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    Clinical Trial Results:
    A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer

    Summary
    EudraCT number
    		 2018-003265-34
    Trial protocol
    		 FR   DE   BE   NL   ES   HU   NO  
    Global end of trial date
    17 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Dec 2023
    First version publication date
    21 Dec 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MS200647_0005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03840902
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Healthcare KGaA, Darmstadt, Germany
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Communication Centre, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
    Scientific contact
    Communication Centre, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.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
    17 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Feb 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main purpose of this study was to evaluate safety and efficacy in subjects treated with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT plus placebo followed by durvalumab.
    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
    16 Apr 2019
    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: 2
    Country: Number of subjects enrolled
    United States: 9
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Poland: 3
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Türkiye: 28
    Country: Number of subjects enrolled
    Taiwan: 5
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Brazil: 8
    Country: Number of subjects enrolled
    China: 18
    Country: Number of subjects enrolled
    Japan: 27
    Country: Number of subjects enrolled
    Korea, Republic of: 9
    Country: Number of subjects enrolled
    Russian Federation: 3
    Worldwide total number of subjects
    153
    EEA total number of subjects
    34
    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)
    70
    From 65 to 84 years
    82
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 First subject signed informed consent: 16-Apr-2019, Clinical data cut-off: 21-Jul-2021.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 cCRT plus M7824 followed by M7824
    Arm description
    		 Subjects received Concomitant Chemoradiotherapy (cCRT): Cisplatin/Etoposide [(50 milligrams per square meter (mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel (carboplatin intravenously based on area under curve (AUC) 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed (50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with Intensity Modulated Radiation Therapy 5 (IMRT 5), fractions per week for about 6 weeks (Total 60 gray [Gy]) in combination with intravenous infusion of 1200 mg of M7824 every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In combination with etoposide, subjects received cisplatin 50 mg/m^2 intravenously on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, subjects received cisplatin 75 mg/m2 intravenously on Days 1, 22, and 43 during cCRT.

    Investigational medicinal product name
    carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received carboplatin intravenously based on area under curve (AUC) 2 on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

    Investigational medicinal product name
    M7824
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous infusion of 1200 mg of M7824 q2w during cCRT.

    Investigational medicinal product name
    pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received pemetrexed at a dose of 500 mg/m^2 intravenously on Days 1, 22, and 43 during cCRT.

    Investigational medicinal product name
    IMRT 5
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion, Radiopharmaceutical precursor
    Routes of administration
    Intravenous use, Not mentioned
    Dosage and administration details
    Subjects received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received etoposide 50 mg/m^2 intravenously daily on Day 1 to 5 and Day 29 to 33 during cCRT.

    Investigational medicinal product name
    paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received paclitaxel intravenously at a dose of 45 mg/m^2 on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

    Arm title
    		 cCRT plus Placebo followed by Durvalumab
    Arm description
    		 Subjects received cCRT: Cisplatin/Etoposide [(50 mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel, carboplatin intravenously based on AUC 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed, 50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with IMRT 5, Total 60 gy in combination with intravenous infusion of placebo matched to M7824 over 1 hour Q2W during cCRT followed by intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) Q2W up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion, Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In combination with etoposide, subjects received cisplatin 50 mg/m^2 intravenously on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, subjects received cisplatin 75 mg/m2 intravenously on Days 1, 22, and 43 during cCRT.

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received etoposide 50 mg/m^2 intravenously daily on Day 1 to 5 and Day 29 to 33 during cCRT.

    Investigational medicinal product name
    carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received carboplatin intravenously based on area under curve (AUC) 2 on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

    Investigational medicinal product name
    paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received paclitaxel intravenously at a dose of 45 mg/m^2 on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

    Investigational medicinal product name
    pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received pemetrexed at a dose of 500 mg/m^2 intravenously on Days 1, 22, and 43 during cCRT.

    Investigational medicinal product name
    IMRT 5
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion, Radiopharmaceutical precursor
    Routes of administration
    Intravenous use, Not mentioned
    Dosage and administration details
    Subjects received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous infusion of placebo matched to M7824 q2w during cCRT.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous infusion of durvalumab 10 mg/kg q2w up to 1 year.

    Number of subjects in period 1
    		cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Started
    75
    78
    Treated
    74
    77
    Completed
    74
    77
    Not completed
    1
    1
         Randomized but not treated
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    cCRT plus M7824 followed by M7824
    Reporting group description
    		 Subjects received Concomitant Chemoradiotherapy (cCRT): Cisplatin/Etoposide [(50 milligrams per square meter (mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel (carboplatin intravenously based on area under curve (AUC) 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed (50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with Intensity Modulated Radiation Therapy 5 (IMRT 5), fractions per week for about 6 weeks (Total 60 gray [Gy]) in combination with intravenous infusion of 1200 mg of M7824 every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

    Reporting group title
    cCRT plus Placebo followed by Durvalumab
    Reporting group description
    		 Subjects received cCRT: Cisplatin/Etoposide [(50 mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel, carboplatin intravenously based on AUC 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed, 50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with IMRT 5, Total 60 gy in combination with intravenous infusion of placebo matched to M7824 over 1 hour Q2W during cCRT followed by intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) Q2W up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

    Reporting group values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab Total
    Number of subjects
    		 75 78 153
    Age categorical
    Units: Subjects
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 64.7 ( 9.35 ) 64.9 ( 8.94 ) -
    Sex: Female, Male
    Units: subjects
        Female
    		 20 16 36
        Male
    		 55 62 117
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 25 34 59
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 0 1
        White
    		 48 41 89
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 1 3 4
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 5 3 8
        Not Hispanic or Latino
    		 70 74 144
        Unknown or Not Reported
    		 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    cCRT plus M7824 followed by M7824
    Reporting group description
    		 Subjects received Concomitant Chemoradiotherapy (cCRT): Cisplatin/Etoposide [(50 milligrams per square meter (mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel (carboplatin intravenously based on area under curve (AUC) 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed (50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with Intensity Modulated Radiation Therapy 5 (IMRT 5), fractions per week for about 6 weeks (Total 60 gray [Gy]) in combination with intravenous infusion of 1200 mg of M7824 every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

    Reporting group title
    cCRT plus Placebo followed by Durvalumab
    Reporting group description
    		 Subjects received cCRT: Cisplatin/Etoposide [(50 mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel, carboplatin intravenously based on AUC 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed, 50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with IMRT 5, Total 60 gy in combination with intravenous infusion of placebo matched to M7824 over 1 hour Q2W during cCRT followed by intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) Q2W up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

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

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    End point title
    		 Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator [1]
    End point description
    PFS was defined as the time from randomization to the date of 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. PFS was analyzed by using the Kaplan-Meier method. Full Analysis Set (FAS) included all subjects who were randomized to study treatment.
    End point type
    Primary
    End point timeframe
    Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months
    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: Only descriptive statistics was planned for this endpoint.
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    75
    78
    Units: months
        median (full range (min-max))
    3.7 (1.9 to 5.6)
    3.7 (1.8 to 3.9)
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events

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    End point title
    		 Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events
    End point description
    Adverse Event (AE) was defined any untoward medical occurrence in a subject administered with a study drug, which does not necessarily have 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 (SAF) Analysis Set included all subjects who were administered any dose of any study intervention.
    End point type
    Secondary
    End point timeframe
    Time from randomization up to data cut off (assessed up to 27 months)
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    74
    77
    Units: subjects
        TEAEs
    70
    74
        Immunotherapy related TEAE
    48
    48
        Cisplatin/etoposide chemotherapy related TEAE
    7
    11
        Carboplatin/paclitaxel chemotherapy related TEAE
    46
    47
        Cisplatin/pemetrexed chemotherapy related TEAE
    15
    11
        Radiotherapy related TEAE
    59
    60
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall Survival was defined as the time from randomization to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method. FAS included all subjects who were randomized to study treatment.
    End point type
    Secondary
    End point timeframe
    Time from randomization to the date of death due to any cause, assessed up to 27 months
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    75
    78
    Units: months
        median (full range (min-max))
    4.6 (0.1 to 22.3)
    4.3 (0.3 to 22.7)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

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    End point title
    		 Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
    End point description
    ORR was defined as the percentage of subjects who had achieved complete response (CR) or partial response (PR) as the best overall response according to RECIST v1.1as adjudicated by the Investigator. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions. FAS included all subjects who were randomized to study treatment.
    End point type
    Secondary
    End point timeframe
    Time from randomization up to data cut off (assessed up to 27 months)
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    75
    78
    Units: percentage of subjects
        number (confidence interval 95%)
    29.3 (19.4 to 41.0)
    32.1 (21.9 to 43.6)
    No statistical analyses for this end point

    Secondary: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824

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    End point title
    		 Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824
    End point description
    Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed M7824 concentration-time data. Based on recommendations by an external Independent Data Monitoring Committee (IDMC), Sponsor decided to discontinue this clinical study. Subsequently, the data for this outcome measure was not collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    0 [2]
    0 [3]
    Units: microgram per milliliter (mcg/mL)
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    Notes
    [2] - Data was not collected and analyzed.
    [3] - Data was not collected and analyzed.
    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 Investigator

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    End point title
    		 Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
    End point description
    DOR was defined for subjects with confirmed 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.
    End point type
    Secondary
    End point timeframe
    Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed approximately up to 27 months
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: subjects
    Notes
    [4] - Due to early termination of the study, the data for this outcome measure was not collected.
    [5] - Due to early termination of the study, the data for this outcome measure was not collected.
    No statistical analyses for this end point

    Secondary: Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824

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    End point title
    		 Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824
    End point description
    Ctrough was the serum concentration observed immediately before next dosing. Based on recommendations by an external Independent Data Monitoring Committee (IDMC), Sponsor decided to discontinue this clinical study. Subsequently, the data for this outcome measure was not collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: mcg/mL
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    Notes
    [6] - Data was not collected and analyzed.
    [7] - Data was not collected and analyzed.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Antidrug Antibodies (ADA)

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    End point title
    		 Number of Subjects With Positive Antidrug Antibodies (ADA)
    End point description
    Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of subjects with positive ADA were reported. Based on recommendations by an external Independent Data Monitoring Committee (IDMC), Sponsor decided to discontinue this clinical study. Subsequently, the data for this outcome measure was not collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Time from randomization up to data cut off (assessed up to 27 months)
    End point values
    		 cCRT plus M7824 followed by M7824 cCRT plus Placebo followed by Durvalumab
    Number of subjects analysed
    0 [8]
    0 [9]
    Units: subjects
        number (not applicable)
    Notes
    [8] - Data was not collected and analyzed.
    [9] - Data was not collected and analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Time from randomization up to data cut off (assessed up to 27 months)
    Adverse event reporting additional description
    Safety (SAF) Analysis Set included all participants who were administered any dose of any study intervention.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    cCRT plus Placebo followed by Durvalumab
    Reporting group description
    		 Subjects received cCRT: Cisplatin/Etoposide [(50 mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel, carboplatin intravenously based on AUC 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed, 50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with IMRT 5, Total 60 gy in combination with intravenous infusion of placebo matched to M7824 over 1 hour Q2W during cCRT followed by intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) Q2W up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

    Reporting group title
    cCRT plus M7824 followed by M7824
    Reporting group description
    		 Subjects received Concomitant Chemoradiotherapy (cCRT): Cisplatin/Etoposide [(50 milligrams per square meter (mg/m^2) of Cisplatin intravenously on Days 1, 8, 29, and 36 with 50 mg/m^2 intravenously of Etoposide daily on Days 1 to 5 and Days 29 to 33 during cCRT]; Carboplatin/Paclitaxel (carboplatin intravenously based on area under curve (AUC) 2 on Days 1, 8, 15, 22, 29, 36, and 43 with 45 mg/m^2 of Paclitaxel on Days 1, 8, 15, 22, 29, 36, and 43 during cCRT; Cisplatin/Pemetrexed (50 mg/m^2 of Cisplatin intravenously on Days 1, 8, 29, and 36 with 500 mg/m^2 of Pemetrexed intravenously on Days 1, 22, and 43 during cCRT concomitant with Intensity Modulated Radiation Therapy 5 (IMRT 5), fractions per week for about 6 weeks (Total 60 gray [Gy]) in combination with intravenous infusion of 1200 mg of M7824 every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

    Serious adverse events
    		 cCRT plus Placebo followed by Durvalumab cCRT plus M7824 followed by M7824
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 77 (40.26%)
    43 / 74 (58.11%)
         number of deaths (all causes)
    5
    13
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bowen's disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Disease progression
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pyrexia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Immune system disorders
    Contrast media allergy
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    5 / 74 (6.76%)
         occurrences causally related to treatment / all
    6 / 9
    5 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated lung disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiccups
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Atelectasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Bronchial haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Dyspnoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerular filtration rate decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation mucositis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation oesophagitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrioventricular block complete
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Myocardial infarction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Neuropathy peripheral
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic outlet syndrome
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    4 / 74 (5.41%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal vascular malformation haemorrhagic
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    5 / 74 (6.76%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Immune-mediated hepatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pemphigoid
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema multiforme
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         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
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Parainfluenzae virus infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumonia bacterial
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Sepsis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Urinary tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypocalcaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 cCRT plus Placebo followed by Durvalumab cCRT plus M7824 followed by M7824
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    72 / 77 (93.51%)
    68 / 74 (91.89%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Keratoacanthoma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    4 / 74 (5.41%)
         occurrences all number
    0
    5
    Leukaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Skin papilloma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Vascular disorders
    Phlebitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Orthostatic hypotension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Intermittent claudication
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Phlebitis superficial
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hypertension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    3 / 74 (4.05%)
         occurrences all number
    2
    3
    Deep vein thrombosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Hypotension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    4 / 74 (5.41%)
         occurrences all number
    5
    4
    General disorders and administration site conditions
    Chills
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 74 (1.35%)
         occurrences all number
    4
    1
    Asthenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    13 / 74 (17.57%)
         occurrences all number
    6
    19
    Catheter site pruritus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Chest discomfort
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Chest pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Fatigue
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    14 / 77 (18.18%)
    5 / 74 (6.76%)
         occurrences all number
    15
    5
    Gait disturbance
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Generalised oedema
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Hyperthermia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Infusion site extravasation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Infusion site reaction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Malaise
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    5 / 74 (6.76%)
         occurrences all number
    6
    6
    Mucosal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Mucosal inflammation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    5 / 74 (6.76%)
         occurrences all number
    3
    6
    Oedema peripheral
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Pyrexia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 77 (12.99%)
    18 / 74 (24.32%)
         occurrences all number
    11
    22
    Feeling hot
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Breast pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Erectile dysfunction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Erection increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Bronchitis chronic
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    13 / 74 (17.57%)
         occurrences all number
    2
    16
    Respiratory distress
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Dyspnoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    3 / 74 (4.05%)
         occurrences all number
    7
    4
    Dysphonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Cough
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    14 / 77 (18.18%)
    15 / 74 (20.27%)
         occurrences all number
    16
    15
    Chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Haemoptysis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    7 / 74 (9.46%)
         occurrences all number
    3
    9
    Hiccups
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    6 / 74 (8.11%)
         occurrences all number
    6
    9
    Hypoxia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Interstitial lung disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    3
    Oropharyngeal pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    2 / 74 (2.70%)
         occurrences all number
    3
    2
    Pleural effusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Pleurisy
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Pneumonitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 77 (12.99%)
    4 / 74 (5.41%)
         occurrences all number
    12
    4
    Pneumothorax
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Productive cough
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    4 / 74 (5.41%)
         occurrences all number
    3
    6
    Pulmonary embolism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    2 / 74 (2.70%)
         occurrences all number
    2
    2
    Dyspnoea exertional
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Rhinorrhoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Anxiety
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Anxiety disorder
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Delirium
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Depression
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Insomnia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    9 / 77 (11.69%)
    9 / 74 (12.16%)
         occurrences all number
    11
    10
    Product issues
    Device malfunction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Alanine aminotransferase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    9 / 77 (11.69%)
    6 / 74 (8.11%)
         occurrences all number
    11
    10
    Alpha hydroxybutyrate dehydrogenase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Amylase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    5 / 74 (6.76%)
         occurrences all number
    3
    11
    Anti-transglutaminase antibody increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    6 / 74 (8.11%)
         occurrences all number
    11
    7
    Blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    3
    0
    Blood bilirubin increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    3 / 74 (4.05%)
         occurrences all number
    5
    4
    Blood cholesterol increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 74 (1.35%)
         occurrences all number
    4
    1
    Blood creatine increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    4 / 74 (5.41%)
         occurrences all number
    2
    8
    Blood creatinine increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 74 (5.41%)
         occurrences all number
    4
    4
    Blood glucose increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    3
    Blood lactate dehydrogenase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    2
    Blood thyroid stimulating hormone increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Blood triglycerides increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Blood urea increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    2 / 74 (2.70%)
         occurrences all number
    9
    5
    Brain natriuretic peptide increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    C-reactive protein increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    2
    Transaminases increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    5 / 74 (6.76%)
         occurrences all number
    13
    7
    Gastric pH decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Glomerular filtration rate decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    2
    Hepatic enzyme increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Lipase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    8 / 74 (10.81%)
         occurrences all number
    1
    9
    Lung diffusion test decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Lymphocyte count decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    13 / 77 (16.88%)
    11 / 74 (14.86%)
         occurrences all number
    23
    16
    Neutrophil count decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    20 / 77 (25.97%)
    17 / 74 (22.97%)
         occurrences all number
    36
    28
    Platelet count decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    13 / 77 (16.88%)
    11 / 74 (14.86%)
         occurrences all number
    21
    16
    Procalcitonin increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Protein total decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Prothrombin time prolonged
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    2
    Pulmonary function test decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    SARS-CoV-2 test positive
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Total bile acids increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Fibrin D dimer increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    White blood cell count increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    White blood cell count decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    29 / 77 (37.66%)
    24 / 74 (32.43%)
         occurrences all number
    59
    37
    Weight increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Weight decreased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    8 / 77 (10.39%)
    8 / 74 (10.81%)
         occurrences all number
    8
    9
    Injury, poisoning and procedural complications
    Fall
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Fibula fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Infusion related reaction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    2 / 74 (2.70%)
         occurrences all number
    3
    2
    Pelvic fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Radiation fibrosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Radiation fibrosis - lung
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Radiation mucositis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Radiation oesophagitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    13 / 77 (16.88%)
    13 / 74 (17.57%)
         occurrences all number
    15
    13
    Radiation pneumonitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    9 / 77 (11.69%)
    7 / 74 (9.46%)
         occurrences all number
    12
    7
    Radiation skin injury
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 77 (12.99%)
    5 / 74 (6.76%)
         occurrences all number
    10
    5
    Spinal compression fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Thermal burn
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina pectoris
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    3
    Supraventricular extrasystoles
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Myocardial ischaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Palpitations
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Pericardial effusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Sinus tachycardia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Atrial fibrillation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 74 (2.70%)
         occurrences all number
    1
    2
    Supraventricular tachycardia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Nervous system disorders
    Tremor
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Cerebral microhaemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Dizziness
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    3 / 74 (4.05%)
         occurrences all number
    5
    3
    Syncope
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Somnolence
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Peripheral sensory neuropathy
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Neuropathy peripheral
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 74 (2.70%)
         occurrences all number
    1
    2
    Headache
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 74 (2.70%)
         occurrences all number
    5
    2
    Dysgeusia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 74 (2.70%)
         occurrences all number
    1
    2
    Dizziness postural
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Dizziness exertional
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    32 / 77 (41.56%)
    38 / 74 (51.35%)
         occurrences all number
    53
    49
    Febrile neutropenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Lymphopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 74 (5.41%)
         occurrences all number
    3
    4
    Leukopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 77 (12.99%)
    9 / 74 (12.16%)
         occurrences all number
    12
    13
    Iron deficiency anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Neutropenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    15 / 77 (19.48%)
    20 / 74 (27.03%)
         occurrences all number
    18
    27
    Pancytopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Thrombocytopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    11 / 74 (14.86%)
         occurrences all number
    8
    16
    Ear and labyrinth disorders
    Ear pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    0 / 74 (0.00%)
         occurrences all number
    3
    0
    Abdominal pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Gingival pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Abdominal rigidity
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Anal fissure
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Ascites
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Colitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    3 / 74 (4.05%)
         occurrences all number
    1
    3
    Constipation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    34 / 77 (44.16%)
    23 / 74 (31.08%)
         occurrences all number
    43
    26
    Dental caries
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Diarrhoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    12 / 77 (15.58%)
    12 / 74 (16.22%)
         occurrences all number
    13
    14
    Dry mouth
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences all number
    0
    3
    Dyspepsia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    5 / 74 (6.76%)
         occurrences all number
    4
    5
    Dysphagia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    9 / 74 (12.16%)
         occurrences all number
    5
    10
    Gastric ulcer
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Gastritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    3 / 74 (4.05%)
         occurrences all number
    2
    3
    Gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    2 / 74 (2.70%)
         occurrences all number
    5
    2
    Gingival bleeding
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Abdominal pain upper
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences all number
    0
    3
    Haematemesis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Mouth ulceration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Nausea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    29 / 77 (37.66%)
    26 / 74 (35.14%)
         occurrences all number
    35
    29
    Odynophagia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    5 / 74 (6.76%)
         occurrences all number
    7
    6
    Oesophageal ulcer
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Oesophagitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    24 / 77 (31.17%)
    15 / 74 (20.27%)
         occurrences all number
    25
    15
    Proctalgia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Rectal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences all number
    0
    3
    Retching
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    9 / 74 (12.16%)
         occurrences all number
    3
    9
    Vomiting
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    9 / 74 (12.16%)
         occurrences all number
    7
    12
    Haematochezia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Bile duct stone
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Drug-induced liver injury
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hypertransaminasaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Immune-mediated hepatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 74 (2.70%)
         occurrences all number
    5
    2
    Dermatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Blister
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Alopecia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    6 / 74 (8.11%)
         occurrences all number
    7
    6
    Actinic keratosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Dry skin
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    2 / 74 (2.70%)
         occurrences all number
    2
    2
    Pruritus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    8 / 77 (10.39%)
    13 / 74 (17.57%)
         occurrences all number
    8
    18
    Pigmentation disorder
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Pemphigoid
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Neurodermatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Miliaria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Lichenoid keratosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Erythema multiforme
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Erythema
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    5 / 74 (6.76%)
         occurrences all number
    1
    7
    Eczema
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences all number
    0
    3
    Psoriasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    2
    Rash
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    19 / 74 (25.68%)
         occurrences all number
    7
    25
    Rash erythematous
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Skin toxicity
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Skin reaction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Rash maculo-papular
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    4 / 74 (5.41%)
         occurrences all number
    1
    4
    Rash macular
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    2
    1
    Pollakiuria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Renal failure
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Acute kidney injury
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Cystitis noninfective
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Dysuria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hypopituitarism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hypothyroidism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 77 (7.79%)
    2 / 74 (2.70%)
         occurrences all number
    6
    2
    Thyroiditis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hyperthyroidism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 77 (9.09%)
    4 / 74 (5.41%)
         occurrences all number
    7
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    7 / 74 (9.46%)
         occurrences all number
    3
    7
    Arthritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Myositis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Myalgia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    3 / 74 (4.05%)
         occurrences all number
    1
    3
    Musculoskeletal stiffness
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Musculoskeletal chest pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Intervertebral disc protrusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Haemarthrosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Flank pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Back pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    6 / 74 (8.11%)
         occurrences all number
    4
    6
    Neck pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Pain in extremity
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    3 / 74 (4.05%)
         occurrences all number
    0
    3
    Rotator cuff syndrome
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Osteoporosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Infections and infestations
    Bacteraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Molluscum contagiosum
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    COVID-19
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Cystitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Cytomegalovirus infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Device related infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Empyema
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Folliculitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    4
    Fungal skin infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Gastroenteritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Gingivitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Herpes zoster
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 74 (2.70%)
         occurrences all number
    0
    2
    Infectious pleural effusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Influenza
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Bronchitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Nasopharyngitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Tinea infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Oesophageal infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Onychomycosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Oral candidiasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Oral fungal infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Peri-implantitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Periodontitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Pharyngotonsillitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Pneumonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    8 / 74 (10.81%)
         occurrences all number
    3
    9
    Post-acute COVID-19 syndrome
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Pseudomembranous colitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    2 / 74 (2.70%)
         occurrences all number
    2
    2
    Sinusitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Oesophageal candidiasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    2
    Tooth abscess
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 74 (1.35%)
         occurrences all number
    1
    1
    Urinary tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    6 / 74 (8.11%)
         occurrences all number
    3
    10
    Vulvovaginal mycotic infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Tracheitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hyperglycaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    6 / 74 (8.11%)
         occurrences all number
    7
    7
    Hypocalcaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    4 / 74 (5.41%)
         occurrences all number
    3
    4
    Electrolyte imbalance
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Dehydration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    2 / 74 (2.70%)
         occurrences all number
    2
    2
    Decreased appetite
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    16 / 77 (20.78%)
    17 / 74 (22.97%)
         occurrences all number
    17
    20
    Cachexia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Hyperkalaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Hypermagnesaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Hypernatraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 74 (1.35%)
         occurrences all number
    7
    1
    Hyperuricaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    3 / 74 (4.05%)
         occurrences all number
    6
    4
    Hypoalbuminaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 77 (6.49%)
    10 / 74 (13.51%)
         occurrences all number
    6
    16
    Hypercholesterolaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    3
    0
    Malnutrition
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 74 (1.35%)
         occurrences all number
    0
    1
    Iron deficiency
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hypoproteinaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 74 (0.00%)
         occurrences all number
    2
    0
    Hypophosphataemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 77 (0.00%)
    5 / 74 (6.76%)
         occurrences all number
    0
    5
    Hypophagia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 74 (0.00%)
         occurrences all number
    1
    0
    Hyponatraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    9 / 77 (11.69%)
    6 / 74 (8.11%)
         occurrences all number
    15
    13
    Hypomagnesaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 74 (5.41%)
         occurrences all number
    3
    5
    Hypokalaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 74 (5.41%)
         occurrences all number
    3
    4
    Hypochloraemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 74 (1.35%)
         occurrences all number
    6
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Mar 2019
    • To include Programmed death-ligand 1 (PD-L1) expression in tumor cells as stratification factor in the expansion part of the study. • To include information regarding PD-L1 tumor expression and clarify inclusion criteria. • To add details on planned tests for overall survival analyses.
    05 Jul 2019
    • To provide detailed information regarding the Independent Data Monitoring Committee (IDMC) safety reviews. • To add evaluation of a potential biomarker. • To clarify that bone palliative radiotherapy `is allowed during the study. • To exclude participants with history of bleeding diatheses or recent major bleeding events. • To specify the sequence of treatment administration when the radiotherapy is delivered at a separate location.
    22 Jun 2021
    • To reduce the sample size from 350 subjects to approximately 160 subjects to provide an earlier result from the primary analysis to give insight into the potential benefit of M7824 in subjects with unresectable Stage III NSCLC. • To update the risk classification and minimization measures.

    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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