Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multicenter, Randomized, Open-label Study in Patients with esophageal Cancer refractory or intolerant to Combination Therapy with Fluoropyrimidine and Platinum-based Drugs

    Summary
    EudraCT number
    		 2015-003339-36
    Trial protocol
    		 DE   DK   GB   IT  
    Global end of trial date
    23 Oct 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Dec 2024
    First version publication date
    06 Dec 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-473
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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
    23 Oct 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Oct 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare overall survival (OS) between the nivolumab group and control group (docetaxel or paclitaxel) in patients with esophageal cancer refractory or intolerant to combination therapy with fluoropyrimidine- and platinum-based drugs.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Dec 2015
    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
    Japan: 274
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 59
    Country: Number of subjects enrolled
    Taiwan: 68
    Country: Number of subjects enrolled
    United States: 1
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Denmark: 4
    Worldwide total number of subjects
    419
    EEA total number of subjects
    17
    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)
    197
    From 65 to 84 years
    221
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 419 participants were randomized, 417 were treated

    Period 1
    Period 1 title
    Pre-Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab Arm
    Arm description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg at 2-week intervals

    Arm title
    		 Active Comparator Arm （Docetaxel/Paclitaxel）
    Arm description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg/m2 weekly for 6 weeks in succession followed by a 2-week drug holiday

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m2 at 3-week intervals

    Number of subjects in period 1
    		Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Started
    210
    209
    Completed
    209
    208
    Not completed
    1
    1
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    -
    1
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nivolumab Arm
    Arm description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg at 2-week intervals

    Arm title
    		 Active Comparator Arm （Docetaxel/Paclitaxel）
    Arm description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg/m2 weekly for 6 weeks in succession followed by a 2-week drug holiday

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m2 at 3-week intervals

    Number of subjects in period 2
    		Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Started
    209
    208
    Completed
    0
    0
    Not completed
    209
    208
         Other reasons
    209
    208

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Nivolumab Arm
    Reporting group description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

    Reporting group title
    Active Comparator Arm （Docetaxel/Paclitaxel）
    Reporting group description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

    Reporting group values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel） Total
    Number of subjects
    		 210 209 419
    Age Categorical
    Units: participants
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 112 85 197
        >=65 years
    		 98 124 222
    Age Continuous
    Units: years
        arithmetic mean (inter-quartile range (Q1-Q3))
    		 64 (57 to 69) 67 (57 to 72) -
    Sex: Female, Male
    Units: participants
        Female
    		 31 24 55
        Male
    		 179 185 364
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 201 200 401
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 9 9 18
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Nivolumab Arm
    Reporting group description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

    Reporting group title
    Active Comparator Arm （Docetaxel/Paclitaxel）
    Reporting group description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Reporting group title
    Nivolumab Arm
    Reporting group description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

    Reporting group title
    Active Comparator Arm （Docetaxel/Paclitaxel）
    Reporting group description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

    Primary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival (OS) is defined as the time from randomization to death from any cause. For participants lost to follow-up and participants who were alive at the time of data cutoff date, data was censored at the time the participant was last confirmed to be alive. Conducted using the Kaplan-Meier method.
    End point type
    Primary
    End point timeframe
    From date of randomization until the date of death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Months
        median (confidence interval 95%)
    10.91 (9.23 to 13.34)
    8.51 (7.29 to 9.86)
    Statistical analysis title
    		 Hazard Ratio
    Comparison groups
    Nivolumab Arm v Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0189
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.97

    Secondary: Progression-Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS)
    End point description
    Progression-free survival (PFS) is the time from randomization until disease progression or worsening. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Conducted by using the Kaplan-Meier method
    End point type
    Secondary
    End point timeframe
    From date of randomization until progressive disease or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Months
        median (confidence interval 95%)
    1.68 (1.51 to 2.73)
    3.35 (2.99 to 4.21)
    Statistical analysis title
    		 Hazard Ratio (HR)
    Comparison groups
    Nivolumab Arm v Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.33

    Secondary: Duration of Response (DoR)

    		 Close Top of page
    End point title
    		 Duration of Response (DoR)
    End point description
    Duration of response (DoR) measures the length of time that a tumor responds to treatment without growing or spreading i.e. the length of time a participant had either a complete response (CR) or partial response (PR) to study treatment. Complete Response (CR): Disappearance of all (non-lymph node) target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Conducted by using the Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    From randomization until progression or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    171
    158
    Units: Months
        median (confidence interval 95%)
    6.93 (5.39 to 11.14)
    3.91 (2.79 to 4.17)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR)
    End point description
    Objective response rate (ORR) is defined as the percentage of participants whose best overall response is assessed as either complete response (CR) or partial response (PR). Overall response and best overall response was determined solely by imaging assessment according to the RECIST Guideline Version 1.1 and did not take into account any clinical/symptomatic progression. Complete Response (CR): Disappearance of all (non-lymph node) target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From randomization until progressive disease or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Percent of Participants
        number (confidence interval 95%)
    15.7 (11.1 to 21.4)
    16.3 (11.5 to 22.0)
    Statistical analysis title
    		 Odds Ratio (OR)
    Comparison groups
    Nivolumab Arm v Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.62

    Secondary: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR)
    End point description
    Disease control rate is defined as the percentage of participants whose best overall response is assessed as complete response (CR), partial response (PR) or stable disease (SD). Complete Response (CR): Disappearance of all (non-lymph node) target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameter while on study.
    End point type
    Secondary
    End point timeframe
    From randomization until progressive disease or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Percent of participants
        number (confidence interval 95%)
    30.5 (24.3 to 37.2)
    47.4 (40.4 to 54.4)
    Statistical analysis title
    		 Odds Ratio (OR)
    Comparison groups
    Nivolumab Arm v Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 0.72

    Secondary: Time to Response (TTR)

    		 Close Top of page
    End point title
    		 Time to Response (TTR)
    End point description
    Time to response (TTR) is the duration from the start of treatment to the first observation of a predefined clinical response. Complete Response (CR): Disappearance of all (non-lymph node) target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From randomization until complete response or partial response (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Months
        arithmetic mean (full range (min-max))
    2.66 (1.2 to 22.3)
    1.48 (1.2 to 5.6)
    No statistical analyses for this end point

    Secondary: Best Overall Response (BOR)

    		 Close Top of page
    End point title
    		 Best Overall Response (BOR)
    End point description
    Best overall response (BOR) refers to the best response recorded from the start of the treatment until disease progression or recurrence. Complete Response (CR): Disappearance of all (non-lymph node) target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Secondary
    End point timeframe
    From randomization until progressive disease or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Percent of participants
    number (not applicable)
        Complete Response (CR)
    1.0
    1.0
        Partial Response (PR)
    14.8
    15.3
        Progressive Disease (PD)
    44.3
    24.4
        Stable Disease (SD)
    14.8
    31.1
        Not Evaluable (NE)
    25.2
    28.2
    No statistical analyses for this end point

    Secondary: Best Percent Reduction from Baseline in the Sum of Diameters of the Target Lesion

    		 Close Top of page
    End point title
    		 Best Percent Reduction from Baseline in the Sum of Diameters of the Target Lesion
    End point description
    Best percent reduction from baseline in the sum of diameters of the target lesion was used to evaluate the effectiveness of treatment in reducing tumor size. The diameter data excludes that obtained after an overall response of progressive disease (PD) and after new treatment for cancer.
    End point type
    Secondary
    End point timeframe
    From randomization until progressive disease or death due to any cause (assessed up to approximately 58 months)
    End point values
    		 Nivolumab Arm Active Comparator Arm （Docetaxel/Paclitaxel）
    Number of subjects analysed
    210
    209
    Units: Percent reduction from baseline
    100
    100
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Monitoring for non-serious adverse events (AEs) continued until 28 days after the treatment phase ended. Serious AEs were tracked during the treatment period and for 100 days after the last dose.
    Adverse event reporting additional description
    Serious AEs and non-serious AEs included participants who received at least one dose of study medicine.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Active Comparator Arm （Docetaxel/Paclitaxel）
    Reporting group description
    		 Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

    Reporting group title
    Nivolumab Arm
    Reporting group description
    		 Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

    Serious adverse events
    		 Active Comparator Arm （Docetaxel/Paclitaxel） Nivolumab Arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    78 / 208 (37.50%)
    70 / 209 (33.49%)
         number of deaths (all causes)
    186
    178
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cancer pain
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tumour haemorrhage
         subjects affected / exposed
    1 / 208 (0.48%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin cancer
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Jejunostomy
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         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
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 208 (0.48%)
    6 / 209 (2.87%)
         occurrences causally related to treatment / all
    0 / 1
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Disease progression
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Stenosis
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 208 (1.44%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    3 / 208 (1.44%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    Pneumonia aspiration
         subjects affected / exposed
    2 / 208 (0.96%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 208 (1.44%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    3 / 208 (1.44%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    3 / 3
    4 / 4
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Dyspnoea
         subjects affected / exposed
    1 / 208 (0.48%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheal fistula
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagobronchial fistula
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    3 / 208 (1.44%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radiation pneumonitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma site extravasation
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Tracheo-oesophageal fistula
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Pericarditis
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         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
    Bone marrow failure
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    16 / 208 (7.69%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    23 / 23
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 208 (0.96%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    2 / 208 (0.96%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ileus
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 208 (0.96%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 208 (0.96%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 208 (0.96%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric fistula
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aorto-oesophageal fistula
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct obstruction
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Excessive granulation tissue
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenocorticotropic hormone deficiency
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         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
    Fistula
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 208 (0.96%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    13 / 208 (6.25%)
    10 / 209 (4.78%)
         occurrences causally related to treatment / all
    3 / 13
    2 / 11
         deaths causally related to treatment / all
    1 / 2
    0 / 2
    Postoperative wound infection
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 208 (0.96%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle abscess
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    5 / 208 (2.40%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord abscess
         subjects affected / exposed
    1 / 208 (0.48%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    2 / 208 (0.96%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 208 (0.48%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 208 (0.48%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 208 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 208 (0.48%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    6 / 208 (2.88%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    7 / 7
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 208 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Active Comparator Arm （Docetaxel/Paclitaxel） Nivolumab Arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    203 / 208 (97.60%)
    165 / 209 (78.95%)
    Investigations
    Weight decreased
         subjects affected / exposed
    11 / 208 (5.29%)
    11 / 209 (5.26%)
         occurrences all number
    11
    11
    Neutrophil count decreased
         subjects affected / exposed
    76 / 208 (36.54%)
    4 / 209 (1.91%)
         occurrences all number
    185
    12
    Lymphocyte count decreased
         subjects affected / exposed
    21 / 208 (10.10%)
    5 / 209 (2.39%)
         occurrences all number
    39
    19
    Aspartate aminotransferase increased
         subjects affected / exposed
    7 / 208 (3.37%)
    14 / 209 (6.70%)
         occurrences all number
    8
    14
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 208 (3.37%)
    11 / 209 (5.26%)
         occurrences all number
    9
    11
    White blood cell count decreased
         subjects affected / exposed
    72 / 208 (34.62%)
    2 / 209 (0.96%)
         occurrences all number
    173
    2
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    23 / 208 (11.06%)
    0 / 209 (0.00%)
         occurrences all number
    23
    0
    Dysgeusia
         subjects affected / exposed
    14 / 208 (6.73%)
    5 / 209 (2.39%)
         occurrences all number
    14
    5
    Peripheral sensory neuropathy
         subjects affected / exposed
    48 / 208 (23.08%)
    1 / 209 (0.48%)
         occurrences all number
    50
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    61 / 208 (29.33%)
    25 / 209 (11.96%)
         occurrences all number
    76
    28
    Leukopenia
         subjects affected / exposed
    18 / 208 (8.65%)
    0 / 209 (0.00%)
         occurrences all number
    61
    0
    Neutropenia
         subjects affected / exposed
    40 / 208 (19.23%)
    1 / 209 (0.48%)
         occurrences all number
    94
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    39 / 208 (18.75%)
    29 / 209 (13.88%)
         occurrences all number
    51
    40
    Malaise
         subjects affected / exposed
    50 / 208 (24.04%)
    13 / 209 (6.22%)
         occurrences all number
    72
    16
    Fatigue
         subjects affected / exposed
    52 / 208 (25.00%)
    20 / 209 (9.57%)
         occurrences all number
    54
    21
    Chest pain
         subjects affected / exposed
    4 / 208 (1.92%)
    13 / 209 (6.22%)
         occurrences all number
    5
    15
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    17 / 208 (8.17%)
    14 / 209 (6.70%)
         occurrences all number
    17
    15
    Stomatitis
         subjects affected / exposed
    26 / 208 (12.50%)
    7 / 209 (3.35%)
         occurrences all number
    28
    7
    Abdominal pain
         subjects affected / exposed
    8 / 208 (3.85%)
    13 / 209 (6.22%)
         occurrences all number
    9
    15
    Constipation
         subjects affected / exposed
    40 / 208 (19.23%)
    36 / 209 (17.22%)
         occurrences all number
    42
    36
    Diarrhoea
         subjects affected / exposed
    34 / 208 (16.35%)
    39 / 209 (18.66%)
         occurrences all number
    36
    42
    Dysphagia
         subjects affected / exposed
    3 / 208 (1.44%)
    13 / 209 (6.22%)
         occurrences all number
    3
    13
    Nausea
         subjects affected / exposed
    40 / 208 (19.23%)
    23 / 209 (11.00%)
         occurrences all number
    41
    26
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    8 / 208 (3.85%)
    13 / 209 (6.22%)
         occurrences all number
    12
    13
    Cough
         subjects affected / exposed
    25 / 208 (12.02%)
    33 / 209 (15.79%)
         occurrences all number
    27
    35
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    7 / 208 (3.37%)
    12 / 209 (5.74%)
         occurrences all number
    8
    12
    Pruritus
         subjects affected / exposed
    15 / 208 (7.21%)
    26 / 209 (12.44%)
         occurrences all number
    18
    29
    Alopecia
         subjects affected / exposed
    100 / 208 (48.08%)
    3 / 209 (1.44%)
         occurrences all number
    100
    3
    Rash
         subjects affected / exposed
    40 / 208 (19.23%)
    26 / 209 (12.44%)
         occurrences all number
    43
    28
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    13 / 208 (6.25%)
    12 / 209 (5.74%)
         occurrences all number
    14
    12
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    3 / 208 (1.44%)
    21 / 209 (10.05%)
         occurrences all number
    3
    21
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    22 / 208 (10.58%)
    6 / 209 (2.87%)
         occurrences all number
    23
    6
    Arthralgia
         subjects affected / exposed
    25 / 208 (12.02%)
    10 / 209 (4.78%)
         occurrences all number
    29
    12
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 208 (6.25%)
    15 / 209 (7.18%)
         occurrences all number
    17
    34
    Nasopharyngitis
         subjects affected / exposed
    10 / 208 (4.81%)
    13 / 209 (6.22%)
         occurrences all number
    15
    18
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    68 / 208 (32.69%)
    40 / 209 (19.14%)
         occurrences all number
    79
    42

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 May 2019
    To include the timing of informed consent from subjects to enter the CA209-473 Extension phase and to set wash-out period before the first CA209-473 dose in the CA209-473 Extension phase.

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

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

    European Medicines Agency © 1995-Fri May 02 08:01:06 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA