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    Clinical Trial Results:
    A PHASE II ONE-ARM OPEN-LABEL NEOADJUVANT STUDY OF PEMBROLIZUMAB IN COMBINATION WITH NAB-PACLITAXEL FOLLOWED BY PEMBROLIZUMAB IN COMBINATION WITH EPIRUBICIN AND CYCLOPHOSPHAMIDE IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

    Summary
    EudraCT number
    		 2016-003102-14
    Trial protocol
    		 DE  
    Global end of trial date
    27 Aug 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Dec 2021
    First version publication date
    24 Dec 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    IFG-NIB-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03289819
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 DRKS-ID:: DRKS00011738
    Sponsors
    Sponsor organisation name
    Institut für Frauengesundheit GmbH
    Sponsor organisation address
    Universitätsstraße 21-23, Erlangen, Germany, 91054
    Public contact
    Clinical Trials Information, Institut für Frauengesundheit GmbH, +49 091318536167, nib@ifg-erlangen.de
    Scientific contact
    Clinical Trials Information, Institut für Frauengesundheit GmbH, +49 091318536167, nib@ifg-erlangen.de
    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
    05 Oct 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Aug 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Aug 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy as measured by pCR after completion of neoadjuvant chemotherapy in combination with pembrolizumab.
    Protection of trial subjects
    The clinical trial was conducted in accordance with current ethical standards, the Declaration of Helsinki from 1996 and the Guidelines of the International Conference on Harmonization Good Clinical Practice (GCP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Mar 2018
    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
    Germany: 56
    Worldwide total number of subjects
    56
    EEA total number of subjects
    56
    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)
    46
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The clinical trial was conducted in 4 main trial sites in Germany. Patients were recruited between 23.03.2018 and 08.10.2019. The date of last patient last visit was 27.08.2020. The date of database lock was on 22.01.2021.

    Pre-assignment
    Screening details
    		 A total of 56 patients signed the informed consent form and were enrolled into the NeoImmunoboost trial. Of these patients 3 patients were screening failures and excluded from the study. A total of 53 patients started trial treatment and were included in the safety analysis set. One patient withdrew consent and two patients stopped the treatment a

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

    Arms
    Arm title
    		 nab-paclitaxel/pembrolizumab followed by EC/pembrolizumab
    Arm description
    		 Patients received 12 doses of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² body surface area (BSA) in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA, q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. After the 25th patient had started trial treatment, all further included patients received 1 cycle of pembrolizumab i.v. 200 mg q3w monotherapy followed by 12 doses of weekly nab-paclitaxel i.v. 125 mg/m² BSA in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA, q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-paclitaxel
    Investigational medicinal product code
    Other name
    abraxane
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients received 125 mg/m² BSA q1w for 12 doses as i.v. infusion

    Investigational medicinal product name
    pembrolizumab
    Investigational medicinal product code
    Other name
    keytruda
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received 200 mg fixed dose as i.v. infusion q3w for 8 cycles/ q3w for 9 cycles

    Number of subjects in period 1 [1]
    		nab-paclitaxel/pembrolizumab followed by EC/pembrolizumab
    Started
    53
    Completed
    39
    Not completed
    14
         Physician decision
    1
         Consent withdrawn by subject
    1
         Adverse event, non-fatal
    4
         Tumor progression
    3
         Protocol deviation
    5
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 3 patients were entered into the trial and identified as screening failures. They have never started trial treatment.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 53 53
    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)
    		 51.5 ( 11.7 ) -
    Gender categorical
    Units: Subjects
        Female
    		 53 53
        Male
    		 0 0
    Ethnicity
    Units: Subjects
        Caucasian
    		 53 53
        Other
    		 0 0
    Menopausal state
    Units: Subjects
        Pre-/ perimenopausal
    		 30 30
        Postmenopausal
    		 23 23
    Tumor stage
    Units: Subjects
        cT1
    		 24 24
        cT2
    		 25 25
        cT3
    		 2 2
        cT4
    		 2 2
    Clinical lymph node status
    Units: Subjects
        cN0
    		 34 34
        cN1-3
    		 16 16
        cNX
    		 3 3
    Previous Lymph node Procedure
    Units: Subjects
        Yes
    		 20 20
        No
    		 33 33
    Pathological lymph node status
    Units: Subjects
        pN0
    		 6 6
        pN1-3
    		 14 14
        not applicable
    		 33 33
    cM
    Units: Subjects
        cM0
    		 51 51
        cMX
    		 1 1
        not available
    		 1 1
    Grading
    Units: Subjects
        G1
    		 0 0
        G2
    		 11 11
        G3
    		 41 41
        not available
    		 1 1
    Histological subtype
    Units: Subjects
        Ductal
    		 39 39
        Lobular
    		 1 1
        Mixed ductal/lobular
    		 2 2
        Other
    		 9 9
        not available
    		 2 2
    BRCA
    Units: Subjects
        BRCA1 mutation yes
    		 2 2
        BRCA 1 mutation no
    		 16 16
        not available
    		 35 35
    ECOG
    Units: Subjects
        ECOG 0
    		 51 51
        ECOG 1
    		 2 2
    Comorbidities
    Number of Comorbidities
    Units: Subjects
        None
    		 17 17
        One
    		 13 13
        More than 2
    		 23 23
    Initiation boost
    Units: Subjects
        yes
    		 28 28
        no
    		 25 25
    Time from primary diagnosis to therapy begin
    Units: days
        arithmetic mean (standard deviation)
    		 30.4 ( 10.3 ) -
    Time from primary diagnosis to study entry
    Units: days
        arithmetic mean (standard deviation)
    		 21.6 ( 9.9 ) -
    Subject analysis sets

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety analysis included all subjects who were randomized and had at least received one dose of IP nab-paclitaxel and/ or pembrolizumab and/ or E/C. Data collected on subjects in this subset during the period of randomization to the primary analysis data cut-off date were included, regardless of compliance with the protocol.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set included all patients who received at least who received at least one full treatment cycle q21d nab-paclitaxel (d1, d8, d15) and pembrolizumab (d1).

    Subject analysis set title
    Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol set was defined as all patients with a protocol-defined diagnosis who had at least received 2 cycles of nab-paclitaxel (reflecting 6 doses) with concomitant pembrolizumab treatment, and who had completed at least 2 cycles of epirubicin/ cyclophosphamide with concomitant pembrolizumab treatment. Subjects with deviations from the protocol-specified in- and exclusion criteria were also excluded from the per protocol set.

    Subject analysis sets values
    		 Safety analysis set Full Analysis Set Per Protocol Set
    Number of subjects
    53
    50
    39
    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)
    51.5 ( 11.7 )
    52.2 ( 11.5 )
    52.3 ( 11.5 )
    Gender categorical
    Units: Subjects
        Female
    53
    50
    39
        Male
    0
    0
    0
    Ethnicity
    Units: Subjects
        Caucasian
    53
    50
    39
        Other
    0
    0
    0
    Menopausal state
    Units: Subjects
        Pre-/ perimenopausal
    30
    27
    20
        Postmenopausal
    23
    23
    19
    Tumor stage
    Units: Subjects
        cT1
    24
    24
    20
        cT2
    25
    23
    17
        cT3
    2
    2
    1
        cT4
    2
    1
    1
    Clinical lymph node status
    Units: Subjects
        cN0
    34
    32
    24
        cN1-3
    16
    15
    13
        cNX
    3
    3
    2
    Previous Lymph node Procedure
    Units: Subjects
        Yes
    20
    19
    17
        No
    33
    31
    22
    Pathological lymph node status
    Units: Subjects
        pN0
    6
    6
    5
        pN1-3
    14
    13
    12
        not applicable
    33
    31
    22
    cM
    Units: Subjects
        cM0
    51
    49
    38
        cMX
    1
    1
    1
        not available
    1
    0
    0
    Grading
    Units: Subjects
        G1
    0
    0
    0
        G2
    11
    10
    8
        G3
    41
    39
    31
        not available
    Histological subtype
    Units: Subjects
        Ductal
    39
    36
    26
        Lobular
    1
    1
    0
        Mixed ductal/lobular
    2
    2
    2
        Other
    9
    9
    9
        not available
    2
    2
    2
    BRCA
    Units: Subjects
        BRCA1 mutation yes
    2
    2
    2
        BRCA 1 mutation no
    16
    16
    12
        not available
    35
    33
    25
    ECOG
    Units: Subjects
        ECOG 0
    51
    48
    37
        ECOG 1
    2
    2
    2
    Comorbidities
    Number of Comorbidities
    Units: Subjects
        None
    17
    16
    12
        One
    13
    11
    8
        More than 2
    23
    23
    19
    Initiation boost
    Units: Subjects
        yes
    28
    27
    23
        no
    25
    23
    16
    Time from primary diagnosis to therapy begin
    Units: days
        arithmetic mean (standard deviation)
    30.4 ( 10.3 )
    30.6 ( 10.6 )
    29.1 ( 8.9 )
    Time from primary diagnosis to study entry
    Units: days
        arithmetic mean (standard deviation)
    21.6 ( 9.9 )
    21.7 ( 10.1 )
    20.4 ( 9.1 )

    End points

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    End points reporting groups
    Reporting group title
    nab-paclitaxel/pembrolizumab followed by EC/pembrolizumab
    Reporting group description
    		 Patients received 12 doses of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² body surface area (BSA) in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA, q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. After the 25th patient had started trial treatment, all further included patients received 1 cycle of pembrolizumab i.v. 200 mg q3w monotherapy followed by 12 doses of weekly nab-paclitaxel i.v. 125 mg/m² BSA in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA, q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w.

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety analysis included all subjects who were randomized and had at least received one dose of IP nab-paclitaxel and/ or pembrolizumab and/ or E/C. Data collected on subjects in this subset during the period of randomization to the primary analysis data cut-off date were included, regardless of compliance with the protocol.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set included all patients who received at least who received at least one full treatment cycle q21d nab-paclitaxel (d1, d8, d15) and pembrolizumab (d1).

    Subject analysis set title
    Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol set was defined as all patients with a protocol-defined diagnosis who had at least received 2 cycles of nab-paclitaxel (reflecting 6 doses) with concomitant pembrolizumab treatment, and who had completed at least 2 cycles of epirubicin/ cyclophosphamide with concomitant pembrolizumab treatment. Subjects with deviations from the protocol-specified in- and exclusion criteria were also excluded from the per protocol set.

    Primary: pCR rate

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    End point title
    		 pCR rate [1]
    End point description
    ypT0/is ypN0
    End point type
    Primary
    End point timeframe
    Final surgery
    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: The null hypothesis stating that the pCR rate is at most 50% was tested with a one-sided binomial test with significance level α = 0.05
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50
    39
    Units: percent
        number (confidence interval 95%)
    66.0 (51.2 to 78.8)
    71.8 (55.1 to 85.0)
    No statistical analyses for this end point

    Secondary: Clinical response rate evaluated 6 weeks after initiation of nab-paclitaxel/ pembrolizumab

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    End point title
    		 Clinical response rate evaluated 6 weeks after initiation of nab-paclitaxel/ pembrolizumab
    End point description
    End point type
    Secondary
    End point timeframe
    6 weeks after initiation of nab-paclitaxel/ pembrolizumab
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    46
    35
    Units: percent
    number (confidence interval 95%)
        complete response
    4.3 (0.5 to 14.8)
    5.7 (0.7 to 19.2)
        partial response
    65.2 (49.8 to 78.6)
    71.4 (53.7 to 85.4)
        stable disease
    26.1 (14.3 to 41.1)
    20.0 (8.4 to 36.9)
        progressive disease
    2.2 (0.1 to 11.5)
    0 (0 to 0)
        not evaluable
    2.2 (0.1 to 11.5)
    2.9 (0.1 to 14.9)
    No statistical analyses for this end point

    Secondary: Clinical response rate evaluated before first E/C/ pembrolizumab

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    End point title
    		 Clinical response rate evaluated before first E/C/ pembrolizumab
    End point description
    End point type
    Secondary
    End point timeframe
    before first E/C/ pembrolizumab
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    45
    36
    Units: percent
    number (confidence interval 95%)
        complete response
    26.7 (14.6 to 41.9)
    30.6 (16.3 to 48.1)
        partial response
    42.2 (27.7 to 57.8)
    44.4 (27.9 to 61.9)
        stable disease
    26.7 (14.6 to 41.9)
    25 (12.1 to 42.1)
        progressive disease
    4.4 (0.5 to 15.1)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Clinical response rate evaluated 6 weeks after initiation of E/C/ pembrolizumab

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    End point title
    		 Clinical response rate evaluated 6 weeks after initiation of E/C/ pembrolizumab
    End point description
    End point type
    Secondary
    End point timeframe
    6 weeks after initiation of E/C/ pembrolizumab
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    35
    31
    Units: percent
    number (confidence interval 95%)
        complete response
    37.1 (21.5 to 55.1)
    41.9 (24.5 to 60.9)
        partial response
    31.4 (16.9 to 49.3)
    25.8 (11.9 to 44.6)
        stable disease
    28.6 (14.4 to 46.3)
    29.0 (14.2 to 48.0)
        not evaluable
    2.9 (0.1 to 14.9)
    3.2 (0.1 to 16.7)
    No statistical analyses for this end point

    Secondary: Clinical response rate evaluated at time of surgery/ end of treatment

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    End point title
    		 Clinical response rate evaluated at time of surgery/ end of treatment
    End point description
    End point type
    Secondary
    End point timeframe
    time of surgery/ end of treatment whichever is earlier
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    41
    33
    Units: percent
    number (confidence interval 95%)
        complete response
    53.7 (37.4 to 69.3)
    60.6 (42.1 to 77.1)
        partial response
    22.0 (10.6 to 37.6)
    18.2 (7.0 to 35.5)
        stable disease
    19.5 (8.8 to 34.9)
    18.2 (7.0 to 35.5)
        progressive disease
    2.4 (0.1 to 12.9)
    0 (0 to 0)
        not evaluable
    2.4 (0.1 to 12.9)
    3.0 (0.1 to 15.8)
    No statistical analyses for this end point

    Secondary: Summarized clinical response rate in the full analysis set

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    End point title
    		 Summarized clinical response rate in the full analysis set
    End point description
    End point type
    Secondary
    End point timeframe
    End of treatment
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50
    39
    Units: percent
    number (confidence interval 95%)
        complete response
    50 (35.5 to 64.5)
    59.0 (42.1 to 74.4)
        partial response
    70 (55.4 to 82.1)
    74.4 (57.9 to 87)
        stable disease
    48 (33.7 to 62.6)
    46.2 (30.1 to 62.8)
        progressive disease
    6 (1.3 to 16.5)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Global Health

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    End point title
    		 Global Health
    End point description
    Global health subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [2]
    39 [3]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    72.0 ( 15.4 )
    73.8 ( 14.3 )
        1.nbP/Pbr
    75.4 ( 17.2 )
    76.2 ( 16.9 )
        3.nbP/Pbr
    59.8 ( 20.0 )
    60.0 ( 19.5 )
        1.EC/Pbr
    52.5 ( 18.9 )
    53.7 ( 17.0 )
        3.EC/Pbr
    54.7 ( 19.0 )
    55.3 ( 19.6 )
        Surgery
    53.7 ( 20.9 )
    59.9 ( 19.5 )
        Safety-FU
    72.0 ( 15.4 )
    72.2 ( 15.5 )
    Notes
    [2] - Only questionnaires with item information were considered for analysis.
    [3] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Physical Functioning

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    End point title
    		 Physical Functioning
    End point description
    Physical Functioning subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks.
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [4]
    39 [5]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    93.1 ( 9.3 )
    92.7 ( 9.9 )
        1.nbP/Pbr
    91.2 ( 14.5 )
    90.9 ( 15.1 )
        3.nbP/Pbr
    76.2 ( 22.5 )
    76.1 ( 23.1 )
        1.EC/Pbr
    60.8 ( 25.0 )
    61.7 ( 23.1 )
        3.EC/Pbr
    61.6 ( 22.0 )
    61.2 ( 22.5 )
        Surgery
    67.2 ( 24.9 )
    67.4 ( 26.4 )
        Safety-FU
    82.0 ( 16.5 )
    81.7 ( 18.4 )
    Notes
    [4] - Only questionnaires with item information were considered for analysis.
    [5] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Role Functioning

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    End point title
    		 Role Functioning
    End point description
    Role funtioning subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [6]
    39 [7]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    84.0 ( 20.7 )
    88.1 ( 15.0 )
        1.nbP/Pbr
    84.8 ( 20.9 )
    84.8 ( 20.0 )
        3.nbP/Pbr
    60.2 ( 27.7 )
    60.3 ( 28.4 )
        1.EC/Pbr
    45.3 ( 29.4 )
    46.3 ( 29.6 )
        3.EC/Pbr
    43.2 ( 29.0 )
    43.4 ( 29.1 )
        Surgery
    48.8 ( 32.1 )
    51.6 ( 33.4 )
        Safety-FU
    68.5 ( 27.2 )
    67.9 ( 28.1 )
    Notes
    [6] - Only questionnaires with item information were considered for analysis.
    [7] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Emotional Functioning

    		 Close Top of page
    End point title
    		 Emotional Functioning
    End point description
    Emotional functioning subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [8]
    39 [9]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    62.4 ( 18.3 )
    63.6 ( 19.7 )
        1.nbP/Pbr
    65.8 ( 23.2 )
    64.4 ( 23.6 )
        3.nbP/Pbr
    69.5 ( 19.6 )
    67.9 ( 19.0 )
        1.EC/Pbr
    65.7 ( 18.0 )
    64.8 ( 18.4 )
        3.EC/Pbr
    65.1 ( 20.0 )
    65.7 ( 20.3 )
        Surgery
    64.8 ( 23.2 )
    66.4 ( 23.5 )
        Safety-FU
    75.7 ( 19.6 )
    74.4 ( 19.9 )
    Notes
    [8] - Only questionnaires with item information were considered for analysis.
    [9] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Cognitive Functioning

    		 Close Top of page
    End point title
    		 Cognitive Functioning
    End point description
    Cognitive functioning according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [10]
    39 [11]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    88.0 ( 16.3 )
    90.5 ( 14.5 )
        1.nbP/Pbr
    86.0 ( 19.3 )
    86.2 ( 20.4 )
        3.nbP/Pbr
    79.2 ( 25.2 )
    80.4 ( 26.1 )
        1.EC/Pbr
    71.7 ( 19.1 )
    72.2 ( 19.5 )
        3.EC/Pbr
    71.2 ( 26.2 )
    71.2 ( 26.4 )
        Surgery
    68.7 ( 25.9 )
    72.0 ( 23.3 )
        Safety-FU
    77.9 ( 24.5 )
    76.5 ( 25.4 )
    Notes
    [10] - Only questionnaires with item information were considered for analysis.
    [11] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Social Functioning

    		 Close Top of page
    End point title
    		 Social Functioning
    End point description
    Social functioning subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [12]
    39 [13]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    71.3 ( 26.6 )
    71.4 ( 28.0 )
        1.nbP/Pbr
    78.8 ( 23.4 )
    76.2 ( 24.7 )
        3.nbP/Pbr
    61.4 ( 25.4 )
    59.8 ( 26.0 )
        1.EC/Pbr
    51.9 ( 28.7 )
    52.8 ( 27.5 )
        3.EC/Pbr
    53.2 ( 29.6 )
    53.0 ( 28.7 )
        Surgery
    54.2 ( 32.8 )
    52.2 ( 33.0 )
        Safety-FU
    69.8 ( 23.5 )
    66.7 ( 23.6 )
    Notes
    [12] - Only questionnaires with item information were considered for analysis.
    [13] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Fatigue

    		 Close Top of page
    End point title
    		 Fatigue
    End point description
    Fatigue subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [14]
    39 [15]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    20.4 ( 14.6 )
    19.0 ( 15.0 )
        1.nbP/Pbr
    24.7 ( 20.0 )
    26.7 ( 19.7 )
        3.nbP/Pbr
    50.3 ( 25.0 )
    49.7 ( 25.3 )
        1.EC/Pbr
    59.2 ( 25.0 )
    59.0 ( 23.9 )
        3.EC/Pbr
    55.6 ( 25.9 )
    56.6 ( 27.0 )
        Surgery
    48.1 ( 30.2 )
    44.8 ( 29.5 )
        Safety-FU
    30.9 ( 23.7 )
    32.9 ( 25.1 )
    Notes
    [14] - Only questionnaires with item information were considered for analysis.
    [15] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Nausea and vomiting

    		 Close Top of page
    End point title
    		 Nausea and vomiting
    End point description
    Nausea and vomiting subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [16]
    39 [17]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    1.9 ( 4.6 )
    0.8 ( 3.6 )
        1.nbP/Pbr
    1.5 ( 6.0 )
    1.0 ( 3.9 )
        3.nbP/Pbr
    12.1 ( 19.1 )
    11.8 ( 14.5 )
        1.EC/Pbr
    10.1 ( 19.6 )
    9.3 ( 17.1 )
        3.EC/Pbr
    18.5 ( 21.4 )
    19.7 ( 22.2 )
        Surgery
    11.7 ( 22.7 )
    11.8 ( 22.8 )
        Safety-FU
    5.4 ( 13.6 )
    6.8 ( 15.5 )
    Notes
    [16] - Only questionnaires with item information were considered for analysis.
    [17] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Pain

    		 Close Top of page
    End point title
    		 Pain
    End point description
    Pain subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [18]
    39 [19]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    18.0 ( 20.9 )
    15.1 ( 18.2 )
        1.nbP/Pbr
    17.0 ( 21.7 )
    18.6 ( 23.1 )
        3.nbP/Pbr
    22.3 ( 26.4 )
    22.5 ( 24.9 )
        1.EC/Pbr
    39.5 ( 28.2 )
    38.4 ( 25.5 )
        3.EC/Pbr
    36.9 ( 24.6 )
    36.4 ( 25.8 )
        Surgery
    32.1 ( 28.8 )
    29.6 ( 26.4 )
        safety-FU
    20.7 ( 23.4 )
    20.4 ( 25.5 )
    Notes
    [18] - Only questionnaires with item information were considered for analysis.
    [19] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Dyspnea

    		 Close Top of page
    End point title
    		 Dyspnea
    End point description
    Dyspnea subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks.
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [20]
    39 [21]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    6.7 ( 16.7 )
    3.2 ( 10.0 )
        1.nbP/Pbr
    12.9 ( 21.8 )
    12.4 ( 23.0 )
        3.nbP/Pbr
    33.3 ( 29.1 )
    31.4 ( 28.4 )
        1.EC/Pbr
    38.8 ( 28.1 )
    35.2 ( 26.4 )
        3.EC/Pbr
    37.8 ( 29.6 )
    37.4 ( 28.6 )
        Surgery
    32.5 ( 28.7 )
    29.0 ( 28.2 )
        Safety-FU
    21.6 ( 30.6 )
    17.3 ( 31.2 )
    Notes
    [20] - Only questionnaires with item information were considered for analysis.
    [21] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Insomnia

    		 Close Top of page
    End point title
    		 Insomnia
    End point description
    Insomnia subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [22]
    39 [23]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    33.3 ( 28.9 )
    30.2 ( 29.6 )
        1.nbP/Pbr
    32.6 ( 29.2 )
    33.3 ( 29.1 )
        3.nbP/Pbr
    39.4 ( 32.4 )
    42.2 ( 32.1 )
        1.EC/Pbr
    50.4 ( 34.4 )
    53.7 ( 33.1 )
        3.EC/Pbr
    38.7 ( 28.9 )
    38.4 ( 30.2 )
        Surgery
    40.0 ( 32.2 )
    40.9 ( 30.7 )
        Safety-FU
    36.9 ( 34.1 )
    39.5 ( 37.0 )
    Notes
    [22] - Only questionnaires with item information were considered for analysis.
    [23] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Appetite loss

    		 Close Top of page
    End point title
    		 Appetite loss
    End point description
    Appetite loss subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [24]
    39 [25]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    6.7 ( 13.6 )
    4.8 ( 12.0 )
        1.nbP/Pbr
    7.6 ( 17.4 )
    8.6 ( 18.7 )
        3.nbP/Pbr
    22.0 ( 29.6 )
    18.6 ( 24.9 )
        1.EC/Pbr
    32.6 ( 31.3 )
    31.5 ( 30.8 )
        3.EC/Pbr
    36.0 ( 32.8 )
    37.4 ( 34.1 )
        Surgery
    34.2 ( 38.1 )
    32.3 ( 39.0 )
        Safety-FU
    11.7 ( 23.9 )
    11.1 ( 24.5 )
    Notes
    [24] - Only questionnaires with item information were considered for analysis.
    [25] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Constipation

    		 Close Top of page
    End point title
    		 Constipation
    End point description
    Constipation subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [26]
    39 [27]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    0.0 ( 0.0 )
    0.0 ( 0.0 )
        1.nbP/Pbr
    5.3 ( 16.0 )
    5.7 ( 17.1 )
        3.nbP/Pbr
    12.1 ( 22.8 )
    15.7 ( 24.9 )
        1.EC/Pbr
    14.7 ( 25.5 )
    15.7 ( 25.8 )
        3.EC/Pbr
    12.6 ( 19.8 )
    11.1 ( 17.8 )
        Surgery
    12.5 ( 26.9 )
    14.0 ( 28.3 )
        Safety-FU
    9.0 ( 18.7 )
    11.1 ( 20.7 )
    Notes
    [26] - Only questionnaires with item information were considered for analysis.
    [27] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Diarrhea

    		 Close Top of page
    End point title
    		 Diarrhea
    End point description
    Diarrhea subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [28]
    39 [29]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    12.0 ( 16.3 )
    11.1 ( 16.1 )
        1.nbP/Pbr
    7.6 ( 14.1 )
    8.6 ( 14.8 )
        3.nbP/Pbr
    18.6 ( 31.1 )
    15.7 ( 26.3 )
        1.EC/Pbr
    11.6 ( 17.6 )
    11.1 ( 17.8 )
        3.EC/Pbr
    17.1 ( 24.4 )
    15.2 ( 23.7 )
        Surgery
    15.0 ( 30.1 )
    15.1 ( 29.6 )
        Safety-FU
    7.2 ( 19.5 )
    4.9 ( 20.1 )
    Notes
    [28] - Only questionnaires with item information were considered for analysis.
    [29] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Financial difficulties

    		 Close Top of page
    End point title
    		 Financial difficulties
    End point description
    Financial difficulties subscale according to EORTC-QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [30]
    39 [31]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    10.7 ( 18.6 )
    11.1 ( 19.2 )
        1.nbP/Pbr
    15.2 ( 25.4 )
    16.2 ( 27.3 )
        3.nbP/Pbr
    21.2 ( 27.0 )
    19.6 ( 27.4 )
        1. EC/Pbr
    22.5 ( 28.8 )
    20.4 ( 27.9 )
        3. EC/Pbr
    18.0 ( 24.3 )
    16.2 ( 25.2 )
        Surgery
    18.3 ( 22.6 )
    16.1 ( 20.9 )
        Safety-FU
    18.9 ( 27.8 )
    14.8 ( 23.3 )
    Notes
    [30] - Only questionnaires with item information were considered for analysis.
    [31] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Body Image

    		 Close Top of page
    End point title
    		 Body Image
    End point description
    Body image subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [32]
    39 [33]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    91.0 ( 17.0 )
    92.9 ( 10.6 )
        1.nbP/Pbr
    85.9 ( 15.8 )
    86.5 ( 13.6 )
        3.nbP/Pbr
    70.5 ( 26.2 )
    68.1 ( 26.6 )
        1.EC/Pbr
    67.5 ( 25.3 )
    66.7 ( 25.1 )
        3.EC/Pbr
    69.4 ( 22.6 )
    69.4 ( 22.4 )
        Surgery
    69.9 ( 25.8 )
    69.9 ( 24.3 )
        Safety-FU
    82.2 ( 18.8 )
    84.6 ( 16.8 )
    Notes
    [32] - Only questionnaires with item information were considered for analysis.
    [33] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Sexual functioning

    		 Close Top of page
    End point title
    		 Sexual functioning
    End point description
    Sexual functioning subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [34]
    39 [35]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    29.2 ( 29.2 )
    26.7 ( 28.8 )
        1.nbP/Pbr
    30.2 ( 27.1 )
    26.8 ( 25.7 )
        3.nbP/Pbr
    20.2 ( 22.3 )
    13.5 ( 17.7 )
        1.EC/Pbr
    11.5 ( 18.2 )
    11.0 ( 18.1 )
        3.EC/Pbr
    12.5 ( 17.5 )
    11.5 ( 17.7 )
        Surgery
    11.1 ( 16.8 )
    6.7 ( 12.1 )
        Safety-FU
    27.0 ( 22.7 )
    26.5 ( 24.1 )
    Notes
    [34] - Only questionnaires with item information were considered for analysis.
    [35] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Sexual enjoyment

    		 Close Top of page
    End point title
    		 Sexual enjoyment
    End point description
    Sexual enjoyment subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [36]
    39 [37]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    78.8 ( 27.0 )
    79.2 ( 24.8 )
        1.nbP/Pbr
    77.8 ( 24.3 )
    73.3 ( 25.8 )
        3.nbP/Pbr
    75.0 ( 22.8 )
    74.1 ( 22.2 )
        1.EC/Pbr
    50.0 ( 23.6 )
    58.3 ( 15.4 )
        3.EC/Pbr
    51.5 ( 34.5 )
    58.3 ( 38.8 )
        Surgery
    56.7 ( 27.4 )
    46.7 ( 29.8 )
        Safety-FU
    70.2 ( 27.0 )
    74.4 ( 27.7 )
    Notes
    [36] - Only questionnaires with item information were considered for analysis.
    [37] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Future Perspective

    		 Close Top of page
    End point title
    		 Future Perspective
    End point description
    Future perspective subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [38]
    39 [39]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    36.0 ( 30.3 )
    38.1 ( 30.3 )
        1.nbP/Pbr
    41.7 ( 30.6 )
    43.8 ( 30.0 )
        3.nbP/Pbr
    41.7 ( 25.0 )
    40.2 ( 24.3 )
        1.EC/Pbr
    42.1 ( 28.6 )
    40.7 ( 28.9 )
        3.EC/Pbr
    40.5 ( 25.0 )
    40.4 ( 26.0 )
        Surgery
    45.8 ( 23.5 )
    47.3 ( 20.7 )
        Safety-FU
    55.0 ( 28.6 )
    56.8 ( 24.1 )
    Notes
    [38] - Only questionnaires with item information were considered for analysis.
    [39] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Systemic Therapy Side Effects

    		 Close Top of page
    End point title
    		 Systemic Therapy Side Effects
    End point description
    Systemic therapy side effects subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [40]
    39 [41]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    7.2 ( 6.8 )
    7.5 ( 7.2 )
        1.nbP/Pbr
    9.2 ( 9.9 )
    10.1 ( 10.0 )
        3.nbP/Pbr
    41.7 ( 15.9 )
    41.1 ( 16.8 )
        1.EC/Pbr
    43.9 ( 14.2 )
    44.0 ( 15.1 )
        3.EC/Pbr
    43.5 ( 14.0 )
    44.3 ( 14.4 )
        Surgery
    33.7 ( 18.2 )
    30.4 ( 17.6 )
        Safety-FU
    25.2 ( 16.7 )
    25.0 ( 16.8 )
    Notes
    [40] - Only questionnaires with item information were considered for analysis.
    [41] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Breast Symptoms

    		 Close Top of page
    End point title
    		 Breast Symptoms
    End point description
    Breast symptoms subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [42]
    39 [43]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    12.7 ( 14.5 )
    13.1 ( 14.6 )
        1.nbP/Pbr
    16.1 ( 18.4 )
    16.2 ( 17.1 )
        3.nbP/Pbr
    7.8 ( 10.4 )
    7.6 ( 10.1 )
        1.EC/Pbr
    11.7 ( 12.1 )
    12.3 ( 10.7 )
        3.EC/Pbr
    11.3 ( 12.6 )
    10.4 ( 12.3 )
        Surgery
    12.6 ( 15.9 )
    11.7 ( 15.1 )
        Safety-FU
    24.8 ( 21.4 )
    27.0 ( 23.2 )
    Notes
    [42] - Only questionnaires with item information were considered for analysis.
    [43] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Arm Symptoms

    		 Close Top of page
    End point title
    		 Arm Symptoms
    End point description
    Arm symptoms subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [44]
    39 [45]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    20.4 ( 15.9 )
    21.7 ( 15.1 )
        1.nbP/Pbr
    18.4 ( 18.4 )
    19.4 ( 18.5 )
        3.nbP/Pbr
    14.9 ( 19.2 )
    12.4 ( 14.9 )
        1.EC/Pbr
    16.8 ( 23.0 )
    16.7 ( 20.1 )
        3.EC/Pbr
    19.6 ( 15.6 )
    19.6 ( 16.3 )
        Surgery
    18.7 ( 20.7 )
    18.7 ( 18.4 )
        Safety-FU
    18.0 ( 18.2 )
    18.1 ( 19.3 )
    Notes
    [44] - Only questionnaires with item information were considered for analysis.
    [45] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Secondary: Upset by Hair Loss

    		 Close Top of page
    End point title
    		 Upset by Hair Loss
    End point description
    Upset by hair loss subscale according to EORTC-QLQ-BR23
    End point type
    Secondary
    End point timeframe
    Every 6 weeks
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50 [46]
    39 [47]
    Units: score on scale
    arithmetic mean (standard deviation)
        Pbr
    0.0 ( 0.0 )
    0.0 ( 0.0 )
        1.nbP/Pbr
    0.8 ( 5.0 )
    1.0 ( 5.6 )
        3.nbP/Pbr
    54.8 ( 31.1 )
    57.3 ( 28.4 )
        1.EC/Pbr
    41.0 ( 35.4 )
    40.6 ( 34.6 )
        3.EC/Pbr
    30.4 ( 32.2 )
    32.2 ( 32.1 )
        Surgery
    20.4 ( 35.0 )
    16.0 ( 31.2 )
        Safety-FU
    11.7 ( 26.3 )
    6.2 ( 22.7 )
    Notes
    [46] - Only questionnaires with item information were considered for analysis.
    [47] - Only questionnaires with item information were considered for analysis.
    No statistical analyses for this end point

    Other pre-specified: pCR rate

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    End point title
    		 pCR rate
    End point description
    ypT0 ypN0
    End point type
    Other pre-specified
    End point timeframe
    Final surgery
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50
    39
    Units: percent
        number (confidence interval 95%)
    62.0 (47.2 to 75.3)
    66.7 (49.8 to 80.9)
    No statistical analyses for this end point

    Other pre-specified: Influence of Initiation boost with pembrolizumab on pCR

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    End point title
    		 Influence of Initiation boost with pembrolizumab on pCR
    End point description
    Influence of Initiation boost with pembrolizumab on pCR (ypT0/is ypN0)
    End point type
    Other pre-specified
    End point timeframe
    Final surgery
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50
    39
    Units: percent
    number (confidence interval 95%)
        Initiation boost
    59.3 (38.8 to 77.6)
    65.2 (42.7 to 83.6)
        No initiation boost
    73.9 (51.6 to 89.8)
    81.2 (54.4 to 96.0)
    No statistical analyses for this end point

    Other pre-specified: Influence of Initiation boost with pembrolizumab on pCR

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    End point title
    		 Influence of Initiation boost with pembrolizumab on pCR
    End point description
    Influence of Initiation boost with pembrolizumab on pCR (ypT0 ypN0)
    End point type
    Other pre-specified
    End point timeframe
    Final surgery
    End point values
    		 Full Analysis Set Per Protocol Set
    Number of subjects analysed
    50
    39
    Units: percent
    number (confidence interval 95%)
        Initiation boost
    55.6 (35.3 to 74.5)
    60.9 (38.5 to 80.3)
        No initiation boost
    69.6 (47.1 to 86.8)
    75.0 (47.6 to 92.7)
    No statistical analyses for this end point

    Post-hoc: pCR rates (ypT0/is ypN0) according to CPS score

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    End point title
    		 pCR rates (ypT0/is ypN0) according to CPS score
    End point description
    End point type
    Post-hoc
    End point timeframe
    Final surgery
    End point values
    		 nab-paclitaxel/pembrolizumab followed by EC/pembrolizumab
    Number of subjects analysed
    50
    Units: percent
    number (confidence interval 95%)
        <1
    42.9 (9.9 to 81.6)
        >=1
    69.2 (52.4 to 83.0)
        >=10
    68.2 (45.1 to 86.1)
        >=20
    80.0 (44.4 to 97.5)
    No statistical analyses for this end point

    Post-hoc: pCR rates (ypT0 ypN0) according to CPS score

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    End point title
    		 pCR rates (ypT0 ypN0) according to CPS score
    End point description
    End point type
    Post-hoc
    End point timeframe
    Final surgery
    End point values
    		 nab-paclitaxel/pembrolizumab followed by EC/pembrolizumab
    Number of subjects analysed
    50
    Units: percent
    number (confidence interval 95%)
        <1
    42.9 (9.9 to 81.6)
        >=1
    66.7 (49.8 to 80.9)
        >=10
    68.2 (45.1 to 86.1)
        >=20
    80.0 (44.4 to 97.5)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Time of signing ICF until 30 days after cessation of treatment or until last study visit,whichever period is longer.
    Adverse event reporting additional description
    Adverse events are reported separately for nab-paclitaxel and pembrolizumab
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.03
    Reporting groups
    Reporting group title
    nab-Paclitaxel
    Reporting group description
    		 Patients were considered for safety analysis if they had received at least one dose of IP nab-paclitaxel.

    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Patients were considered for safety analysis if they had received at least one dose of IP pembrolizumab.

    Serious adverse events
    		 nab-Paclitaxel Pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 53 (62.26%)
    33 / 53 (62.26%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences causally related to treatment / all
    3 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    8 / 53 (15.09%)
    8 / 53 (15.09%)
         occurrences causally related to treatment / all
    1 / 9
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Autoimmune disorder
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alkaline phosphatase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Aphonia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 53 (11.32%)
    6 / 53 (11.32%)
         occurrences causally related to treatment / all
    1 / 8
    4 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Eye disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malabsorption
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomach pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash acneiform
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    0 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthyroidism
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter related infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Anorexia
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 nab-Paclitaxel Pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 53 (100.00%)
    53 / 53 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Vascular disorders
    Hot flashes
    alternative assessment type: Systematic
         subjects affected / exposed
    11 / 53 (20.75%)
    11 / 53 (20.75%)
         occurrences all number
    11
    11
    Hypertension
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Hypotension
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Lymphedema
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Phlebitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Thromboembolic event
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Chills
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    6
    6
    Edema limbs
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    4
    4
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    29 / 53 (54.72%)
    29 / 53 (54.72%)
         occurrences all number
    31
    31
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Flu like symptoms
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 53 (13.21%)
    7 / 53 (13.21%)
         occurrences all number
    8
    8
    General disorders and administration site conditions - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infusion related reaction
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Localized edema
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Reproductive system and breast disorders
    Breast pain
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    6
    6
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Cough
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    5
    5
    Dyspnea
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Epistaxis
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 53 (11.32%)
    6 / 53 (11.32%)
         occurrences all number
    6
    6
    Nasal congestion
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Productive cough
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Anxiety
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    2
    2
    Insomnia
    alternative assessment type: Systematic
         subjects affected / exposed
    11 / 53 (20.75%)
    11 / 53 (20.75%)
         occurrences all number
    11
    11
    Psychiatric disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Investigations
    Alanine aminotransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    5
    5
    Alkaline phosphatase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Aspartate aminotransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    5
    5
    Electrocardiogram QT corrected interval prolonged
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Gamma-glutamyltransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    International normalised ratio increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Investigations - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Lymphocyte count increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Neutrophil count decreased
    alternative assessment type: Systematic
         subjects affected / exposed
    27 / 53 (50.94%)
    27 / 53 (50.94%)
         occurrences all number
    35
    35
    Platelet count decreased
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Weight loss
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    White blood cell decreased
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Cardiac disorders
    Atrial fibrillation
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Left ventricular systolic dysfunction
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Palpitations
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Sinus tachycardia
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Nervous system disorders
    Concentration impairment
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Dizziness
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    8
    8
    Dysgeusia
    alternative assessment type: Systematic
         subjects affected / exposed
    12 / 53 (22.64%)
    12 / 53 (22.64%)
         occurrences all number
    12
    12
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed
    9 / 53 (16.98%)
    9 / 53 (16.98%)
         occurrences all number
    11
    11
    Hypersomnia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Nervous system disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Peripheral motor neuropathy
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 53 (11.32%)
    6 / 53 (11.32%)
         occurrences all number
    7
    7
    Peripheral sensory neuropathy
    alternative assessment type: Systematic
         subjects affected / exposed
    28 / 53 (52.83%)
    28 / 53 (52.83%)
         occurrences all number
    28
    28
    Presyncope
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Syncope
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    Anemia
    alternative assessment type: Systematic
         subjects affected / exposed
    10 / 53 (18.87%)
    10 / 53 (18.87%)
         occurrences all number
    12
    12
    Blood and lymphatic system disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    4
    4
    Febrile neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Leukocytosis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Thrombotic thrombocytopenic purpura
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Ear and labyrinth disorders
    Hearing impaired
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Tinnitus
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Vertigo
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Eye disorders
    Blurred vision
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Conjunctivitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Dry eye
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    5
    5
    Eye disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Floaters
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Retinal vascular disorder
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Watering eyes
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Gastrointestinal disorders
    Abdominal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    4
    4
    Constipation
    alternative assessment type: Systematic
         subjects affected / exposed
    8 / 53 (15.09%)
    8 / 53 (15.09%)
         occurrences all number
    9
    9
    Diarrhea
    alternative assessment type: Systematic
         subjects affected / exposed
    11 / 53 (20.75%)
    11 / 53 (20.75%)
         occurrences all number
    13
    13
    Esophageal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Gastroesophageal reflux disease
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    4
    4
    Hemorrhoids
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Mucositis oral
    alternative assessment type: Systematic
         subjects affected / exposed
    14 / 53 (26.42%)
    14 / 53 (26.42%)
         occurrences all number
    18
    18
    Nausea
    alternative assessment type: Systematic
         subjects affected / exposed
    21 / 53 (39.62%)
    21 / 53 (39.62%)
         occurrences all number
    22
    22
    Periodontal disease
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Small intestinal mucositis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Stomach pain
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    5
    5
    Hepatobiliary disorders
    Hepatobiliary disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Alopecia
    alternative assessment type: Systematic
         subjects affected / exposed
    15 / 53 (28.30%)
    15 / 53 (28.30%)
         occurrences all number
    15
    15
    Bullous dermatitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Dry skin
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    4
    4
    Erythema multiforme
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Nail discoloration
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Nail loss
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Nail ridging
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Pain of skin
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Pruritus
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Rash acneiform
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 53 (11.32%)
    6 / 53 (11.32%)
         occurrences all number
    6
    6
    Skin and subcutaneous tissue disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    19 / 53 (35.85%)
    19 / 53 (35.85%)
         occurrences all number
    20
    20
    Skin hyperpigmentation
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Skin ulceration
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Urticaria
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Renal and urinary disorders
    Renal and urinary disorders - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Endocrine disorders
    Hyperparathyroidism
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Hyperthyroidism
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    4
    4
    Hypothyroidism
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 53 (7.55%)
         occurrences all number
    4
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    5
    5
    Back pain
    alternative assessment type: Systematic
         subjects affected / exposed
    8 / 53 (15.09%)
    8 / 53 (15.09%)
         occurrences all number
    8
    8
    Bone pain
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Generalized muscle weakness
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Joint effusion
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Muscle weakness lower limb
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Musculoskeletal and connective tissue disorder - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 53 (9.43%)
    5 / 53 (9.43%)
         occurrences all number
    5
    5
    Neck pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Pain in extremity
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    4
    4
    Infections and infestations
    Breast infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Catheter related infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Infections and infestations - Other, specify
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Paronychia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Rhinitis infective
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Sinusitis
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Skin infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Tooth infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1
    Upper respiratory infection
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 53 (5.66%)
    3 / 53 (5.66%)
         occurrences all number
    3
    3
    Urinary tract infection
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    Metabolism and nutrition disorders
    Anorexia
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 53 (13.21%)
    7 / 53 (13.21%)
         occurrences all number
    7
    7
    Hypocalcaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 53 (1.89%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jun 2018
    Changes to the protocol included the addition of ECG and electrocardiography to be performed during the safety-follow-up visit. Also the collection of fecal samples was added to the exploratory trial objectives. With the publication of IB version 15 of pembrolizumab the recommendations for treating immune-related adverse events were updated. This was reflected in the trial protocol.
    10 Oct 2018
    The treatment plan was amended that all patients enrolled into the trial after the 25th patient had started trial treatment would receive one additional dose of pembrolizumab 200 mg q21d as initiation boost before receiving 12 doses of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² BSA in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA, q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. Additional biomaterial (blood, fresh tissue tumor sample, stool sample) was collected after this initiation boost. The comparison of patients receiving the initiation boost vs. patients without initiation boost was added to the exploratory study objectives.
    07 Nov 2018
    The changes regarded a prolongation of the safety follow-up period from 30 days to 120 days as recommended by the IEC. Also response evaluation was updated to reflect inflammatory carcinomas.
    11 Mar 2019
    Brexit-related changes to IMPD.
    12 Aug 2019
    Administrative changes due to Brexit.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    20 Aug 2018
    Recruitment interruption due to preparation of Amendment A03
    10 Dec 2018

    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.

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