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    Clinical Trial Results:
    An Open-Label, Multi-Center, Safety Study of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies (STRONG) Module A – Post-Chemotherapy Urothelial and NonUrothelial Carcinoma of the Urinary Tract with Fixed-dose Durvalumab

    Summary
    EudraCT number
    2016-005068-33
    Trial protocol
    DE   GB   FR   IT  
    Global end of trial date
    16 Dec 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    28 Oct 2023
    First version publication date
    28 Oct 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D4191C00068
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03084471
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca Clinical study Information Center
    Sponsor organisation address
    Södertälje, Södertälje, Sweden, 151 85
    Public contact
    AstraZeneca Clinical study Information Center, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Jul 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality, including immune-relatedness, of adverse events (AEs) of special interest (AESIs) in patients with locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract (including the urinary bladder, ureter, urethra and renal pelvis) who were treated with a fixed-dose of durvalumab monotherapy.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation/Good Clinical Practice, applicable regulatory requirements, and the AstraZeneca policy on Bioethics and Human Biological Samples. Before enrollment of any patient into the study, the final protocol, including the final version of the informed consent form, was approved by the national regulatory authority or a notification to the national regulatory authority was done, according to local regulations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Apr 2017
    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
    Canada: 55
    Country: Number of subjects enrolled
    France: 468
    Country: Number of subjects enrolled
    Germany: 35
    Country: Number of subjects enrolled
    Italy: 210
    Country: Number of subjects enrolled
    Korea, Republic of: 61
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    867
    EEA total number of subjects
    717
    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)
    326
    From 65 to 84 years
    528
    85 years and over
    13

    Subject disposition

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    Recruitment
    Recruitment details
    Patients who met all the inclusion and none of the exclusion criteria were randomized at 77 study centers across 8 countries (Canada, France, Germany, Italy, Republic of Korea, Netherlands, United Kingdom and United States of America).

    Pre-assignment
    Screening details
    During the screening period (4 weeks), eligible patients signed the informed consent. All the study assessments were performed as per the schedule of assessment.

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

    Arms
    Arm title
    Durvalumab
    Arm description
    All patients received fixed-dose of durvalumab 1500 mg every 4 weeks until disease progression or unacceptable toxicity.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Durvalumab
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received 1500 mg durvalumab via intravenous (IV) infusion every 4 weeks (Q4W) until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

    Number of subjects in period 1
    Durvalumab
    Started
    867
    Completed
    0
    Not completed
    867
         Study specific discontinuation criteria
    2
         Consent withdrawn by subject
    12
         Other (as recorded)
    33
         Lack of therapeutic response
    2
         Adverse event, non-fatal
    73
         Condition under investigation worsened
    84
         Disease relapse
    181
         Subjective disease progression
    359
         Ongoing patients at data cut-off
    120
         Protocol deviation
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Durvalumab
    Reporting group description
    All patients received fixed-dose of durvalumab 1500 mg every 4 weeks until disease progression or unacceptable toxicity.

    Reporting group values
    Durvalumab Total
    Number of subjects
    867 867
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    326 326
        From 65-84 years
    528 528
        85 years and over
    13 13
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    67.5 ( 9.36 ) -
    Sex: Female, Male
    Units: Participants
        Female
    173 173
        Male
    694 694
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    65 65
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    2 2
        White
    508 508
        More than one race
    0 0
        Unknown or Not Reported
    264 264
        Other
    28 28

    End points

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    End points reporting groups
    Reporting group title
    Durvalumab
    Reporting group description
    All patients received fixed-dose of durvalumab 1500 mg every 4 weeks until disease progression or unacceptable toxicity.

    Subject analysis set title
    Adverse events of special interest (AESIs)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    AESIs are defined as AEs with a likely inflammatory or immune-mediated pathophysiological basis, resulting from the mechanism of action of durvalumab and/or tremelimumab and requiring more frequent monitoring and/or interventions, such as corticosteroids, immunosuppressants, and/or endocrine therapy.

    Subject analysis set title
    Adverse events of possible interest (AEPIs)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    AEPIs are defined as AEs that could have a potential inflammatory or immune-mediated pathophysiological basis, resulting from the mechanism of action of durvalumab but are more likely to have occurred due to other pathophysiological mechanisms, thus, the likelihood of the event being inflammatory or immune-mediated in nature is not high and/or is most often or usually explained by the other causes.

    Subject analysis set title
    Immune-mediated adverse events (imAEs)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The imAEs that occurred during this study were determined by a programmatic algorithm that required specific treatment for AESIs to be considered imAEs; the same specific treatment was required for AEPIs as well.

    Primary: Number of patients with adverse events of special interest (AESIs), adverse events of possible interest (AEPIs) and immune-mediated adverse events (imAEs)

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    End point title
    Number of patients with adverse events of special interest (AESIs), adverse events of possible interest (AEPIs) and immune-mediated adverse events (imAEs) [1]
    End point description
    Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of adverse events of special interest (AESIs) were assessed. AESIs included events with a potential inflammatory or immune-mediated mechanism that required interventions such as steroids, immunosuppressants, and/or hormone replacement therapy. Serious adverse event (SAE); Common Terminology Criteria for Adverse Events (CTCAE); Investigational product (IP). Safety analysis set: all enrolled participants who received at least one dose of durvalumab.
    End point type
    Primary
    End point timeframe
    From screening to safety follow up visit (90 days after last dose), up to approximately 3 years.
    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
    Adverse events of special interest (AESIs) Adverse events of possible interest (AEPIs) Immune-mediated adverse events (imAEs)
    Number of subjects analysed
    867
    867
    867
    Units: Patients
        Any adverse event (AE)
    265
    300
    97
        Any AE of CTCAE Grade 3 or 4
    21
    49
    17
        Any SAE (events outcome = death)
    19
    13
    11
        Any AE with outcome = death
    1
    0
    0
        Any AE, related to IP
    191
    145
    87
        Any AE of CTCAE Grade 3 or 4, related to IP
    15
    20
    16
        Any SAE, related to treatment
    14
    3
    10
        Any AE with outcome = death, related to IP
    1
    0
    0
        Any AE leading to discontinuation of IP
    12
    7
    10
        Event outcome resolved
    140
    119
    32
        Event outcome not resolved
    124
    181
    65
    No statistical analyses for this end point

    Secondary: Overall survival

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    End point title
    Overall survival
    End point description
    Overall survival was defined as the time from the first date of treatment until death due to any cause. Safety analysis set: all enrolled participants who received at least 1 dose of durvalumab.
    End point type
    Secondary
    End point timeframe
    From screening to final data cutoff (maximum up to 4 years) following date of first patient treatment initiation.
    End point values
    Durvalumab
    Number of subjects analysed
    867
    Units: Months
        median (confidence interval 95%)
    7.0 (6.44 to 8.18)
    No statistical analyses for this end point

    Secondary: Number of patients with adverse events

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    End point title
    Number of patients with adverse events
    End point description
    Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent AEs (including SAEs) was assessed. Safety analysis set: all enrolled participants who received at least one dose of durvalumab.
    End point type
    Secondary
    End point timeframe
    From screening to safety follow up visit (90 days after last dose), maximum up to 4 years.
    End point values
    Durvalumab
    Number of subjects analysed
    867
    Units: Patients
        Any AE
    787
        Any AE related to IP
    407
        Any AE of CTCAE grade 3 or higher
    365
        Any AE of CTCAE grade 3 or higher, related to IP
    78
        Any AE with outcome = death
    42
        Any AE with outcome = death related to IP
    9
        Any SAE (including events with outcome = death)
    254
        Any SAE (events outcome = death) related to IP
    41
        Any AE leading to discontinuation of IP
    77
        IP-related AE leading to discontinuation
    33
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From screening to safety follow up visit (90 days after last dose), maximum up to 4 years.
    Adverse event reporting additional description
    MedDRA version 23.0
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Durvalumab
    Reporting group description
    All participants received fixed-dose of durvalumab 1500 mg every 4 weeks until disease progression or unacceptable toxicity.

    Serious adverse events
    Durvalumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    254 / 867 (29.30%)
         number of deaths (all causes)
    600
         number of deaths resulting from adverse events
    43
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour hyperprogression
         subjects affected / exposed
    11 / 867 (1.27%)
         occurrences causally related to treatment / all
    10 / 11
         deaths causally related to treatment / all
    7 / 8
    Basal cell carcinoma
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infected neoplasm
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic neoplasm
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Tumour pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Shock haemorrhagic
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Deep vein thrombosis
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphoedema
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    7 / 867 (0.81%)
         occurrences causally related to treatment / all
    1 / 7
         deaths causally related to treatment / all
    0 / 3
    Death
         subjects affected / exposed
    5 / 867 (0.58%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    Pyrexia
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Asthenia
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Drug intolerance
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperthermia malignant
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Scrotal mass
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    7 / 867 (0.81%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    Dyspnoea
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Lung disorder
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural thickening
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Delirium
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Device dislocation
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stent malfunction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    5 / 867 (0.58%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Femur fracture
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Postoperative ileus
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stomal hernia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Urinary tract stoma complication
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    Pericardial effusion
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiac arrest
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Coronary artery occlusion
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Basilar artery occlusion
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Embolic stroke
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frontal lobe epilepsy
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peroneal nerve palsy
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VIth nerve disorder
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Anaemia
         subjects affected / exposed
    6 / 867 (0.69%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    7 / 867 (0.81%)
         occurrences causally related to treatment / all
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
         subjects affected / exposed
    5 / 867 (0.58%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Subileus
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Autoimmune colitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Duodenitis haemorrhagic
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Intestinal atony
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Intestinal pseudo-obstruction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    5 / 867 (0.58%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hepatocellular injury
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatitis
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    7 / 867 (0.81%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    8 / 867 (0.92%)
         occurrences causally related to treatment / all
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Urine abnormality
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Urinary tract inflammation
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypophysitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    7 / 867 (0.81%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    8 / 867 (0.92%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    17 / 867 (1.96%)
         occurrences causally related to treatment / all
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    18 / 867 (2.08%)
         occurrences causally related to treatment / all
    0 / 20
         deaths causally related to treatment / all
    0 / 5
    Urosepsis
         subjects affected / exposed
    5 / 867 (0.58%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Pneumonia
         subjects affected / exposed
    6 / 867 (0.69%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    COVID-19
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Clostridium colitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterobacter infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterobacter sepsis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatitis E
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Cellulitis
         subjects affected / exposed
    2 / 867 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bacterial infection
         subjects affected / exposed
    3 / 867 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    4 / 867 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Tracheitis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    1 / 867 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Durvalumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    669 / 867 (77.16%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    48 / 867 (5.54%)
         occurrences all number
    54
    Weight decreased
         subjects affected / exposed
    46 / 867 (5.31%)
         occurrences all number
    48
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    228 / 867 (26.30%)
         occurrences all number
    250
    Pyrexia
         subjects affected / exposed
    79 / 867 (9.11%)
         occurrences all number
    92
    Oedema peripheral
         subjects affected / exposed
    75 / 867 (8.65%)
         occurrences all number
    79
    Fatigue
         subjects affected / exposed
    83 / 867 (9.57%)
         occurrences all number
    96
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    172 / 867 (19.84%)
         occurrences all number
    186
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    171 / 867 (19.72%)
         occurrences all number
    190
    Diarrhoea
         subjects affected / exposed
    136 / 867 (15.69%)
         occurrences all number
    173
    Nausea
         subjects affected / exposed
    126 / 867 (14.53%)
         occurrences all number
    141
    Vomiting
         subjects affected / exposed
    76 / 867 (8.77%)
         occurrences all number
    86
    Abdominal pain
         subjects affected / exposed
    64 / 867 (7.38%)
         occurrences all number
    73
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    84 / 867 (9.69%)
         occurrences all number
    91
    Dyspnoea
         subjects affected / exposed
    74 / 867 (8.54%)
         occurrences all number
    81
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    109 / 867 (12.57%)
         occurrences all number
    142
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    64 / 867 (7.38%)
         occurrences all number
    77
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    57 / 867 (6.57%)
         occurrences all number
    64
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    82 / 867 (9.46%)
         occurrences all number
    84
    Arthralgia
         subjects affected / exposed
    65 / 867 (7.50%)
         occurrences all number
    75
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    84 / 867 (9.69%)
         occurrences all number
    95
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    149 / 867 (17.19%)
         occurrences all number
    156

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2017
    Version 2: AEs that met criteria for IP discontinuation were updated following updated Toxicity Management Guidelines.
    19 Apr 2017
    Version 3: Screening and other assessments were updated to align with new durvalumab+/-tremelimumab protocol template.This includes clarification /corrections of urinalysis, vital signs, and weight/height. Exclusion criteria were updated to include patients who had adequate organ or marrow function irrespective of dependence on transfusion or growth factor support. An option to collect tumor tissue was added in case an archival sample was not available and patient consented to sample collection.
    08 Feb 2018
    Version 4: Inclusion and exclusion criteria were updated to align with the new durvalumab+/-tremelimumab protocol template. Additional inflammatory responses were added to AESIs to align with the updated Investigator’s brochure. Removal of redundant procedure (height was not needed at baseline as well as screening).
    13 Dec 2019
    Version 5: Safety (AESIs) and risks were updated to align with durvalumab IB and tremelimumab IB. The protocol deviation related to infusion time < 55 minutes was removed to align with the durvalumab+/-tremelimumab protocol template. Overall study duration (clarified as 4 to 5 years), dates/duration for survival follow-up, deletion of specific instructions for immune-mediated adverse event (imAE) follow-up, clarification of SAE reporting and collection of safety data for patients who continued receiving treatment once the final data cut-off (DCO) is reached, and duration of treatment and criteria for treatment through progression and for retreatment. Exclusion criterion 4 was corrected to state that participation in another clinical study with an IP during the last 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment. New malignant tumors were added as a category of SAEs.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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