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   44389   clinical trials with a EudraCT protocol, of which   7402   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:
    AtTEnd: Atezolizumab Trial in Endometrial cancer - Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with paclitaxel and carboplatin in women with advanced/recurrent endometrial cancer.

    Summary
    EudraCT number
    		 2018-001072-37
    Trial protocol
    		 GB   AT   ES   DE   IT  
    Global end of trial date
    20 Jan 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Feb 2026
    First version publication date
    18 Feb 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IRFMN-EN-7556
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03603184
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    IRCCS Istituto di Ricerche Farmacologiche Mario Negri IRCCS
    Sponsor organisation address
    Via Mario Negri 2, Milan, Italy, 20156
    Public contact
    Laboratorio Metodologia per la rice, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, 0039 0239014648, attend@marionegri.it
    Scientific contact
    Laboratorio Metodologia per la rice, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, 0039 0239014648, attend@marionegri.it
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Aug 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Jan 2025
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jan 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy in terms of PFS and OS of first-line atezolizumab versus placebo in combination with carboplatin and paclitaxel in patients with advanced stage III/IV or recurrent endometrial cancer.
    Protection of trial subjects
    The protection of trial subjects was ensured by a favorable risk/benefit assessment and by conducting the study in accordance with the Declaration of Helsinki, ICH Good Clinical Practice (GCP) guidelines, and applicable regulatory requirements. Written informed consent was obtained from all participants prior to any study-related procedures. Subject confidentiality was maintained in compliance with GDPR through data anonymization and/or pseudonymization. Subject safety was closely monitored throughout the study, including appropriate management and reporting of adverse events. Participants were free to withdraw from the study at any time without prejudice. The study was approved by a competent Ethics Committee and covered by appropriate insurance.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Jul 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 81
    Country: Number of subjects enrolled
    United Kingdom: 54
    Country: Number of subjects enrolled
    Austria: 7
    Country: Number of subjects enrolled
    Germany: 18
    Country: Number of subjects enrolled
    Italy: 219
    Country: Number of subjects enrolled
    Japan: 80
    Country: Number of subjects enrolled
    Taiwan: 2
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 21
    Country: Number of subjects enrolled
    Switzerland: 19
    Country: Number of subjects enrolled
    Australia: 44
    Country: Number of subjects enrolled
    New Zealand: 4
    Worldwide total number of subjects
    549
    EEA total number of subjects
    325
    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)
    231
    From 65 to 84 years
    314
    85 years and over
    4

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Between October 3rd, 2018 and January 7th, 2022, 672 patients were screened for eligibility, and 551 patients from 89 centres were randomized (189 in Arm A and 360 in Arm B). Two patients were excluded from all analyses because of a lack of consent to use their data.

    Pre-assignment
    Screening details
    		 A total of 672 subjects were assessed for eligibility. Of these, 121 subjects were excluded prior to randomization: 86 subjects did not meet the eligibility criteria, 28 subjects withdrew informed consent, and 7 subjects were excluded for other reasons

    Period 1
    Period 1 title
    Overall Trial - ITT
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Blinding was ensured by identically packaged active and placebo IMP kits labeled with unique medication IDs. Emergency unblinding was managed through sealed envelopes stored securely at each site and opened only in case of medical emergency. Blinding was maintained after disease progression to allow unbiased assessment. Non-emergency unblinding required Sponsor approval and was considered a protocol deviation.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A
    Arm description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 6 or AUC 5 will be administered every 21 days for 6-8 cycles or PD. Placebo will be administered as I.V. infusion every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Placebo was administered every 3 weeks prior to carboplatin–paclitaxel and during the maintenance phase. The placebo was delivered by intravenous infusion in 250-mL 0.9% NaCl bags via PVC or polyolefin lines with 0.2 μm in-line filters. The first infusion was administered over 60 minutes, and if well tolerated, subsequent infusions were given over 30 minutes. Prepared solutions were used immediately or stored under specified conditions prior to infusion.

    Arm title
    		 ARM B
    Arm description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 5 or 6 will be administered every 21 days for 6-8 cycles or PD. Atezolizumab will be administered as I.V. infusion at a fixed dose of 1200 mg, every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).
    Arm type
    		 Experimental

    Investigational medicinal product name
    atezolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Atezolizumab was administered at a fixed dose of 1200 mg every 3 weeks, corresponding to an average weight-based dose of 15 mg/kg, prior to carboplatin–paclitaxel and during the maintenance phase. The drug was delivered by intravenous infusion in 250-mL 0.9% NaCl bags via PVC or polyolefin lines with 0.2 μm in-line filters. The first infusion was administered over 60 minutes, and if well tolerated, subsequent infusions were given over 30 minutes. Prepared solutions were used immediately or stored under specified conditions prior to infusion.

    Number of subjects in period 1
    		ARM A ARM B
    Started
    189
    360
    Completed
    108
    197
    Not completed
    81
    163
         Consent withdrawn by subject
    16
    16
         Lost to follow-up
    2
    6
         Treatment never administered
    4
    4
         Study closure
    59
    137
    Period 2
    Period 2 title
    ITT-dMMR
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A - dMMR
    Arm description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 6 or AUC 5 will be administered every 21 days for 6-8 cycles or PD. Placebo will be administered as I.V. infusion every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Placebo was administered every 3 weeks prior to carboplatin–paclitaxel and during the maintenance phase. The placebo was delivered by intravenous infusion in 250-mL 0.9% NaCl bags via PVC or polyolefin lines with 0.2 μm in-line filters. The first infusion was administered over 60 minutes, and if well tolerated, subsequent infusions were given over 30 minutes. Prepared solutions were used immediately or stored under specified conditions prior to infusion.

    Arm title
    		 ARM B - dMMR
    Arm description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 5 or 6 will be administered every 21 days for 6-8 cycles or PD. Atezolizumab will be administered as I.V. infusion at a fixed dose of 1200 mg, every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).
    Arm type
    		 Experimental

    Investigational medicinal product name
    atezolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Atezolizumab was administered at a fixed dose of 1200 mg every 3 weeks, corresponding to an average weight-based dose of 15 mg/kg, prior to carboplatin–paclitaxel and during the maintenance phase. The drug was delivered by intravenous infusion in 250-mL 0.9% NaCl bags via PVC or polyolefin lines with 0.2 μm in-line filters. The first infusion was administered over 60 minutes, and if well tolerated, subsequent infusions were given over 30 minutes. Prepared solutions were used immediately or stored under specified conditions prior to infusion.

    Number of subjects in period 2 [1]
    		ARM A - dMMR ARM B - dMMR
    Started
    44
    81
    Completed
    25
    29
    Not completed
    19
    52
         Consent withdrawn by subject
    3
    3
         Lost to follow-up
    1
    3
         Study closure
    15
    46
    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: The period option was used solely to define the analysis population for one of the primary endpoints. The periods do not represent consecutive study phases; therefore, the number of subjects starting this period is not expected to match the number completing the preceding period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 6 or AUC 5 will be administered every 21 days for 6-8 cycles or PD. Placebo will be administered as I.V. infusion every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).

    Reporting group title
    ARM B
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 5 or 6 will be administered every 21 days for 6-8 cycles or PD. Atezolizumab will be administered as I.V. infusion at a fixed dose of 1200 mg, every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).

    Reporting group values
    		 ARM A ARM B Total
    Number of subjects
    		 189 360 549
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    The age will be calculated as: Age(years)=year of randomization-year of birth,
    Units: years
        arithmetic mean (standard deviation)
    		 64.9 ( 9.5 ) 66.4 ( 8.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 189 360 549
    Subject analysis sets

    Subject analysis set title
    ITT-dMMR
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT-dMMR Analysis Set is defined as all participants with MSI/dMMR tumor who are included in the ITT Analysis set.

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT Analysis Set is defined as all participants who provide informed consent and are randomized in the study. Patients will be analysed according to the randomization arm, regardless the treatment actually received. The ITT Analysis Set is defined as all participants who provide informed consent and are randomized in the study. Patients will be analysed according to the randomization arm, regardless the treatment actually received.

    Subject analysis set title
    Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Analysis Set is defined as all patients included of the ITT Analysis Set, who receive at least one dose of study treatment, whether withdrawn prematurely or not. Patients will be considered in the treatment arm they actually received.

    Subject analysis sets values
    		 ITT-dMMR ITT Safety
    Number of subjects
    125
    549
    541
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    The age will be calculated as: Age(years)=year of randomization-year of birth,
    Units: years
        arithmetic mean (standard deviation)
    64.1 ( 9.7 )
    65.9 ( 9.1 )
    65.8 ( 9.1 )
    Gender categorical
    Units: Subjects
        Female
    125
    549
    541

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 6 or AUC 5 will be administered every 21 days for 6-8 cycles or PD. Placebo will be administered as I.V. infusion every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).

    Reporting group title
    ARM B
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 5 or 6 will be administered every 21 days for 6-8 cycles or PD. Atezolizumab will be administered as I.V. infusion at a fixed dose of 1200 mg, every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).
    Reporting group title
    ARM A - dMMR
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 6 or AUC 5 will be administered every 21 days for 6-8 cycles or PD. Placebo will be administered as I.V. infusion every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).

    Reporting group title
    ARM B - dMMR
    Reporting group description
    		 paclitaxel 175 mg/m2 + carboplatin AUC 5 or 6 will be administered every 21 days for 6-8 cycles or PD. Atezolizumab will be administered as I.V. infusion at a fixed dose of 1200 mg, every 21 days until objective radiological disease progression as assessed by the investigator if they do not meet any other discontinuation criteria (patient refusal, toxicity).

    Subject analysis set title
    ITT-dMMR
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT-dMMR Analysis Set is defined as all participants with MSI/dMMR tumor who are included in the ITT Analysis set.

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT Analysis Set is defined as all participants who provide informed consent and are randomized in the study. Patients will be analysed according to the randomization arm, regardless the treatment actually received. The ITT Analysis Set is defined as all participants who provide informed consent and are randomized in the study. Patients will be analysed according to the randomization arm, regardless the treatment actually received.

    Subject analysis set title
    Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Analysis Set is defined as all patients included of the ITT Analysis Set, who receive at least one dose of study treatment, whether withdrawn prematurely or not. Patients will be considered in the treatment arm they actually received.

    Primary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    The PFS is defined as the time from randomization to the date of first progression or death from any cause, whichever occurs first. The censored patients are patients alive and progression free at the time of statistical analysis (e.g. last tumor assessment without documented progression) or without information on the status (e.g. patients lost to follow-up without documented progression or death). For progressed or dead patients, the PFS time (months) is the time between the date of randomization and the date of first progression or death, whichever occurs first: PFS time(months)=(Date of progression or death -Date of randomization+1)/30.4
    End point type
    Primary
    End point timeframe
    overall trial
    End point values
    		 ARM A ARM B ARM A - dMMR ARM B - dMMR
    Number of subjects analysed
    189
    360
    44
    81
    Units: month
        median (confidence interval 95%)
    8.9 (8.1 to 9.6)
    9.9 (9.3 to 12.0)
    6.9 (6.2 to 9.0)
    0.0 (0.0 to 0.0)
    Statistical analysis title
    		 Logrank test ITT
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0055
    Method
    		 Logrank
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 4.22
    Statistical analysis title
    		 Logrank test ITT-dMMR
    Comparison groups
    ARM A - dMMR v ARM B - dMMR
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 0.55

    Primary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    The OS time (months) is the time between the date of randomization and the date of death or the last date in which the patient is known to be still alive: OS time(months)=(Date of death or Last follow‐up-Date of randomization+1)/30.4
    End point type
    Primary
    End point timeframe
    overall trial
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    189
    360
    Units: month
        median (confidence interval 95%)
    30.5 (25.0 to 41.8)
    36.0 (30.0 to 45.2)
    Statistical analysis title
    		 Logrank test ITT
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0824
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.1

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events and serious adverse events will be recorded from time of signature of first informed consent, throughout the treatment period and including the safety follow-up period (135 days after the last study drug administration).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26
    Reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 -

    Reporting group title
    ARM B
    Reporting group description
    		 -

    Serious adverse events
    		 ARM A ARM B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    63 / 185 (34.05%)
    137 / 356 (38.48%)
         number of deaths (all causes)
    108
    196
         number of deaths resulting from adverse events
    5
    11
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer stage 0
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal carcinoma
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    High-grade B-cell lymphoma
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Paraneoplastic syndrome
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lymphadenectomy
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device removal
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (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
    Asthenia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Mucosal inflammation
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 185 (0.54%)
    7 / 356 (1.97%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 185 (0.54%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Genital pain
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermenstrual bleeding
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    1 / 185 (0.54%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 185 (0.54%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal inflammation
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 185 (1.08%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         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 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteroides test positive
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         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 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    2 / 185 (1.08%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    2 / 185 (1.08%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (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 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac tamponade
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 185 (0.00%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinus node dysfunction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dural arteriovenous fistula
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 185 (2.70%)
    6 / 356 (1.69%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    5 / 185 (2.70%)
    16 / 356 (4.49%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 185 (0.54%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 185 (0.54%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 185 (0.00%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 185 (1.08%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 185 (0.54%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 185 (1.62%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 185 (0.54%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolonic fistula
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    5 / 185 (2.70%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Mechanical ileus
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 185 (0.54%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 185 (0.54%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 185 (0.54%)
    6 / 356 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 185 (0.54%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rash
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria papular
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 185 (0.54%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular disorder
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal vein thrombosis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 185 (0.00%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 185 (0.00%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    0 / 185 (0.00%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 185 (0.00%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Cellulitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 185 (1.08%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematological infection
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (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 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph gland infection
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 356 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 185 (1.08%)
    3 / 356 (0.84%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Pyelonephritis
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARS-CoV-2 sepsis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 185 (0.54%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma site infection
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    9 / 185 (4.86%)
    4 / 356 (1.12%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    2 / 185 (1.08%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 185 (1.08%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 356 (0.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 356 (0.28%)
         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
    		 ARM A ARM B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    185 / 185 (100.00%)
    351 / 356 (98.60%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 185 (6.49%)
    30 / 356 (8.43%)
         occurrences all number
    14
    37
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    13 / 185 (7.03%)
    17 / 356 (4.78%)
         occurrences all number
    18
    25
    Fatigue
         subjects affected / exposed
    76 / 185 (41.08%)
    139 / 356 (39.04%)
         occurrences all number
    107
    209
    Oedema peripheral
         subjects affected / exposed
    14 / 185 (7.57%)
    12 / 356 (3.37%)
         occurrences all number
    15
    13
    Pyrexia
         subjects affected / exposed
    20 / 185 (10.81%)
    55 / 356 (15.45%)
         occurrences all number
    29
    73
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    8 / 185 (4.32%)
    26 / 356 (7.30%)
         occurrences all number
    11
    28
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    7 / 185 (3.78%)
    18 / 356 (5.06%)
         occurrences all number
    8
    22
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 185 (5.95%)
    27 / 356 (7.58%)
         occurrences all number
    11
    32
    Dyspnoea
         subjects affected / exposed
    23 / 185 (12.43%)
    20 / 356 (5.62%)
         occurrences all number
    33
    23
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    11 / 185 (5.95%)
    31 / 356 (8.71%)
         occurrences all number
    13
    31
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    10 / 185 (5.41%)
    31 / 356 (8.71%)
         occurrences all number
    13
    43
    Aspartate aminotransferase increased
         subjects affected / exposed
    9 / 185 (4.86%)
    25 / 356 (7.02%)
         occurrences all number
    12
    30
    Blood creatinine increased
         subjects affected / exposed
    9 / 185 (4.86%)
    26 / 356 (7.30%)
         occurrences all number
    13
    36
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    8 / 185 (4.32%)
    29 / 356 (8.15%)
         occurrences all number
    10
    36
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    10 / 185 (5.41%)
    28 / 356 (7.87%)
         occurrences all number
    12
    28
    Headache
         subjects affected / exposed
    16 / 185 (8.65%)
    28 / 356 (7.87%)
         occurrences all number
    20
    34
    Paraesthesia
         subjects affected / exposed
    24 / 185 (12.97%)
    44 / 356 (12.36%)
         occurrences all number
    30
    64
    Peripheral sensory neuropathy
         subjects affected / exposed
    73 / 185 (39.46%)
    138 / 356 (38.76%)
         occurrences all number
    81
    156
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    65 / 185 (35.14%)
    147 / 356 (41.29%)
         occurrences all number
    92
    228
    Febrile neutropenia
         subjects affected / exposed
    7 / 185 (3.78%)
    23 / 356 (6.46%)
         occurrences all number
    9
    23
    Leukopenia
         subjects affected / exposed
    13 / 185 (7.03%)
    49 / 356 (13.76%)
         occurrences all number
    25
    122
    Neutropenia
         subjects affected / exposed
    73 / 185 (39.46%)
    145 / 356 (40.73%)
         occurrences all number
    145
    332
    Thrombocytopenia
         subjects affected / exposed
    50 / 185 (27.03%)
    102 / 356 (28.65%)
         occurrences all number
    69
    203
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    15 / 185 (8.11%)
    35 / 356 (9.83%)
         occurrences all number
    17
    40
    Constipation
         subjects affected / exposed
    50 / 185 (27.03%)
    98 / 356 (27.53%)
         occurrences all number
    66
    127
    Diarrhoea
         subjects affected / exposed
    35 / 185 (18.92%)
    80 / 356 (22.47%)
         occurrences all number
    46
    122
    Nausea
         subjects affected / exposed
    69 / 185 (37.30%)
    121 / 356 (33.99%)
         occurrences all number
    114
    193
    Stomatitis
         subjects affected / exposed
    17 / 185 (9.19%)
    36 / 356 (10.11%)
         occurrences all number
    19
    43
    Vomiting
         subjects affected / exposed
    15 / 185 (8.11%)
    51 / 356 (14.33%)
         occurrences all number
    23
    70
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    67 / 185 (36.22%)
    112 / 356 (31.46%)
         occurrences all number
    67
    116
    Pruritus
         subjects affected / exposed
    9 / 185 (4.86%)
    44 / 356 (12.36%)
         occurrences all number
    10
    51
    Rash
         subjects affected / exposed
    8 / 185 (4.32%)
    28 / 356 (7.87%)
         occurrences all number
    13
    41
    Rash maculo-papular
         subjects affected / exposed
    9 / 185 (4.86%)
    32 / 356 (8.99%)
         occurrences all number
    9
    48
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    6 / 185 (3.24%)
    21 / 356 (5.90%)
         occurrences all number
    8
    35
    Hypothyroidism
         subjects affected / exposed
    10 / 185 (5.41%)
    48 / 356 (13.48%)
         occurrences all number
    19
    67
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    51 / 185 (27.57%)
    94 / 356 (26.40%)
         occurrences all number
    81
    140
    Back pain
         subjects affected / exposed
    20 / 185 (10.81%)
    23 / 356 (6.46%)
         occurrences all number
    22
    27
    Myalgia
         subjects affected / exposed
    16 / 185 (8.65%)
    48 / 356 (13.48%)
         occurrences all number
    19
    69
    Pain in extremity
         subjects affected / exposed
    16 / 185 (8.65%)
    27 / 356 (7.58%)
         occurrences all number
    24
    32
    Infections and infestations
    COVID-19
         subjects affected / exposed
    19 / 185 (10.27%)
    37 / 356 (10.39%)
         occurrences all number
    21
    38
    Urinary tract infection
         subjects affected / exposed
    28 / 185 (15.14%)
    40 / 356 (11.24%)
         occurrences all number
    37
    58
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    23 / 185 (12.43%)
    39 / 356 (10.96%)
         occurrences all number
    26
    47
    Hypomagnesaemia
         subjects affected / exposed
    15 / 185 (8.11%)
    35 / 356 (9.83%)
         occurrences all number
    22
    47

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Jul 2018
    To include immune-related nephritis as an atezolizumab adverse reaction and its management guidelines, previously not addressed in the protocol, in line with updated safety information.
    20 Feb 2019
    To include immune-related myositis as an atezolizumab adverse reaction and its management guidelines. Additional updates were implemented to align clinical management with the current Investigator’s Brochure, formalize operational procedures in EDC/IVRS/IWRS, and extend the safety follow-up period to 135 days after last study drug administration, as requested by the German competent authority.
    09 Mar 2020
    To introduce exploratory analyses on PK, ADA and ct-DNA and to clarify eligibility criteria. Additional changes were made to update adverse reaction management per the current Investigator’s Brochure, allow surgery for patients becoming operable during the study, and better specify data collection and assessment timing.
    10 Feb 2021
    To update accrual duration and study timelines, introduce a revised statistical design anticipating PFS analysis at OS interim analysis, and add two futility analyses. Additional updates aligned adverse reaction management with the current Investigator’s Brochure and clarified procedures for AE reporting and emergency unblinding.
    03 May 2022
    To update clinical management guidelines for atezolizumab adverse reactions according to the latest Investigator’s Brochure and Dear Investigator Letters, and to update the study background and Statistical Analysis Plan.
    23 Apr 2024
    To update the protocol according to the evolving clinical and regulatory landscape, including new data on immune checkpoint inhibitors, updated approvals and safety information for atezolizumab, results of final PFS and interim OS analyses, post-trial access provisions, and updated scientific references.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/39102832
    http://www.ncbi.nlm.nih.gov/pubmed/40590326
    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-Sun Mar 22 12:09:03 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA