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    Clinical Trial Results:
    A Randomized, Double-blind, Phase 3 Study Evaluating the Efficacy and Safety of ABP 980 Compared With Trastuzumab in Subjects With HER2 Positive Early Breast Cancer

    Summary
    EudraCT number
    		 2012-004319-29
    Trial protocol
    		 GB   DE   HU   SK   IT   CZ   ES   GR   BG   PL   RO  
    Global end of trial date
    27 Jan 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Feb 2018
    First version publication date
    01 Feb 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20120283
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01901146
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 01320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Jan 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the treatment effect of ABP 980 with trastuzumab on pathologic complete response (pCR) in women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.
    Protection of trial subjects
    This study was conducted in compliance with independent ethics committees (IECs), institutional review boards (IRBs), and the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, in accordance with applicable regulations regarding clinical safety data management (E2A, E2B [R3]), European Community directives 2001/20, 2001/83, 2003/94 and 2005/28 as enacted into local law, and with ICH guidelines regarding scientific integrity (E4, E8, E9 and E10). The investigator explained the benefits and risks of participation in the study to each subject or the subject’s legally acceptable representative or impartial witness and obtained written informed consent. Written informed consent was required to be obtained before the subject entering the study and before initiation of any study-related procedure.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Apr 2013
    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
    Russian Federation: 238
    Country: Number of subjects enrolled
    Ukraine: 66
    Country: Number of subjects enrolled
    Poland: 57
    Country: Number of subjects enrolled
    Belarus: 52
    Country: Number of subjects enrolled
    Romania: 44
    Country: Number of subjects enrolled
    Hungary: 28
    Country: Number of subjects enrolled
    Serbia: 27
    Country: Number of subjects enrolled
    Slovakia: 14
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    Czech Republic: 8
    Country: Number of subjects enrolled
    Mexico: 37
    Country: Number of subjects enrolled
    South Africa: 28
    Country: Number of subjects enrolled
    Brazil: 21
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Chile: 3
    Country: Number of subjects enrolled
    Spain: 44
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Germany: 18
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    United Kingdom: 3
    Worldwide total number of subjects
    725
    EEA total number of subjects
    250
    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)
    622
    From 65 to 84 years
    102
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 123 sites in 20 countries from April 2013 to January 2017. The study consisted of a neoadjuvant treatment phase for 4 cycles, surgery, and adjuvant treatment for up to one year from the first day of investigational product (IP) administration in the neoadjuvant phase.

    Pre-assignment
    Screening details
    		 Enrolled patients received run-in chemotherapy consisting of epirubicin and cyclophosphamide every 3 weeks for 4 cycles. After the run-in, participants with adequate cardiac function were randomized. Randomization was stratified by tumor stage, nodal status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.

    Period 1
    Period 1 title
    Neoadjuvant Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ABP 980
    Arm description
    		 Participants received ABP 980 at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABP 980
    Investigational medicinal product code
    ABP 980
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ABP 980 was administered at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

    Arm title
    		 Trastuzumab
    Arm description
    		 Participants received trastuzumab at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Herceptin®
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Trastuzumab was administered at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

    Number of subjects in period 1
    		ABP 980 Trastuzumab
    Started
    364
    361
    Completed
    358
    347
    Not completed
    6
    14
         Physician decision
    1
    2
         Consent withdrawn by subject
    2
    5
         Death
    1
    2
         Disease progression or recurrence
    2
    3
         Lost to follow-up
    -
    1
         Requirement for alternative therapy
    -
    1
    Period 2
    Period 2 title
    Adjuvant Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ABP 980/ABP 980
    Arm description
    		 After surgery, participants initially randomized to ABP 980 continued to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABP 980
    Investigational medicinal product code
    ABP 980
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ABP 980 was administered at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day investigational product was administered in the neoadjuvant phase. At the start of the adjuvant phase, if the first dose of ABP 980 was > 4 weeks from the last dose of investigational product administered in the neoadjuvant phase, then the first dose was to be administered as a re-loading dose of 8 mg/kg.

    Arm title
    		 Trastuzumab/Trastuzumab
    Arm description
    		 After surgery, participants originally randomized to trastuzumab were re-randomized and continued to receive trastuzumab at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Herceptin®
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Trastuzumab was administered at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day investigational product was administered in the neoadjuvant phase. At the start of the adjuvant phase if the first dose of trastuzumab was > 4 weeks from the last dose of trastuzumab administered in the neoadjuvant phase, then the first dose of investigational product was administered as a re-loading dose at 8 mg/kg.

    Arm title
    		 Trastuzumab/ABP 980
    Arm description
    		 After surgery, participants originally randomized to trastuzumab were re-randomized and switched to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABP 980
    Investigational medicinal product code
    ABP 980
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ABP 980 was administered at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day investigational product was administered in the neoadjuvant phase. At the start of the adjuvant phase, if the first dose of ABP 980 was > 4 weeks from the last dose of investigational product administered in the neoadjuvant phase, then the first dose was to be administered as a re-loading dose of 8 mg/kg.

    Number of subjects in period 2 [1]
    		ABP 980/ABP 980 Trastuzumab/Trastuzumab Trastuzumab/ABP 980
    Started
    349
    171
    171
    Completed
    323
    164
    157
    Not completed
    26
    7
    14
         Physician decision
    9
    2
    4
         Consent withdrawn by subject
    4
    1
    4
         Other
    1
    -
    -
         Death
    -
    -
    3
         Disease progression or recurrence
    12
    4
    3
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Fourteen subjects discontinued the study after surgery but before entering the adjuvant phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ABP 980
    Reporting group description
    		 Participants received ABP 980 at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.

    Reporting group title
    Trastuzumab
    Reporting group description
    		 Participants received trastuzumab at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.

    Reporting group values
    		 ABP 980 Trastuzumab Total
    Number of subjects
    		 364 361 725
    Age Categorical
    Units: Subjects
        < 50 years
    		 140 134 274
        ≥ 50 years
    		 224 227 451
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 52.8 ± 10.72 52.7 ± 11.29 -
    Gender Categorical
    Units: Subjects
        Female
    		 364 361 725
        Male
    		 0 0 0
    Race
    Units: Subjects
        White
    		 331 333 664
        Black or African American
    		 10 4 14
        Asian
    		 2 3 5
        American Indian or Alaska Native
    		 1 0 1
        Native Hawaiian or other Pacific Islander
    		 0 0 0
        Other
    		 20 21 41
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 32 36 68
        Not Hispanic or Latino
    		 332 324 656
        Not allowed to collect
    		 0 1 1
    Tumor Stage
    Units: Subjects
        < T 4
    		 282 281 563
        T4
    		 82 80 162
    Axilla Lymph Node Involvement
    Units: Subjects
        Yes
    		 277 266 543
        No
    		 87 95 182
    Hormone Receptor Status
    Units: Subjects
        Estrogen and/or progesterone receptor positive
    		 265 268 533
        Estrogen and progesterone receptor negative
    		 99 93 192
    Paclitaxel Dosing Schedule
    Units: Subjects
        Every 3 weeks
    		 256 258 514
        Every week
    		 108 103 211
    Geographic Region
    Units: Subjects
        Eastern Europe
    		 271 273 544
        Western Europe
    		 43 46 89
        Other
    		 50 42 92

    End points

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    End points reporting groups
    Reporting group title
    ABP 980
    Reporting group description
    		 Participants received ABP 980 at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.

    Reporting group title
    Trastuzumab
    Reporting group description
    		 Participants received trastuzumab at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.
    Reporting group title
    ABP 980/ABP 980
    Reporting group description
    		 After surgery, participants initially randomized to ABP 980 continued to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Reporting group title
    Trastuzumab/Trastuzumab
    Reporting group description
    		 After surgery, participants originally randomized to trastuzumab were re-randomized and continued to receive trastuzumab at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Reporting group title
    Trastuzumab/ABP 980
    Reporting group description
    		 After surgery, participants originally randomized to trastuzumab were re-randomized and switched to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Primary: Percentage of Participants with a Pathologic Complete Response

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    End point title
    		 Percentage of Participants with a Pathologic Complete Response
    End point description
    Pathologic complete response (pCR) was defined as the absence of invasive tumor cells in the breast tissue and in axillary lymph nodes, regardless of residual ductal carcinoma in situ (DCIS). The primary efficacy analysis was based on local pathology evaluation of the tumor samples using the pCR evaluable population, which included all randomized subjects who received any amount of investigational product, underwent the surgery, and had a non-missing evaluable pCR assessment from the local laboratory evaluation.
    End point type
    Primary
    End point timeframe
    3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase
    End point values
    		 ABP 980 Trastuzumab
    Number of subjects analysed
    358 [1]
    338 [2]
    Units: percentage of participants
        number (not applicable)
    48.0
    40.5
    Notes
    [1] - pCR Evaluable Population
    [2] - pCR Evaluable Population
    Statistical analysis title
    		 Risk Difference Analysis
    Statistical analysis description
    The clinical equivalence between ABP 980 and trastuzumab was first evaluated by comparing the 2-sided 90% CI of the risk difference (RD) of pCR between ABP 980 and trastuzumab estimated using a generalized linear model adjusted for stratification factors, with the margin of (-13%, 13%).
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0508 [3]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk difference (RD)
    Point estimate
    7.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 13.4
    Notes
    [3] - Generalized linear model adjusted for the randomization stratification factors tumor(T)-stage, nodal status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.
    Statistical analysis title
    		 Risk Ratio Analysis
    Statistical analysis description
    If the test of equivalence on the RD of pCR was successful, then equivalence was tested on the risk ratio (RR) of pCR at a 2-sided significance level of 0.05 by comparing the 2-sided 90% CI of the RR of pCR between ABP 980 and trastuzumab estimated using a generalized linear model adjusted for stratification factors, with the margin of (0.7586, 1/0.7586). If the test of equivalence on the RD was not successful, the RR of pCR and 90% CI were considered to be descriptive.
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.043 [4]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.1877
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.0327
         upper limit
    		 1.366
    Notes
    [4] - Generalized linear model adjusted for the randomization stratification factors T-stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.

    Secondary: Percentage of Participants with a Pathologic Complete Response in Breast Tissue Only

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    End point title
    		 Percentage of Participants with a Pathologic Complete Response in Breast Tissue Only
    End point description
    Pathologic complete response (pCR) was defined as the absence of invasive tumor cells in the breast tissue, regardless of residual ductal carcinoma in situ (DCIS). The primary efficacy analysis was based on local pathology evaluation of the tumor samples using the pCR evaluable population, which included all randomized subjects who received any amount of investigational product, underwent the surgery, and had a non-missing evaluable pCR assessment from the local laboratory evaluation.
    End point type
    Secondary
    End point timeframe
    3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase
    End point values
    		 ABP 980 Trastuzumab
    Number of subjects analysed
    358 [5]
    338 [6]
    Units: percentage of participants
        number (not applicable)
    51.1
    45.0
    Notes
    [5] - pCR Evaluable Population
    [6] - pCR Evaluable Population
    Statistical analysis title
    		 Risk Ratio Analysis
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0807 [7]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.1463
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.008
         upper limit
    		 1.3035
    Notes
    [7] - Generalized linear model adjusted for the randomization stratification factors T-stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.
    Statistical analysis title
    		 Risk Difference Analysis
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.1086 [8]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 12.2
    Notes
    [8] - Generalized linear model adjusted for the randomization stratification factors T-stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.

    Secondary: Percentage of Participants with a Pathologic Complete Response in Breast Tissue and Axillary Lymph Nodes and Absence of DCIS

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    End point title
    		 Percentage of Participants with a Pathologic Complete Response in Breast Tissue and Axillary Lymph Nodes and Absence of DCIS
    End point description
    Pathological complete response was defined as the absence of invasive tumor cells in the breast tissue and axillary lymph node(s) and absence of residual DCIS. The analysis was based on local pathology evaluation of the tumor samples using the pCR evaluable population, which included all randomized subjects who received any amount of investigational product, underwent the surgery, and had a non-missing evaluable pCR assessment from the local laboratory evaluation.
    End point type
    Secondary
    End point timeframe
    3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase
    End point values
    		 ABP 980 Trastuzumab
    Number of subjects analysed
    358 [9]
    338 [10]
    Units: percentage of participants
        number (not applicable)
    37.7
    29.6
    Notes
    [9] - pCR Evaluable Population
    [10] - pCR Evaluable Population
    Statistical analysis title
    		 Risk Difference Analysis
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0253 [11]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk difference (RD)
    Point estimate
    8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 13.9
    Notes
    [11] - Generalized linear model adjusted for the randomization stratification factors T-stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.
    Statistical analysis title
    		 Risk Ratio Analysis
    Comparison groups
    ABP 980 v Trastuzumab
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0245 [12]
    Method
    		 Generalized linear model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.2746
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.0673
         upper limit
    		 1.5222
    Notes
    [12] - Generalized linear model adjusted for the randomization stratification factors T-stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographic region.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Neoadjuvant phase: From the first dose of IP to 30 days after last dose in the neoadjuvant phase or the start of adjuvant phase; up to 16 weeks. Adjuvant phase: From the first dose of IP after surgery until 30 days after last dose; approximately 40 weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Neoadjuvant Phase: Trastuzumab
    Reporting group description
    		 Participants received trastuzumab at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.

    Reporting group title
    Neoadjuvant Phase: ABP 980
    Reporting group description
    		 Participants received ABP 980 at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus paclitaxel at 175 mg/m² Q3W for 4 cycles.

    Reporting group title
    Adjuvant Phase: Trastuzumab/Trastuzumab
    Reporting group description
    		 After surgery, participants originally randomized to trastuzumab continued to receive trastuzumab at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Reporting group title
    Adjuvant Phase: Trastuzumab/ABP 980
    Reporting group description
    		 After surgery, participants originally randomized to trastuzumab were switched to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Reporting group title
    Adjuvant Phase: ABP 980/ABP 980
    Reporting group description
    		 After surgery, participants initially randomized to ABP 980 continued to receive ABP 980 at a dose of 6 mg/kg IV infusion Q3W for up to 1 year from the first day of investigational product administration in the neoadjuvant phase.

    Serious adverse events
    		 Neoadjuvant Phase: Trastuzumab Neoadjuvant Phase: ABP 980 Adjuvant Phase: Trastuzumab/Trastuzumab Adjuvant Phase: Trastuzumab/ABP 980 Adjuvant Phase: ABP 980/ABP 980
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 361 (1.39%)
    18 / 364 (4.95%)
    6 / 171 (3.51%)
    6 / 171 (3.51%)
    18 / 349 (5.16%)
         number of deaths (all causes)
    0
    1
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to adrenals
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hysterectomy
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast haematoma
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Drug dispensing error
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound decomposition
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 361 (0.00%)
    3 / 364 (0.82%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enterocolitis
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute prerenal failure
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision site infection
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 361 (0.00%)
    2 / 364 (0.55%)
    2 / 171 (1.17%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    1 / 171 (0.58%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    1 / 349 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound sepsis
         subjects affected / exposed
    1 / 361 (0.28%)
    0 / 364 (0.00%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 361 (0.00%)
    1 / 364 (0.27%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    0 / 349 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Neoadjuvant Phase: Trastuzumab Neoadjuvant Phase: ABP 980 Adjuvant Phase: Trastuzumab/Trastuzumab Adjuvant Phase: Trastuzumab/ABP 980 Adjuvant Phase: ABP 980/ABP 980
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    220 / 361 (60.94%)
    227 / 364 (62.36%)
    49 / 171 (28.65%)
    60 / 171 (35.09%)
    124 / 349 (35.53%)
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    0 / 361 (0.00%)
    0 / 364 (0.00%)
    17 / 171 (9.94%)
    16 / 171 (9.36%)
    37 / 349 (10.60%)
         occurrences all number
    0
    0
    21
    16
    41
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    43 / 361 (11.91%)
    51 / 364 (14.01%)
    3 / 171 (1.75%)
    2 / 171 (1.17%)
    8 / 349 (2.29%)
         occurrences all number
    64
    65
    3
    2
    9
    Paraesthesia
         subjects affected / exposed
    21 / 361 (5.82%)
    17 / 364 (4.67%)
    0 / 171 (0.00%)
    1 / 171 (0.58%)
    6 / 349 (1.72%)
         occurrences all number
    34
    26
    0
    1
    7
    Peripheral sensory neuropathy
         subjects affected / exposed
    22 / 361 (6.09%)
    25 / 364 (6.87%)
    0 / 171 (0.00%)
    0 / 171 (0.00%)
    3 / 349 (0.86%)
         occurrences all number
    29
    31
    0
    0
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    38 / 361 (10.53%)
    40 / 364 (10.99%)
    7 / 171 (4.09%)
    10 / 171 (5.85%)
    17 / 349 (4.87%)
         occurrences all number
    61
    54
    10
    19
    24
    Leukopenia
         subjects affected / exposed
    16 / 361 (4.43%)
    21 / 364 (5.77%)
    5 / 171 (2.92%)
    8 / 171 (4.68%)
    15 / 349 (4.30%)
         occurrences all number
    20
    26
    10
    17
    24
    Neutropenia
         subjects affected / exposed
    45 / 361 (12.47%)
    53 / 364 (14.56%)
    10 / 171 (5.85%)
    6 / 171 (3.51%)
    25 / 349 (7.16%)
         occurrences all number
    75
    81
    15
    8
    52
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    59 / 361 (16.34%)
    54 / 364 (14.84%)
    7 / 171 (4.09%)
    10 / 171 (5.85%)
    17 / 349 (4.87%)
         occurrences all number
    120
    113
    8
    10
    23
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    19 / 361 (5.26%)
    23 / 364 (6.32%)
    2 / 171 (1.17%)
    4 / 171 (2.34%)
    9 / 349 (2.58%)
         occurrences all number
    21
    35
    3
    5
    9
    Nausea
         subjects affected / exposed
    18 / 361 (4.99%)
    21 / 364 (5.77%)
    3 / 171 (1.75%)
    2 / 171 (1.17%)
    11 / 349 (3.15%)
         occurrences all number
    39
    28
    4
    2
    18
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    23 / 361 (6.37%)
    19 / 364 (5.22%)
    0 / 171 (0.00%)
    2 / 171 (1.17%)
    3 / 349 (0.86%)
         occurrences all number
    24
    19
    0
    2
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    55 / 361 (15.24%)
    63 / 364 (17.31%)
    9 / 171 (5.26%)
    9 / 171 (5.26%)
    20 / 349 (5.73%)
         occurrences all number
    138
    145
    9
    11
    24
    Bone pain
         subjects affected / exposed
    29 / 361 (8.03%)
    12 / 364 (3.30%)
    0 / 171 (0.00%)
    3 / 171 (1.75%)
    1 / 349 (0.29%)
         occurrences all number
    62
    24
    0
    5
    1
    Myalgia
         subjects affected / exposed
    31 / 361 (8.59%)
    34 / 364 (9.34%)
    3 / 171 (1.75%)
    2 / 171 (1.17%)
    2 / 349 (0.57%)
         occurrences all number
    50
    54
    3
    2
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2012
    The primary purpose of the change in version 1.1 (08 October 2012) was administrative.
    21 May 2013
    The primary purposes of changes in version 2.0 were the following: - to update the power calculations to reflect updated assumptions, including increasing the number of subjects and sites and the duration of the study - to add RD of pCR in breast tissue and axillary lymph nodes as a co-primary endpoint and make appropriate updates to the statistical methods, including sequential testing - to add RD of pCR in breast tissue and RD of pCR in breast tissue and axillary lymph nodes and absence of DCIS as secondary endpoints - to define a pCR evaluable population - to modify the restrictions on chemotherapy pretreatment regimens and treatment regimens for chemotherapy-associated toxicities to accommodate differing international standards - to specify that adequate cardiac function is required after run-in chemotherapy for starting treatment with investigational product; at all indicated visits, echocardiogram was required and results were required to be obtained before treatment with investigational product - to delete the option for a third dose decrease in the case of grade 2 hepatic toxicities - to specify that the formal interim analysis would be performed when 1/3 of subjects had been assessed for pCR
    06 Aug 2015
    The primary purposes of the changes in version 3.0 were the following: - to revise the period of required contraception use for women of childbearing potential, to 7 months after the last dose of study drug - to allow dose to be recalculated for subjects who underwent a > 10% change in weight from baseline - to update the statistical sections, including definitions of the analysis populations, to incorporate feedback received from agencies at that time - to allow flexibility in use the of granulocyte-colony stimulating factor (GCSF) to reflect different international standards

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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