response requirement to first-line therapy for NHL transformed from follicular lymphoma •Removal of the exclusion of patients with fasting plasma glucose > 160 mg/dL at screening •Removal of the conservative requirement for blood pressure levels during eligibility evaluation •Updates to the management and monitoring of transient glucose increases •Modification of guidelines on dose modification of study treatment for non-hematological toxicity •Guidance on the differentiation of non-infectious pneumonitis (NIP) and other pneumonitis included, and alterations to the dose-modification of study treatment in the event of NIP •Revision of laboratory evaluations and clarification that laboratory tests considered clinically significant should have been reported as an AE •Update copanlisib safety information pertaining to potential drug-related transient blood pressure increase •Fasting for lipid panels was revised to reflect local standards rather than a centrally defined period.
    21 Jul 2016
    •Implementation of ongoing central review rather than retrospective central image review •Clarification that primary analysis of efficacy was based upon the investigator’s assessment. •Clarification that AEs were collected until 30 days after last treatment with study drug. •Addition of guidance on the monitoring and prophylaxis of opportunistic infections in patients at risk for such whilst on study treatment, including additional CD4, CD8, cytomegalovirus (CMV) and blood culture laboratory tests and lung examinations, following Health Authority alerts, and allowance of a delay in study drug administration of up to 2 cycles due to reactivation of CMV.

    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA