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    Clinical Trial Results:
    A Phase 3 Randomized Study of Lenvatinib in Combination with Pembrolizumab Versus Standard of Care in Participants with Metastatic Colorectal Cancer Who Have Received and Progressed On or After or Became Intolerant to Prior Treatment

    Summary
    EudraCT number
    		 2020-004289-20
    Trial protocol
    		 DE   DK  
    Global end of trial date
    27 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    7902-017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04776148
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Protocol Number: MK-7902-017, Merck: LEAP-017, Eisai Protocol Number: E7080-G000-325, jRCT: 2031200453
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.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
    27 Sep 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Sep 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Sep 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to assess the safety and efficacy of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in participants with metastatic colorectal cancer. The study will also compare lenvatinib plus pembrolizumab with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil hydrochloride). The primary study hypothesis is that lenvatinib plus pembrolizumab is superior to standard of care with respect to overall survival. The Global portion, or Global Cohort, will include all participants who are enrolled during the Global enrollment period and will be the primary analysis population for the study. The China Cohort will include both participants enrolled in China for the Global Cohort plus those participants enrolled in China as part of the China extension enrollment period.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Mar 2021
    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: 21
    Country: Number of subjects enrolled
    Australia: 24
    Country: Number of subjects enrolled
    Canada: 25
    Country: Number of subjects enrolled
    China: 100
    Country: Number of subjects enrolled
    Denmark: 25
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Israel: 36
    Country: Number of subjects enrolled
    Japan: 63
    Country: Number of subjects enrolled
    Korea, Republic of: 41
    Country: Number of subjects enrolled
    Russian Federation: 22
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    Taiwan: 33
    Country: Number of subjects enrolled
    Türkiye: 50
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    563
    EEA total number of subjects
    91
    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)
    395
    From 65 to 84 years
    167
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 480 participants were enrolled in the Global Cohort, including 17 participants from China. An additional 83 participants were subsequently enrolled in the China extension, bringing the total number of participants in the China Cohort to 100 and the overall study population to 563.

    Pre-assignment
    Screening details
    		 The protocol specified non-alpha controlled final analyses for the China Cohort was conducted with a 27-Sep 2024 data cutoff, after the protocol-specified final analyses of the Global Cohort was completed on 20-Feb-2023.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lenvatinib+pembrolizumab
    Arm description
    		 Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
    Arm type
    		 Experimental

    Investigational medicinal product name
    lenvatinib
    Investigational medicinal product code
    Other name
    MK-7902 E7080
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    oral capsule

    Investigational medicinal product name
    pembrolizumab
    Investigational medicinal product code
    Other name
    KEYTRUDA® MK-3475
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion

    Arm title
    		 Standard of Care (SOC) treatment
    Arm description
    		 Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    TAS-102 (trifluridine andtipiracil)
    Investigational medicinal product code
    Other name
    LONSURF®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    oral tablet

    Investigational medicinal product name
    regorafenib
    Investigational medicinal product code
    Other name
    STIVARGA® REGONIX®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    oral tablet

    Number of subjects in period 1
    		Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Started
    282
    281
    Treated
    279
    277
    Global Cohort Efficacy
    241
    239
    China Cohort Efficacy
    53
    47
    Global Cohort Safety
    238
    235
    China Cohort Safety
    53
    47
    Completed
    0
    0
    Not completed
    282
    281
         Adverse event, serious fatal
    249
    260
         Consent withdrawn by subject
    3
    4
         Withdrawal by Parent/Guardian
    -
    1
         Sponsor Decision
    30
    15
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lenvatinib+pembrolizumab
    Reporting group description
    		 Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

    Reporting group title
    Standard of Care (SOC) treatment
    Reporting group description
    		 Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.

    Reporting group values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment Total
    Number of subjects
    		 282 281 563
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 199 196 395
        From 65-84 years
    		 82 85 167
        85 years and over
    		 1 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 57.1 ( 11.7 ) 57.2 ( 11.7 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 121 116 237
        Male
    		 161 165 326
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 122 123 245
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 5 3 8
        White
    		 152 152 304
        More than one race
    		 1 1 2
        Unknown or Not Reported
    		 2 2 4
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 26 13 39
        Not Hispanic or Latino
    		 255 267 522
        Unknown or Not Reported
    		 1 1 2
    Presence of Liver Metastasis
    Number of participants with liver metastasis at baseline (Yes/No)
    Units: Subjects
        Yes
    		 192 190 382
        No metastasis at baseline
    		 90 91 181

    End points

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    End points reporting groups
    Reporting group title
    Lenvatinib+pembrolizumab
    Reporting group description
    		 Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

    Reporting group title
    Standard of Care (SOC) treatment
    Reporting group description
    		 Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.

    Primary: Global Cohort: Overall Survival (OS)

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    End point title
    		 Global Cohort: Overall Survival (OS)
    End point description
    OS was defined as the time from randomization to the date of death from any cause. OS is presented for all randomized participants in the Global Cohort. Per the supplemental Statistical Analysis Plan (sSAP), Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Primary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    241
    239
    Units: Months
        median (confidence interval 95%)
    9.8 (8.4 to 11.6)
    9.3 (8.2 to 10.9)
    Statistical analysis title
    		 Global OS comparison
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate stratified by presence of liver metastasis (Yes/No).
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0379 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.02
    Notes
    [1] - One-sided p-value based on log-rank test stratified by presence of liver metastasis.

    Primary: China Cohort: Overall Survival (OS)

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    End point title
    		 China Cohort: Overall Survival (OS)
    End point description
    OS was defined as the time from randomization to the date of death from any cause. OS is presented for all randomized participants in the China Cohort. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.
    End point type
    Primary
    End point timeframe
    Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    53
    47
    Units: Months
        median (confidence interval 95%)
    10.9 (8.8 to 16.5)
    10.2 (6.1 to 12.7)
    Statistical analysis title
    		 China OS comparison
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3574 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.42
    Notes
    [2] - One-sided p-value based on log-rank test.

    Secondary: Global Cohort: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

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    End point title
    		 Global Cohort: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    End point description
    PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per modified RECIST 1.1 is presented for all randomized participants in the Global Cohort. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Secondary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    241
    239
    Units: Months
        median (confidence interval 95%)
    3.8 (3.7 to 5.1)
    3.3 (2.0 to 3.7)
    Statistical analysis title
    		 Global PFS comparison
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate stratified by presence of liver metastasis (Yes/No).
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003 [3]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 0.85
    Notes
    [3] - One-sided p-value based on log-rank test stratified by presence of liver metastasis.

    Secondary: China Cohort: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

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    End point title
    		 China Cohort: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    End point description
    PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per modified RECIST 1.1 is presented for all randomized participants in the China Cohort. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.
    End point type
    Secondary
    End point timeframe
    Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    53
    47
    Units: Months
        median (confidence interval 95%)
    3.7 (2.9 to 3.9)
    2.4 (1.9 to 5.4)
    Statistical analysis title
    		 China PFS comparison
    Statistical analysis description
    Based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7421 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.15
    Confidence interval
         level
    		 85%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.77
    Notes
    [4] - One-sided p-value based on log-rank test.

    Secondary: Global Cohort: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR

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    End point title
    		 Global Cohort: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
    End point description
    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR per modified RECIST 1.1 assessed by BICR is presented for all randomized participants in the Global Cohort. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Secondary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    241
    239
    Units: Percentage of Participants
        number (confidence interval 95%)
    10.4 (6.8 to 14.9)
    1.7 (0.5 to 4.2)
    Statistical analysis title
    		 Global ORR comparison
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Chi-squared
    Parameter type
    		 Difference in Percentage vs. SOC
    Point estimate
    8.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.7
         upper limit
    		 13.5

    Secondary: China Cohort: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR

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    End point title
    		 China Cohort: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
    End point description
    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR per modified RECIST 1.1 assessed by BICR is presented for all randomized participants in the Global Cohort. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.
    End point type
    Secondary
    End point timeframe
    Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    53
    47
    Units: Percentage of Participants
        number (confidence interval 95%)
    7.5 (2.1 to 18.2)
    4.3 (0.5 to 14.5)
    Statistical analysis title
    		 China ORR comparison
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2456
    Method
    		 Chi-squared
    Parameter type
    		 Difference in Percentage vs. SOC
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 14.3

    Secondary: Global Cohort: Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR

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    End point title
    		 Global Cohort: Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
    End point description
    For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause. DOR as assessed by BICR per modified RECIST 1.1 is presented for all randomized participants in the Global Cohort. Values of 9999 indicate that the upper limit was not reached at time of data cut-off due to insufficient number of responding participants with relapse. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Secondary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    25
    4
    Units: Months
        median (confidence interval 95%)
    11.1 (7.7 to 9999)
    7.6 (6.0 to 9999)
    No statistical analyses for this end point

    Secondary: China Cohort: Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR

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    End point title
    		 China Cohort: Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
    End point description
    For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause. DOR as assessed by BICR per modified RECIST 1.1 is presented for all randomized participants in the China Cohort. Values of 8888 indicate that the upper limit was not reached at time of data cut-off due to insufficient number of responding participants with relapse. A value of 9999 indicates that the median duration and upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort.
    End point type
    Secondary
    End point timeframe
    Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    4
    2
    Units: Months
        median (confidence interval 95%)
    4.4 (3.5 to 8888)
    9999 (9.1 to 9999)
    No statistical analyses for this end point

    Secondary: Global Cohort: Number of Participants Who Experience an Adverse Event (AE)

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    End point title
    		 Global Cohort: Number of Participants Who Experience an Adverse Event (AE)
    End point description
    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. All randomized participants in the Global Cohort who received at least one dose of study treatment were analyzed. Two participants randomized to pembrolizumab plus lenvatinib group were incorrectly treated with SOC; these participants were included in the SOC group for safety analyses. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Secondary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    238
    235
    Units: Participants
    237
    230
    No statistical analyses for this end point

    Secondary: China Cohort: Number of Participants Who Experience an Adverse Event (AE)

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    End point title
    		 China Cohort: Number of Participants Who Experience an Adverse Event (AE)
    End point description
    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. All randomized participants in the China Cohort who received at least one dose of study treatment were analyzed. Per the sSAP, the China Cohort was evaluated for safety separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.
    End point type
    Secondary
    End point timeframe
    Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    53
    47
    Units: Participants
    53
    47
    No statistical analyses for this end point

    Secondary: Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

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    End point title
    		 Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
    End point description
    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued any study treatment due to an adverse event is presented. All randomized participants in the Global Cohort who received at least one dose of study treatment were analyzed. Two participants randomized to pembrolizumab plus lenvatinib group were incorrectly treated with SOC; these participants were included in the SOC group for safety analyses. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.
    End point type
    Secondary
    End point timeframe
    Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    238
    235
    Units: Participants
    37
    10
    No statistical analyses for this end point

    Secondary: China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

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    End point title
    		 China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
    End point description
    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued any study treatment due to an adverse event is reported. All randomized participants in the China Cohort who received at least one dose of study treatment were analyzed. Per the sSAP, the China Cohort was evaluated for safety separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    53
    47
    Units: Participants
    8
    5
    No statistical analyses for this end point

    Secondary: Global Cohort: Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

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    End point title
    		 Global Cohort: Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
    End point description
    The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this Patient Reported Outcome (PRO) was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and 8 weeks
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    234
    229
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -4.91 (-7.67 to -2.14)
    -7.62 (-10.48 to -4.76)
    Statistical analysis title
    		 Difference in LS means at Week 8 (Items 29 & 30)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    463
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1553 [5]
    Method
    		 cLDA model
    Parameter type
    		 Difference in least squares means
    Point estimate
    2.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.03
         upper limit
    		 6.46
    Notes
    [5] - Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

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    End point title
    		 Global Cohort: Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
    End point description
    The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function. The change from baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) scale score is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and 8 weeks
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    234
    229
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -6.16 (-8.51 to -3.82)
    -7.32 (-9.75 to -4.90)
    Statistical analysis title
    		 Difference in LS means at Week 8 (Items 1-5)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    463
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4967 [6]
    Method
    		 cLDA model
    Parameter type
    		 Difference in LS means
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.19
         upper limit
    		 4.51
    Notes
    [6] - Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

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    End point title
    		 Global Cohort: Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score
    End point description
    The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question "Have you lacked appetite?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and 8 weeks
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    234
    230
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    12.44 (8.50 to 16.38)
    9.08 (5.00 to 13.15)
    Statistical analysis title
    		 Difference in LS means at Week 8 (Item 13)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2271 [7]
    Method
    		 cLDA model
    Parameter type
    		 Difference in LS means
    Point estimate
    3.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 8.82
    Notes
    [7] - Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

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    End point title
    		 Global Cohort: Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
    End point description
    The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question "Did you have a bloated feeling in your abdomen?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-CR29 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and 8 weeks
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    234
    230
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -0.30 (-3.78 to 3.19)
    5.16 (1.56 to 8.77)
    Statistical analysis title
    		 Difference in LS means at Week 8 (Item 37)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0264 [8]
    Method
    		 cLDA model
    Parameter type
    		 Difference in LS means
    Point estimate
    -5.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.27
         upper limit
    		 -0.65
    Notes
    [8] - Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

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    End point title
    		 Global Cohort: Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
    End point description
    TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to approximately 21 months
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    227
    220
    Units: Months
        median (confidence interval 95%)
    1.4 (1.1 to 1.9)
    1.4 (1.0 to 1.8)
    Statistical analysis title
    		 TTD (Item 29 & Item 30)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    447
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4338 [9]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.14
    Notes
    [9] - Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

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    End point title
    		 Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
    End point description
    TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to approximately 21 months
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    226
    221
    Units: Months
        median (confidence interval 95%)
    1.8 (1.4 to 2.0)
    2.0 (1.4 to 2.3)
    Statistical analysis title
    		 TTD (Items 1-5)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    447
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4316 [10]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.38
    Notes
    [10] - Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score

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    End point title
    		 Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
    End point description
    TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in appetite loss (QLQ-C30 Item 13) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD, as assessed based on a ≥10-point change (increase) from baseline in appetite loss score, is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to approximately 21 months
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    226
    221
    Units: Months
        median (confidence interval 95%)
    1.4 (1.1 to 1.8)
    1.4 (1.1 to 1.9)
    Statistical analysis title
    		 TTD (Item 13)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    447
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5587 [11]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.32
    Notes
    [11] - Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).

    Secondary: Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

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    End point title
    		 Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
    End point description
    TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in bloating (QLQ-CR29 Item 37) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD, as assessed based on a ≥10-point change (increase) from baseline in bloating score, is presented for all participants in the Global Cohort who have at least one assessment available for EORTC QLQ-CR29 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to approximately 21 months
    End point values
    		 Lenvatinib+pembrolizumab Standard of Care (SOC) treatment
    Number of subjects analysed
    224
    221
    Units: Months
        median (confidence interval 95%)
    3.4 (2.3 to 5.2)
    3.2 (2.3 to 5.6)
    Statistical analysis title
    		 TTD (Item 37)
    Comparison groups
    Lenvatinib+pembrolizumab v Standard of Care (SOC) treatment
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6794 [12]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.23
    Notes
    [12] - Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 41 months (through End of Trial database cut-off date of 27-Sep-2024). 2 participants randomized to lenvatinib plus pembrolizumab were incorrectly treated with SOC and were included in SOC arm.
    Adverse event reporting additional description
    All-cause deaths reported for all randomized participants (N=563). Serious and nonserious AEs include all treated participants according to treatment received. MedDRA V27.0 terms 'Neoplasm progression' 'Malignant neoplasm progression' and 'Disease progression' unrelated to the drug are excluded.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Standard Of Care Treatment
    Reporting group description
    		 Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.

    Reporting group title
    Lenvatinib + Pembrolizumab
    Reporting group description
    		 Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.

    Serious adverse events
    		 Standard Of Care Treatment Lenvatinib + Pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    66 / 277 (23.83%)
    117 / 279 (41.94%)
         number of deaths (all causes)
    264
    251
         number of deaths resulting from adverse events
    4
    5
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Sinonasal papilloma
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 277 (0.00%)
    6 / 279 (2.15%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Generalised oedema
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 277 (1.44%)
    4 / 279 (1.43%)
         occurrences causally related to treatment / all
    1 / 4
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Female genital tract fistula
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fluid collection
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 277 (0.00%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pneumothorax
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 277 (0.00%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Granulocyte count decreased
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium test positive
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrointestinal anastomotic leak
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma prolapse
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrioventricular block complete
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery stenosis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Brain stem infarction
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    3 / 277 (1.08%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 277 (2.17%)
    5 / 279 (1.79%)
         occurrences causally related to treatment / all
    1 / 6
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal inflammation
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 277 (1.08%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 277 (1.08%)
    4 / 279 (1.43%)
         occurrences causally related to treatment / all
    4 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flatulence
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal perforation
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    3 / 277 (1.08%)
    5 / 279 (1.79%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated enterocolitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated pancreatitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal fistula
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 277 (0.36%)
    4 / 279 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal ulcer
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal haemorrhage
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal ulcer
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal perforation
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 277 (0.00%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 277 (1.08%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder obstruction
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant biliary obstruction
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 277 (0.36%)
    4 / 279 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated nephritis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         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
    Pathological fracture
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal wall abscess
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 277 (0.36%)
    4 / 279 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 277 (1.08%)
    5 / 279 (1.79%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 277 (0.72%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin infection
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         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
    4 / 277 (1.44%)
    6 / 279 (2.15%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 279 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperammonaemia
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 279 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 279 (1.08%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 279 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Standard Of Care Treatment Lenvatinib + Pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    263 / 277 (94.95%)
    273 / 279 (97.85%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    63 / 277 (22.74%)
    156 / 279 (55.91%)
         occurrences all number
    81
    221
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    16 / 277 (5.78%)
    14 / 279 (5.02%)
         occurrences all number
    18
    15
    Fatigue
         subjects affected / exposed
    67 / 277 (24.19%)
    78 / 279 (27.96%)
         occurrences all number
    81
    88
    Asthenia
         subjects affected / exposed
    36 / 277 (13.00%)
    49 / 279 (17.56%)
         occurrences all number
    45
    62
    Mucosal inflammation
         subjects affected / exposed
    8 / 277 (2.89%)
    18 / 279 (6.45%)
         occurrences all number
    8
    20
    Pyrexia
         subjects affected / exposed
    24 / 277 (8.66%)
    40 / 279 (14.34%)
         occurrences all number
    32
    50
    Oedema peripheral
         subjects affected / exposed
    8 / 277 (2.89%)
    26 / 279 (9.32%)
         occurrences all number
    8
    26
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    24 / 277 (8.66%)
    29 / 279 (10.39%)
         occurrences all number
    27
    39
    Dysphonia
         subjects affected / exposed
    21 / 277 (7.58%)
    57 / 279 (20.43%)
         occurrences all number
    24
    62
    Dyspnoea
         subjects affected / exposed
    21 / 277 (7.58%)
    16 / 279 (5.73%)
         occurrences all number
    24
    18
    Epistaxis
         subjects affected / exposed
    2 / 277 (0.72%)
    14 / 279 (5.02%)
         occurrences all number
    2
    16
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    20 / 277 (7.22%)
    19 / 279 (6.81%)
         occurrences all number
    20
    21
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    17 / 277 (6.14%)
    27 / 279 (9.68%)
         occurrences all number
    17
    33
    Aspartate aminotransferase increased
         subjects affected / exposed
    39 / 277 (14.08%)
    67 / 279 (24.01%)
         occurrences all number
    49
    90
    Amylase increased
         subjects affected / exposed
    5 / 277 (1.81%)
    16 / 279 (5.73%)
         occurrences all number
    7
    17
    Alanine aminotransferase increased
         subjects affected / exposed
    30 / 277 (10.83%)
    50 / 279 (17.92%)
         occurrences all number
    38
    68
    Blood bilirubin increased
         subjects affected / exposed
    41 / 277 (14.80%)
    46 / 279 (16.49%)
         occurrences all number
    52
    60
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    2 / 277 (0.72%)
    37 / 279 (13.26%)
         occurrences all number
    2
    57
    Blood creatinine increased
         subjects affected / exposed
    8 / 277 (2.89%)
    21 / 279 (7.53%)
         occurrences all number
    11
    30
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    9 / 277 (3.25%)
    14 / 279 (5.02%)
         occurrences all number
    9
    15
    Neutrophil count decreased
         subjects affected / exposed
    48 / 277 (17.33%)
    14 / 279 (5.02%)
         occurrences all number
    151
    34
    Platelet count decreased
         subjects affected / exposed
    32 / 277 (11.55%)
    60 / 279 (21.51%)
         occurrences all number
    59
    91
    Weight decreased
         subjects affected / exposed
    26 / 277 (9.39%)
    65 / 279 (23.30%)
         occurrences all number
    27
    69
    White blood cell count decreased
         subjects affected / exposed
    36 / 277 (13.00%)
    15 / 279 (5.38%)
         occurrences all number
    118
    20
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    21 / 277 (7.58%)
    19 / 279 (6.81%)
         occurrences all number
    24
    19
    Headache
         subjects affected / exposed
    14 / 277 (5.05%)
    45 / 279 (16.13%)
         occurrences all number
    17
    61
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    60 / 277 (21.66%)
    49 / 279 (17.56%)
         occurrences all number
    73
    64
    Neutropenia
         subjects affected / exposed
    33 / 277 (11.91%)
    8 / 279 (2.87%)
         occurrences all number
    82
    22
    Thrombocytopenia
         subjects affected / exposed
    12 / 277 (4.33%)
    17 / 279 (6.09%)
         occurrences all number
    18
    25
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    16 / 277 (5.78%)
    27 / 279 (9.68%)
         occurrences all number
    20
    29
    Abdominal pain
         subjects affected / exposed
    45 / 277 (16.25%)
    58 / 279 (20.79%)
         occurrences all number
    56
    69
    Constipation
         subjects affected / exposed
    44 / 277 (15.88%)
    43 / 279 (15.41%)
         occurrences all number
    58
    51
    Abdominal distension
         subjects affected / exposed
    14 / 277 (5.05%)
    16 / 279 (5.73%)
         occurrences all number
    15
    21
    Diarrhoea
         subjects affected / exposed
    64 / 277 (23.10%)
    119 / 279 (42.65%)
         occurrences all number
    85
    231
    Stomatitis
         subjects affected / exposed
    16 / 277 (5.78%)
    30 / 279 (10.75%)
         occurrences all number
    18
    31
    Nausea
         subjects affected / exposed
    87 / 277 (31.41%)
    66 / 279 (23.66%)
         occurrences all number
    139
    77
    Dry mouth
         subjects affected / exposed
    20 / 277 (7.22%)
    24 / 279 (8.60%)
         occurrences all number
    21
    27
    Vomiting
         subjects affected / exposed
    49 / 277 (17.69%)
    60 / 279 (21.51%)
         occurrences all number
    84
    83
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    5 / 277 (1.81%)
    20 / 279 (7.17%)
         occurrences all number
    6
    23
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    60 / 277 (21.66%)
    59 / 279 (21.15%)
         occurrences all number
    74
    78
    Rash
         subjects affected / exposed
    17 / 277 (6.14%)
    39 / 279 (13.98%)
         occurrences all number
    17
    44
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    42 / 277 (15.16%)
    136 / 279 (48.75%)
         occurrences all number
    63
    200
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    4 / 277 (1.44%)
    14 / 279 (5.02%)
         occurrences all number
    5
    15
    Hypothyroidism
         subjects affected / exposed
    19 / 277 (6.86%)
    105 / 279 (37.63%)
         occurrences all number
    23
    112
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    8 / 277 (2.89%)
    29 / 279 (10.39%)
         occurrences all number
    8
    30
    Arthralgia
         subjects affected / exposed
    17 / 277 (6.14%)
    50 / 279 (17.92%)
         occurrences all number
    19
    66
    Back pain
         subjects affected / exposed
    26 / 277 (9.39%)
    34 / 279 (12.19%)
         occurrences all number
    29
    37
    Pain in extremity
         subjects affected / exposed
    10 / 277 (3.61%)
    17 / 279 (6.09%)
         occurrences all number
    10
    22
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    15 / 277 (5.42%)
    28 / 279 (10.04%)
         occurrences all number
    17
    39
    COVID-19
         subjects affected / exposed
    12 / 277 (4.33%)
    27 / 279 (9.68%)
         occurrences all number
    12
    29
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    13 / 277 (4.69%)
    34 / 279 (12.19%)
         occurrences all number
    18
    43
    Hypokalaemia
         subjects affected / exposed
    18 / 277 (6.50%)
    20 / 279 (7.17%)
         occurrences all number
    25
    23
    Hyponatraemia
         subjects affected / exposed
    7 / 277 (2.53%)
    19 / 279 (6.81%)
         occurrences all number
    7
    23
    Decreased appetite
         subjects affected / exposed
    69 / 277 (24.91%)
    75 / 279 (26.88%)
         occurrences all number
    95
    90

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Mar 2021
    The primary change of Amendment 1 was to update per country Health Authorities and clarify information
    26 May 2021
    The primary change of Amendment 2 was to update lenvatinib toxicity information in response to a Health Authority request
    29 Aug 2022
    The primary change of Amendment 3 was to clarify metastatic liver subgroup language

    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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    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.

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