Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44364   clinical trials with a EudraCT protocol, of which   7388   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, multicenter, randomized, open-label, active-controlled study of DS-8201a, an anti-HER2-antibody drug conjugate, versus ado-trastuzumab emtansine (T-DM1) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane

    Summary
    EudraCT number
    		 2018-000222-61
    Trial protocol
    		 GB   BE   FR   ES   DE   IT  
    Global end of trial date

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Oct 2025
    First version publication date
    09 Jun 2022
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    This version is based on additional data generated at the second data cut off date of 25 July 2022. The study is still ongoing.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    DS8201-A-U302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03529110
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Daiichi Sankyo Inc.
    Sponsor organisation address
    211 Mt. Airy Rd., Basking Ridge, United States, 07920
    Public contact
    Global Clinical Director, Daiichi Sankyo Inc., 908 992-6400, CTRinfo_us@daiichisankyo.com
    Scientific contact
    Global Clinical Director, Daiichi Sankyo Inc., 908 992-6400, CTRinfo_us@daiichisankyo.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
    Interim
    Date of interim/final analysis
    25 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of DS 8201a to T-DM1 as measured by progression-free survival (PFS).
    Protection of trial subjects
    The study protocol, amendments, the informed consent form(s) (ICF[s]), and information sheets were approved by the appropriate and applicable Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs). The study was conducted in compliance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH) consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and applicable regulatory requirement(s).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Aug 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 99 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 14
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Brazil: 63
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    China: 65
    Country: Number of subjects enrolled
    France: 38
    Country: Number of subjects enrolled
    Hong Kong: 21
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Japan: 68
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 84
    Country: Number of subjects enrolled
    Spain: 25
    Country: Number of subjects enrolled
    Taiwan: 71
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    524
    EEA total number of subjects
    93
    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)
    418
    From 65 to 84 years
    106
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 524 participants were enrolled and treated across 14 countries. Following the primary results at the first data cutoff (21 May 2021), this report covers the second cutoff (25 July 2022) with analysis up to 47 months. Data collection is ongoing; further results will be shared at the next cutoff and upon study completion.

    Pre-assignment
    Screening details
    		 A total of 699 participants were screened and 524 participants enrolled in the Full Analysis Set; 6 participants did not receive treatment resulting in 518 participants in Safety Analysis Set

    Period 1
    Period 1 title
    DCO 25 July 2022 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Trastuzumab Deruxtecan (T-DXd)
    Arm description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).
    Arm type
    		 Experimental

    Investigational medicinal product name
    trastuzumab deruxtecan
    Investigational medicinal product code
    Other name
    T-DXd, DS-8201a, Enhertu®
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously.

    Arm title
    		 Ado-trastuzumab Emtansine (T-DM1)
    Arm description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ado-trastuzumab emtansine
    Investigational medicinal product code
    Other name
    T-DM1, KADCYLA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The treatment will be in accordance with the approved label.

    Number of subjects in period 1
    		Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Started
    261
    263
    Completed
    75
    18
    Not completed
    186
    245
         Clinical progression
    5
    14
         Physician decision
    2
    8
         Other
    6
    6
         Death
    4
    4
         Adverse event
    54
    21
         Randomized but not Treated
    4
    2
         Progressive disease
    94
    178
         Withdrawal by subject
    17
    12

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Trastuzumab Deruxtecan (T-DXd)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

    Reporting group title
    Ado-trastuzumab Emtansine (T-DM1)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.

    Reporting group values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1) Total
    Number of subjects
    		 261 263 524
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 212 206 418
        From 65-84 years
    		 41 49 90
        85 years and over
    		 8 8 16
    Age continuous
    Units: years
        median (standard deviation)
    		 54.5 ( 11.11 ) 54.2 ( 11.84 ) -
    Gender categorical
    Units: Subjects
        Female
    		 260 262 522
        Male
    		 1 1 2
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 152 162 314
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 10 9 19
        White
    		 71 72 143
        More than one race
    		 2 0 2
        Unknown or Not Reported
    		 26 20 46

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Trastuzumab Deruxtecan (T-DXd)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

    Reporting group title
    Ado-trastuzumab Emtansine (T-DM1)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.

    Primary: Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [1]
    End point description
    Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 25 Jul 2022.
    End point type
    Primary
    End point timeframe
    Up to 47 months (data cut-off)
    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: No statistical analysis was performed
    End point values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Number of subjects analysed
    261
    263
    Units: months
        median (confidence interval 95%)
    28.8 (22.4 to 37.9)
    6.8 (5.6 to 8.2)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

    		 Close Top of page
    End point title
    		 Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
    End point description
    Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 25 Jul 2022.
    End point type
    Secondary
    End point timeframe
    Up to 47 months (data cut-off)
    End point values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Number of subjects analysed
    261 [2]
    263 [3]
    Units: months
        median (confidence interval 95%)
    99.9 (40.5 to 99.9)
    99.9 (34.0 to 99.9)
    Notes
    [2] - 99.9=NA, Median and Upper CI was not estimable due to insufficient number of events.
    [3] - 99.9=NA, Median and Upper CI was not estimable due to insufficient number of events.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

    		 Close Top of page
    End point title
    		 Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
    End point description
    The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported. Objective response rate was assessed in the Full Analysis Set at data cut-off date of 25 Jul 2022.
    End point type
    Secondary
    End point timeframe
    Up to 47 months (data cut-off)
    End point values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Number of subjects analysed
    261
    263
    Units: Percentage of Participants
    number (confidence interval 95%)
        BICR
    78.5 (73.1 to 83.4)
    35.0 (29.2 to 41.1)
        Investigator Assessment
    78.9 (73.5 to 83.7)
    36.9 (31.0 to 43.0)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

    		 Close Top of page
    End point title
    		 Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
    End point description
    Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported. Duration of Response (DoR) was assessed in the Full Analysis Set of participants with confirmed CR/PR at data cut-off date of 25 Jul 2022
    End point type
    Secondary
    End point timeframe
    Up to 47 months (data cut-off)
    End point values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Number of subjects analysed
    261 [4]
    263
    Units: months
    median (confidence interval 95%)
        BICR
    36.6 (22.4 to 99.9)
    23.8 (12.6 to 34.7)
        Investigator Assessment
    30.4 (23.0 to 99.9)
    17.0 (14.1 to 24.2)
    Notes
    [4] - 99.9=NA, Upper CI was not estimable due to insufficient number of events.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
    End point description
    Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 25 Jul 2022.
    End point type
    Secondary
    End point timeframe
    Up to 47 months (data cut-off)
    End point values
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Number of subjects analysed
    261 [5]
    263
    Units: months
        median (confidence interval 95%)
    29.1 (23.7 to 99.9)
    7.2 (6.8 to 8.3)
    Notes
    [5] - 99.9=NA, Upper CI was not estimable due to insufficient number of events.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, to the data cut off date of 25 Jul 2022, up to 47 months.
    Adverse event reporting additional description
    A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25
    Reporting groups
    Reporting group title
    Trastuzumab Deruxtecan (T-DXd)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W

    Reporting group title
    Ado-trastuzumab Emtansine (T-DM1)
    Reporting group description
    		 Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.

    Serious adverse events
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    65 / 257 (25.29%)
    58 / 261 (22.22%)
         number of deaths (all causes)
    72
    97
         number of deaths resulting from adverse events
    6
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angiodysplasia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Epidural blood patch
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 257 (1.56%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    3 / 257 (1.17%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Oedema peripheral
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait inability
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 261 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    5 / 257 (1.95%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 257 (1.56%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinal cyst
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypoxia
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 257 (0.00%)
    3 / 261 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biopsy lymph gland
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation necrosis
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Altered state of consciousness
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 257 (0.78%)
    3 / 261 (1.15%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Otolithiasis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Rhegmatogenous retinal detachment
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    5 / 257 (1.95%)
    2 / 261 (0.77%)
         occurrences causally related to treatment / all
    6 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Jaundice cholestatic
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic atrophy
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Endocrine disorders
    Hypercalcaemia of malignancy
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone lesion
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    5 / 257 (1.95%)
    6 / 261 (2.30%)
         occurrences causally related to treatment / all
    3 / 6
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 257 (1.17%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 257 (0.39%)
    4 / 261 (1.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Breast cellulitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 257 (0.78%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 257 (0.00%)
    2 / 261 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Trastuzumab Deruxtecan (T-DXd) Ado-trastuzumab Emtansine (T-DM1)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    254 / 257 (98.83%)
    247 / 261 (94.64%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    16 / 257 (6.23%)
    8 / 261 (3.07%)
         occurrences all number
    25
    8
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    79 / 257 (30.74%)
    52 / 261 (19.92%)
         occurrences all number
    159
    70
    Asthenia
         subjects affected / exposed
    37 / 257 (14.40%)
    31 / 261 (11.88%)
         occurrences all number
    72
    59
    Malaise
         subjects affected / exposed
    30 / 257 (11.67%)
    9 / 261 (3.45%)
         occurrences all number
    70
    9
    Pyrexia
         subjects affected / exposed
    37 / 257 (14.40%)
    42 / 261 (16.09%)
         occurrences all number
    65
    75
    Oedema peripheral
         subjects affected / exposed
    23 / 257 (8.95%)
    10 / 261 (3.83%)
         occurrences all number
    25
    10
    Influenza like illness
         subjects affected / exposed
    18 / 257 (7.00%)
    6 / 261 (2.30%)
         occurrences all number
    26
    7
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    35 / 257 (13.62%)
    46 / 261 (17.62%)
         occurrences all number
    57
    73
    Cough
         subjects affected / exposed
    40 / 257 (15.56%)
    29 / 261 (11.11%)
         occurrences all number
    51
    34
    Dyspnoea
         subjects affected / exposed
    22 / 257 (8.56%)
    16 / 261 (6.13%)
         occurrences all number
    33
    18
    Oropharyngeal pain
         subjects affected / exposed
    14 / 257 (5.45%)
    7 / 261 (2.68%)
         occurrences all number
    17
    8
    Interstitial lung disease
         subjects affected / exposed
    13 / 257 (5.06%)
    2 / 261 (0.77%)
         occurrences all number
    14
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    21 / 257 (8.17%)
    6 / 261 (2.30%)
         occurrences all number
    23
    6
    Insomnia
         subjects affected / exposed
    20 / 257 (7.78%)
    26 / 261 (9.96%)
         occurrences all number
    24
    26
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    79 / 257 (30.74%)
    30 / 261 (11.49%)
         occurrences all number
    426
    63
    Aspartate aminotransferase increased
         subjects affected / exposed
    72 / 257 (28.02%)
    107 / 261 (41.00%)
         occurrences all number
    162
    157
    White blood cell count decreased
         subjects affected / exposed
    60 / 257 (23.35%)
    16 / 261 (6.13%)
         occurrences all number
    325
    32
    Alanine aminotransferase increased
         subjects affected / exposed
    59 / 257 (22.96%)
    82 / 261 (31.42%)
         occurrences all number
    130
    112
    Platelet count decreased
         subjects affected / exposed
    64 / 257 (24.90%)
    114 / 261 (43.68%)
         occurrences all number
    148
    198
    Blood alkaline phosphatase increased
         subjects affected / exposed
    40 / 257 (15.56%)
    34 / 261 (13.03%)
         occurrences all number
    57
    60
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    24 / 257 (9.34%)
    36 / 261 (13.79%)
         occurrences all number
    42
    61
    Blood bilirubin increased
         subjects affected / exposed
    22 / 257 (8.56%)
    13 / 261 (4.98%)
         occurrences all number
    48
    28
    Lymphocyte count decreased
         subjects affected / exposed
    15 / 257 (5.84%)
    3 / 261 (1.15%)
         occurrences all number
    35
    4
    Weight decreased
         subjects affected / exposed
    58 / 257 (22.57%)
    23 / 261 (8.81%)
         occurrences all number
    72
    26
    Weight increased
         subjects affected / exposed
    17 / 257 (6.61%)
    2 / 261 (0.77%)
         occurrences all number
    17
    2
    Blood creatinine increased
         subjects affected / exposed
    14 / 257 (5.45%)
    3 / 261 (1.15%)
         occurrences all number
    31
    7
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    12 / 257 (4.67%)
    17 / 261 (6.51%)
         occurrences all number
    16
    17
    Electrocardiogram QT prolonged
         subjects affected / exposed
    11 / 257 (4.28%)
    15 / 261 (5.75%)
         occurrences all number
    20
    25
    Nervous system disorders
    Headache
         subjects affected / exposed
    61 / 257 (23.74%)
    40 / 261 (15.33%)
         occurrences all number
    92
    54
    Dizziness
         subjects affected / exposed
    37 / 257 (14.40%)
    25 / 261 (9.58%)
         occurrences all number
    50
    28
    Peripheral sensory neuropathy
         subjects affected / exposed
    20 / 257 (7.78%)
    25 / 261 (9.58%)
         occurrences all number
    22
    28
    Dysgeusia
         subjects affected / exposed
    16 / 257 (6.23%)
    9 / 261 (3.45%)
         occurrences all number
    19
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    94 / 257 (36.58%)
    50 / 261 (19.16%)
         occurrences all number
    219
    108
    Neutropenia
         subjects affected / exposed
    44 / 257 (17.12%)
    8 / 261 (3.07%)
         occurrences all number
    119
    33
    Leukopenia
         subjects affected / exposed
    29 / 257 (11.28%)
    9 / 261 (3.45%)
         occurrences all number
    63
    23
    Lymphopenia
         subjects affected / exposed
    21 / 257 (8.17%)
    10 / 261 (3.83%)
         occurrences all number
    53
    18
    Thrombocytopenia
         subjects affected / exposed
    17 / 257 (6.61%)
    36 / 261 (13.79%)
         occurrences all number
    34
    60
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    15 / 257 (5.84%)
    5 / 261 (1.92%)
         occurrences all number
    19
    6
    Eye disorders
    Dry eye
         subjects affected / exposed
    13 / 257 (5.06%)
    10 / 261 (3.83%)
         occurrences all number
    13
    10
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    196 / 257 (76.26%)
    79 / 261 (30.27%)
         occurrences all number
    660
    107
    Vomiting
         subjects affected / exposed
    131 / 257 (50.97%)
    27 / 261 (10.34%)
         occurrences all number
    309
    34
    Constipation
         subjects affected / exposed
    95 / 257 (36.96%)
    50 / 261 (19.16%)
         occurrences all number
    167
    59
    Diarrhoea
         subjects affected / exposed
    83 / 257 (32.30%)
    20 / 261 (7.66%)
         occurrences all number
    176
    29
    Dyspepsia
         subjects affected / exposed
    31 / 257 (12.06%)
    16 / 261 (6.13%)
         occurrences all number
    34
    16
    Abdominal pain
         subjects affected / exposed
    36 / 257 (14.01%)
    6 / 261 (2.30%)
         occurrences all number
    43
    8
    Abdominal pain upper
         subjects affected / exposed
    30 / 257 (11.67%)
    14 / 261 (5.36%)
         occurrences all number
    42
    15
    Gastrooesophageal reflux disease
         subjects affected / exposed
    14 / 257 (5.45%)
    5 / 261 (1.92%)
         occurrences all number
    17
    5
    Stomatitis
         subjects affected / exposed
    46 / 257 (17.90%)
    10 / 261 (3.83%)
         occurrences all number
    63
    12
    Abdominal distension
         subjects affected / exposed
    13 / 257 (5.06%)
    6 / 261 (2.30%)
         occurrences all number
    60
    6
    Dry mouth
         subjects affected / exposed
    9 / 257 (3.50%)
    26 / 261 (9.96%)
         occurrences all number
    15
    28
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    102 / 257 (39.69%)
    9 / 261 (3.45%)
         occurrences all number
    119
    10
    Pruritus
         subjects affected / exposed
    23 / 257 (8.95%)
    19 / 261 (7.28%)
         occurrences all number
    28
    23
    Rash
         subjects affected / exposed
    18 / 257 (7.00%)
    24 / 261 (9.20%)
         occurrences all number
    23
    27
    Dry skin
         subjects affected / exposed
    15 / 257 (5.84%)
    5 / 261 (1.92%)
         occurrences all number
    16
    5
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    26 / 257 (10.12%)
    15 / 261 (5.75%)
         occurrences all number
    33
    16
    Myalgia
         subjects affected / exposed
    26 / 257 (10.12%)
    17 / 261 (6.51%)
         occurrences all number
    33
    25
    Arthralgia
         subjects affected / exposed
    41 / 257 (15.95%)
    38 / 261 (14.56%)
         occurrences all number
    50
    42
    Pain in extremity
         subjects affected / exposed
    24 / 257 (9.34%)
    21 / 261 (8.05%)
         occurrences all number
    27
    27
    Muscle spasms
         subjects affected / exposed
    12 / 257 (4.67%)
    16 / 261 (6.13%)
         occurrences all number
    18
    17
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    21 / 257 (8.17%)
    15 / 261 (5.75%)
         occurrences all number
    37
    16
    Pneumonia
         subjects affected / exposed
    15 / 257 (5.84%)
    5 / 261 (1.92%)
         occurrences all number
    16
    5
    Pneumonitis
         subjects affected / exposed
    21 / 257 (8.17%)
    3 / 261 (1.15%)
         occurrences all number
    26
    3
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 257 (8.95%)
    16 / 261 (6.13%)
         occurrences all number
    28
    18
    COVID-19
         subjects affected / exposed
    23 / 257 (8.95%)
    8 / 261 (3.07%)
         occurrences all number
    24
    8
    Nasopharyngitis
         subjects affected / exposed
    14 / 257 (5.45%)
    7 / 261 (2.68%)
         occurrences all number
    16
    9
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    77 / 257 (29.96%)
    46 / 261 (17.62%)
         occurrences all number
    202
    55
    Hypokalaemia
         subjects affected / exposed
    39 / 257 (15.18%)
    29 / 261 (11.11%)
         occurrences all number
    107
    52
    Hypoalbuminaemia
         subjects affected / exposed
    24 / 257 (9.34%)
    14 / 261 (5.36%)
         occurrences all number
    55
    35

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jun 2018
    Clarified TEAEs section. Updated dose information & modification section and inclusion & exclusion criteria section. Updated definitions of Grade 2, 3, and 4 for specific investigations. Clarified language for timing of signed and dated written consent. Clarified details of urine pregnancy test results. Clarified details of lab procedures. Added details for PK sampling.
    08 Mar 2019
    Clarified the primary objective and updated secondary endpoints. Updated inclusion and exclusion criteria. Updated and clarified AE reporting and follow-up. Updated dose modification, screening, and lab sections. Updated PK sampling times. Updated procedures section.
    26 Apr 2019
    Clarified interstitial lung disease information.
    23 Apr 2020
    Added additional analyses of PFS and OS. Updated the secondary endpoint of OS. Updated the exploratory endpoints. Updated inclusion & exclusion criteria section. Updated general statistical considerations and dose modification sections. Updated screening and lab procedures. Clarified the PK sampling and end of treatment timing. Updated AE of Special Interest. Updated the Schedule of Events section.
    25 Sep 2020
    Updated to incorporate the COVID-19 management procedures. Updated exploratory endpoints to include PFS on next line therapy. Clarified withdrawal of consent language.

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

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

    European Medicines Agency © 1995-Sat Oct 25 17:27:14 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA