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   44237   clinical trials with a EudraCT protocol, of which   7338   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:
    An Adaptive Phase III, Multicenter, Randomized, Open-Label, Controlled Study of M7824 (bintrafusp alfa) versus Pembrolizumab as a First-line Treatment in Patients with PD-L1 Expressing Advanced Non-small Cell Lung Cancer

    Summary
    EudraCT number
    		 2018-001517-32
    Trial protocol
    		 DE   NL   BE   GR   ES   IT  
    Global end of trial date
    20 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Oct 2024
    First version publication date
    17 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MS200647_0037
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03631706
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    EMD Serono Research & Development Institute, Inc
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Communication Center, Merck KGaA,Darmstadt, Germany, +49 6151725200, service@merckgroup.com
    Scientific contact
    Communication Center, Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.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
    15 Oct 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jan 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study was to evaluate the efficacy and safety of bintrafusp alfa (M7824) compared with pembrolizumab in subjects with advanced Non-small Cell Lung Cancer (NSCLC) with high Programmed Death-ligand 1 (PD-L1)-tumor expression, with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation.
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Oct 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
    Argentina: 11
    Country: Number of subjects enrolled
    United States: 22
    Country: Number of subjects enrolled
    Belgium: 18
    Country: Number of subjects enrolled
    France: 25
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Netherlands: 12
    Country: Number of subjects enrolled
    Spain: 31
    Country: Number of subjects enrolled
    Türkiye: 21
    Country: Number of subjects enrolled
    Ukraine: 18
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    Brazil: 11
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    China: 19
    Country: Number of subjects enrolled
    Japan: 16
    Country: Number of subjects enrolled
    Korea, Republic of: 63
    Worldwide total number of subjects
    304
    EEA total number of subjects
    114
    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)
    113
    From 65 to 84 years
    183
    85 years and over
    8

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 152 participants were recruited in the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 M7824
    Arm description
    		 Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    M7824
    Investigational medicinal product code
    Other name
    Bintrafusp alfa
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Arm title
    		 Pembrolizumab
    Arm description
    		 Subjects received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous infusion of Pembrolizumab at a dose of200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Number of subjects in period 1
    		M7824 Pembrolizumab
    Started
    152
    152
    Treated
    152
    152
    Completed
    152
    152

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    M7824
    Reporting group description
    		 Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Subjects received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Reporting group values
    		 M7824 Pembrolizumab Total
    Number of subjects
    		 152 152 304
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 51 62 113
        From 65-84 years
    		 98 85 183
        85 years and over
    		 3 5 8
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 67 ( 9.56 ) 67 ( 10.17 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 42 36 78
        Male
    		 110 116 226
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 50 55 105
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 0 1
        White
    		 91 79 170
        Unknown or Not Reported
    		 7 14 21
        Other
    		 3 4 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 13 11 24
        Not Hispanic or Latino
    		 138 138 276
        Unknown or Not Reported
    		 1 3 4

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    M7824
    Reporting group description
    		 Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Subjects received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Primary: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC) [1]
    End point description
    Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Full analysis set included all subjects who were randomized to study intervention.
    End point type
    Primary
    End point timeframe
    Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
    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 and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 M7824 Pembrolizumab
    Number of subjects analysed
    152
    152
    Units: months
        median (full range (min-max))
    7.0 (0.0 to 19.4)
    11.1 (0.0 to 18.0)
    No statistical analyses for this end point

    Primary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS) [2]
    End point description
    Overall Survival was defined as the time from randomization of study intervention to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method. Full analysis set included all subjects who were randomized to study intervention.
    End point type
    Primary
    End point timeframe
    Time from randomization of study drug assessed approximately up to 843 days
    Notes
    [2] - 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 and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 M7824 Pembrolizumab
    Number of subjects analysed
    152
    152
    Units: months
        median (full range (min-max))
    21.1 (0.2 to 22.1)
    22.1 (0.1 to 26.4)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
    End point description
    Adverse Event (AE) was defined any untoward medical occurrence in a subject administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. Safety analysis set included all subjects who were administered at least one dose of M7824 or Pembrolizumab.
    End point type
    Secondary
    End point timeframe
    Time from first treatment assessed up to approximately 843 days
    End point values
    		 M7824 Pembrolizumab
    Number of subjects analysed
    151
    152
    Units: Subjects
        Subjects with any TEAE
    150
    145
        Subjects with any serious TEAE
    90
    61
        Subjects with any Treatment Related TEAEs
    124
    105
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

    		 Close Top of page
    End point title
    		 Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
    End point description
    DOR was defined for subjects with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates. Full analysis set included all subjects who were randomized to study intervention.
    End point type
    Secondary
    End point timeframe
    From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days
    End point values
    		 M7824 Pembrolizumab
    Number of subjects analysed
    71 [3]
    78 [4]
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (13.5 to 99999)
    Notes
    [3] - 99999 denotes no observation.
    [4] - 99999 denotes no observation.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
    End point description
    Percentage of subjects with unconfirmed best overall response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. Full analysis set included all subjects who were randomized to study intervention.
    End point type
    Secondary
    End point timeframe
    Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
    End point values
    		 M7824 Pembrolizumab
    Number of subjects analysed
    152
    152
    Units: percentage of subjects
        number (confidence interval 95%)
    46.7 (38.6 to 55.0)
    51.3 (43.1 to 59.5)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Time from first treatment assessed up to approximately 843 days
    Adverse event reporting additional description
    Safety analysis set included all subjects who were administered at least one dose of M7824 or Pembrolizumab.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    M7824
    Reporting group description
    		 Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Subjects received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.

    Serious adverse events
    		 M7824 Pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    90 / 151 (59.60%)
    61 / 152 (40.13%)
         number of deaths (all causes)
    49
    43
         number of deaths resulting from adverse events
    17
    10
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of skin
         subjects affected / exposed
    5 / 151 (3.31%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keratoacanthom
         subjects affected / exposed
    3 / 151 (1.99%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 151 (0.66%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (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
    Disease progression
         subjects affected / exposed
    6 / 151 (3.97%)
    7 / 152 (4.61%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 6
    0 / 5
    Death
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Asthenia
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 151 (1.99%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 151 (3.97%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    4 / 151 (2.65%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 151 (0.66%)
    3 / 152 (1.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    5 / 151 (3.31%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    3 / 151 (1.99%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Respiratory alkalosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Stridor
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 151 (1.32%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         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 / 151 (0.00%)
    1 / 152 (0.66%)
         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 / 151 (0.00%)
    1 / 152 (0.66%)
         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
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (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 / 151 (1.32%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation necrosis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Strangulated incisional hernia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Coronary artery disease
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (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
    Cerebrovascular accident
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated encephalitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 151 (2.65%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aplastic anaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune thrombocytopenia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Agranulocytosis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Immune-mediated enterocolitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune colitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         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 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lichen planus
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin toxicity
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic skin eruption
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 151 (0.00%)
    2 / 152 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated nephritis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenocorticotropic hormone deficiency
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture pain
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Spondylitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (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
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 151 (0.66%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (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
    9 / 151 (5.96%)
    12 / 152 (7.89%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 12
         deaths causally related to treatment / all
    0 / 2
    1 / 1
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         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
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 151 (1.32%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 151 (0.66%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 151 (1.99%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 151 (0.00%)
    1 / 152 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 151 (1.32%)
    3 / 152 (1.97%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 M7824 Pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    140 / 151 (92.72%)
    135 / 152 (88.82%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Keratoacanthoma
         subjects affected / exposed
    12 / 151 (7.95%)
    0 / 152 (0.00%)
         occurrences all number
    12
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    11 / 151 (7.28%)
    1 / 152 (0.66%)
         occurrences all number
    11
    1
    Hypertension
         subjects affected / exposed
    3 / 151 (1.99%)
    10 / 152 (6.58%)
         occurrences all number
    3
    10
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    14 / 151 (9.27%)
    13 / 152 (8.55%)
         occurrences all number
    14
    13
    Fatigue
         subjects affected / exposed
    30 / 151 (19.87%)
    26 / 152 (17.11%)
         occurrences all number
    30
    26
    Chest pain
         subjects affected / exposed
    8 / 151 (5.30%)
    6 / 152 (3.95%)
         occurrences all number
    8
    6
    Asthenia
         subjects affected / exposed
    26 / 151 (17.22%)
    30 / 152 (19.74%)
         occurrences all number
    26
    30
    Pyrexia
         subjects affected / exposed
    28 / 151 (18.54%)
    15 / 152 (9.87%)
         occurrences all number
    28
    15
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    23 / 151 (15.23%)
    22 / 152 (14.47%)
         occurrences all number
    23
    22
    Productive cough
         subjects affected / exposed
    7 / 151 (4.64%)
    11 / 152 (7.24%)
         occurrences all number
    7
    11
    Haemoptysis
         subjects affected / exposed
    27 / 151 (17.88%)
    6 / 152 (3.95%)
         occurrences all number
    27
    6
    Epistaxis
         subjects affected / exposed
    15 / 151 (9.93%)
    2 / 152 (1.32%)
         occurrences all number
    15
    2
    Dyspnoea
         subjects affected / exposed
    29 / 151 (19.21%)
    18 / 152 (11.84%)
         occurrences all number
    29
    18
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    16 / 151 (10.60%)
    10 / 152 (6.58%)
         occurrences all number
    16
    10
    Investigations
    Lipase increased
         subjects affected / exposed
    12 / 151 (7.95%)
    7 / 152 (4.61%)
         occurrences all number
    12
    7
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    19 / 151 (12.58%)
    16 / 152 (10.53%)
         occurrences all number
    19
    16
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    2 / 151 (1.32%)
    8 / 152 (5.26%)
         occurrences all number
    2
    8
    Blood creatinine increased
         subjects affected / exposed
    9 / 151 (5.96%)
    13 / 152 (8.55%)
         occurrences all number
    9
    13
    Blood bilirubin increased
         subjects affected / exposed
    9 / 151 (5.96%)
    3 / 152 (1.97%)
         occurrences all number
    9
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    18 / 151 (11.92%)
    11 / 152 (7.24%)
         occurrences all number
    18
    11
    Aspartate aminotransferase increased
         subjects affected / exposed
    23 / 151 (15.23%)
    14 / 152 (9.21%)
         occurrences all number
    23
    14
    Amylase increased
         subjects affected / exposed
    9 / 151 (5.96%)
    9 / 152 (5.92%)
         occurrences all number
    9
    9
    Alanine aminotransferase increased
         subjects affected / exposed
    19 / 151 (12.58%)
    16 / 152 (10.53%)
         occurrences all number
    19
    16
    Weight decreased
         subjects affected / exposed
    10 / 151 (6.62%)
    7 / 152 (4.61%)
         occurrences all number
    10
    7
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    12 / 151 (7.95%)
    8 / 152 (5.26%)
         occurrences all number
    12
    8
    Headache
         subjects affected / exposed
    14 / 151 (9.27%)
    14 / 152 (9.21%)
         occurrences all number
    14
    14
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    46 / 151 (30.46%)
    18 / 152 (11.84%)
         occurrences all number
    46
    18
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    14 / 151 (9.27%)
    10 / 152 (6.58%)
         occurrences all number
    14
    10
    Nausea
         subjects affected / exposed
    19 / 151 (12.58%)
    20 / 152 (13.16%)
         occurrences all number
    19
    20
    Diarrhoea
         subjects affected / exposed
    24 / 151 (15.89%)
    24 / 152 (15.79%)
         occurrences all number
    24
    24
    Constipation
         subjects affected / exposed
    16 / 151 (10.60%)
    22 / 152 (14.47%)
         occurrences all number
    16
    22
    Abdominal pain upper
         subjects affected / exposed
    3 / 151 (1.99%)
    8 / 152 (5.26%)
         occurrences all number
    3
    8
    Dyspepsia
         subjects affected / exposed
    5 / 151 (3.31%)
    11 / 152 (7.24%)
         occurrences all number
    5
    11
    Skin and subcutaneous tissue disorders
    Rash pruritic
         subjects affected / exposed
    8 / 151 (5.30%)
    5 / 152 (3.29%)
         occurrences all number
    8
    5
    Rash maculo-papular
         subjects affected / exposed
    17 / 151 (11.26%)
    6 / 152 (3.95%)
         occurrences all number
    17
    6
    Rash
         subjects affected / exposed
    48 / 151 (31.79%)
    25 / 152 (16.45%)
         occurrences all number
    48
    25
    Pruritus
         subjects affected / exposed
    52 / 151 (34.44%)
    42 / 152 (27.63%)
         occurrences all number
    52
    42
    Hyperkeratosis
         subjects affected / exposed
    8 / 151 (5.30%)
    0 / 152 (0.00%)
         occurrences all number
    8
    0
    Dry Skin
         subjects affected / exposed
    9 / 151 (5.96%)
    4 / 152 (2.63%)
         occurrences all number
    9
    4
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    17 / 151 (11.26%)
    23 / 152 (15.13%)
         occurrences all number
    17
    23
    Hyperthyroidism
         subjects affected / exposed
    6 / 151 (3.97%)
    10 / 152 (6.58%)
         occurrences all number
    6
    10
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    11 / 151 (7.28%)
    10 / 152 (6.58%)
         occurrences all number
    11
    10
    Back pain
         subjects affected / exposed
    8 / 151 (5.30%)
    13 / 152 (8.55%)
         occurrences all number
    8
    13
    Arthralgia
         subjects affected / exposed
    20 / 151 (13.25%)
    21 / 152 (13.82%)
         occurrences all number
    20
    21
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    11 / 151 (7.28%)
    4 / 152 (2.63%)
         occurrences all number
    11
    4
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 151 (5.96%)
    2 / 152 (1.32%)
         occurrences all number
    9
    2
    Pneumonia
         subjects affected / exposed
    8 / 151 (5.30%)
    21 / 152 (13.82%)
         occurrences all number
    8
    21
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    10 / 151 (6.62%)
    12 / 152 (7.89%)
         occurrences all number
    10
    12
    Hypomagnesaemia
         subjects affected / exposed
    4 / 151 (2.65%)
    8 / 152 (5.26%)
         occurrences all number
    4
    8
    Hypokalaemia
         subjects affected / exposed
    5 / 151 (3.31%)
    8 / 152 (5.26%)
         occurrences all number
    5
    8
    Hypoalbuminaemia
         subjects affected / exposed
    16 / 151 (10.60%)
    11 / 152 (7.24%)
         occurrences all number
    16
    11
    Hyperuricaemia
         subjects affected / exposed
    9 / 151 (5.96%)
    3 / 152 (1.97%)
         occurrences all number
    9
    3
    Hyperglycaemia
         subjects affected / exposed
    13 / 151 (8.61%)
    10 / 152 (6.58%)
         occurrences all number
    13
    10
    Decreased appetite
         subjects affected / exposed
    25 / 151 (16.56%)
    26 / 152 (17.11%)
         occurrences all number
    25
    26

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA