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    Clinical Trial Results:
    An Open-Label, Randomized, Phase 3 Clinical Trial of REGN2810 Versus Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Carcinoma

    Summary
    EudraCT number
    2017-000350-19
    Trial protocol
    ES   PL   GB   BE   GR   IT  
    Global end of trial date
    20 Apr 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    05 May 2024
    First version publication date
    05 May 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    R2810-ONC-1676
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc
    Sponsor organisation address
    777 Old Saw Mill River Road, Tarrytown, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc, 001 844-734-6643, clinicaltrials@regeneron.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
    20 Apr 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Apr 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare overall survival (OS) for participants with recurrent or metastatic cervical cancer who have histology of squamous cell carcinoma (SCC) and who had any eligible histology, treated with either cemiplimab or investigator’s choice (IC) chemotherapy.
    Protection of trial subjects
    It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Sep 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 30
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Brazil: 89
    Country: Number of subjects enrolled
    Canada: 42
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Italy: 35
    Country: Number of subjects enrolled
    Japan: 56
    Country: Number of subjects enrolled
    Korea, Republic of: 76
    Country: Number of subjects enrolled
    Poland: 45
    Country: Number of subjects enrolled
    Russian Federation: 85
    Country: Number of subjects enrolled
    Spain: 66
    Country: Number of subjects enrolled
    Taiwan: 34
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    United States: 24
    Worldwide total number of subjects
    608
    EEA total number of subjects
    170
    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)
    533
    From 65 to 84 years
    73
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    752 participants were screened, 144 participants failed screening, 608 randomized to receive cemiplimab or investigator choice of chemotherapy (control treatment determined before randomization by investigator from options per protocol). Randomization was stratified

    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
    Cemiplimab
    Arm description
    Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
    Arm type
    Experimental

    Investigational medicinal product name
    LIBTAYO
    Investigational medicinal product code
    REGN2810
    Other name
    cemiplimab
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Fixed Dose of 350 mg at a frequency of Day 1, every three weeks

    Arm title
    Investigator Choice (IC) Chemotherapy
    Arm description
    Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
    Arm type
    Active comparator

    Investigational medicinal product name
    Antifolate: Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 mg/m^2, , body surface area Day 1 every 3 weeks for up to 96 weeks

    Investigational medicinal product name
    Topoisomerase 1 inhibitor: toptecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion, Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 mg/m^2 body surface area daily for 5 days, starting on Day 1 for three weeks (up to 96 weeks)

    Investigational medicinal product name
    Vinca alkaloid: Vinorelbine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m^2 for a frequency of Days 1 and 8 for every three weeks, for up to 96 weeks

    Investigational medicinal product name
    Nucleoside analogue: gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose: 1000 mg/m2 body surface area at a frequency of Days 1 and 8 every 3 weeks for up to 96 weeks

    Investigational medicinal product name
    Topoisomerase 1 inhibitor: irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg/m^2 weekly (Days 1, 8, 15, and 22) followed by 10 to 14 days rest, for a 42-day (6-week) cycle for up to 96 weeks

    Number of subjects in period 1
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Started
    304
    304
    Full Analysis Set (FAS)
    304
    304
    Safety Analysis Set (SAF)
    300
    290
    Completed Treatment
    38
    0
    Completed
    35
    0
    Not completed
    269
    304
         Adverse event, serious fatal
    96
    98
         Participant Decision
    35
    43
         Physician decision
    1
    3
         Non-compliance with Study Drug
    -
    2
         Adverse event, non-fatal
    17
    7
         Sponsor Decision
    1
    -
         Unspecified
    -
    2
         Lost to follow-up
    2
    2
         Withdrawal of Participant
    8
    26
         Disease Progression
    109
    121

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cemiplimab
    Reporting group description
    Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Reporting group title
    Investigator Choice (IC) Chemotherapy
    Reporting group description
    Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Reporting group values
    Cemiplimab Investigator Choice (IC) Chemotherapy Total
    Number of subjects
    304 304 608
    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)
    269 264 533
        From 65-84 years
    30 29 59
        85 years and over
    5 11 16
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    51.1 ( 11.59 ) 51.2 ( 11.77 ) -
    Sex: Female, Male
    Units: Participants
        Female
    304 304 608
        Male
    0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    47 44 91
        Not Hispanic or Latino
    251 250 501
        Unknown or Not Reported
    6 10 16
    Race/Ethnicity, Customized
    Units: Subjects
        White
    193 192 385
        Black or African American
    9 12 21
        Asian
    88 88 176
        American Indian or Alaska Native
    2 1 3
        Other
    8 4 12
        Unknown
    1 1 2
        Not Reported
    3 6 9

    End points

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    End points reporting groups
    Reporting group title
    Cemiplimab
    Reporting group description
    Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Reporting group title
    Investigator Choice (IC) Chemotherapy
    Reporting group description
    Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Primary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.
    End point type
    Primary
    End point timeframe
    Time from randomization to the date of death due to any cause (assessed up to 40 months)
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    304
    304
    Units: Months
        median (confidence interval 95%)
    11.7 (9.6 to 13.4)
    8.5 (7.5 to 9.6)
    Statistical analysis title
    Stratified Log-rank Test
    Comparison groups
    Cemiplimab v Investigator Choice (IC) Chemotherapy
    Number of subjects included in analysis
    608
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Stratified Log-rank Test
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.665
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.555
         upper limit
    0.796

    Primary: Overall Survival (OS) in the SCC population

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    End point title
    Overall Survival (OS) in the SCC population
    End point description
    Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact
    End point type
    Primary
    End point timeframe
    Time from randomization to the date of death due to any cause (assessed up to 40 months)
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    239
    238
    Units: Months
        median (confidence interval 95%)
    10.9 (8.9 to 12.9)
    8.8 (7.6 to 9.8)
    Statistical analysis title
    Stratified Log-rank Test
    Comparison groups
    Cemiplimab v Investigator Choice (IC) Chemotherapy
    Number of subjects included in analysis
    477
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00024
    Method
    Stratified Log-rank Test
    Parameter type
    Hazard ratio (HR)
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.57
         upper limit
    0.855

    Secondary: Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

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    End point title
    Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    End point description
    PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who do not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.
    End point type
    Secondary
    End point timeframe
    Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months)
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    304
    304
    Units: Months
        median (confidence interval 95%)
    2.8 (2.6 to 3.9)
    2.9 (2.7 to 3.5)
    Statistical analysis title
    Stratified Log-rank Test
    Comparison groups
    Cemiplimab v Investigator Choice (IC) Chemotherapy
    Number of subjects included in analysis
    608
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.00031
    Method
    Stratified Log-rank Test
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.741
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.623
         upper limit
    0.882

    Secondary: Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1

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    End point title
    Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1
    End point description
    ORR was defined as the number of participants who achieved complete response (CR) or partial response (PR) as per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm) (<1 centimeter [cm]). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From date of randomization up to 40 months
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    304
    304
    Units: Participants
    52
    19
    Statistical analysis title
    Stratified Cochran-Mantel-Haenszel test
    Comparison groups
    Cemiplimab v Investigator Choice (IC) Chemotherapy
    Number of subjects included in analysis
    608
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Stratified Cochran-Mantel-Haenszel test
    Parameter type
    Odds ratio (OR)
    Point estimate
    3.136
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.798
         upper limit
    5.468

    Secondary: Duration of response (DOR) Assessed per RECIST 1.1

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    End point title
    Duration of response (DOR) Assessed per RECIST 1.1
    End point description
    DOR was defined as the time from the date of first response (CR or PR) to the date of the first documented progressive disease (per RECIST 1.1) or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Participants who never progressed while being followed was censored at the last valid tumor measurement. DOR was determined by Kaplan-Meier estimate. Here ‘n’ = the number of evaluable subjects at the specific point in time. Here ‘n’ = the number of evaluable participants
    End point type
    Secondary
    End point timeframe
    Time from the date of first response to the date of the first documented progressive disease or death due to any cause (up to 40 months)
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    52
    19
    Units: Months
        median (confidence interval 95%)
    18.7 (16.4 to 99999)
    7.2 (5.1 to 9.9)
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death

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    End point title
    Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs, serious TEAEs, and TEAEs leading to death were reported. Here ‘n’ = the number of evaluable participants
    End point type
    Secondary
    End point timeframe
    From date of randomization up to 40 months
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    300
    290
    Units: Participants
        Participants with any TEAE
    269
    266
        Participants with any Serious TEAE
    96
    78
        Participants with any TEAE leading to Death
    5
    2
    No statistical analyses for this end point

    Secondary: Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales

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    End point title
    Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales
    End point description
    EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 (“not at all”) to 4 (“very much”) except for the items contributing to the GHS/QoL, which are scored 1 (“very poor”) to 7 (“excellent”). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.
    End point type
    Secondary
    End point timeframe
    From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days)
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    304
    304
    Units: Score on a Scale
    least squares mean (confidence interval 95%)
        Change from Baseline EORTC QLQ-C30 GHS/QoL
    0.46 (-2.715 to 3.642)
    -8.54 (-13.004 to -4.084)
        Baseline Change EORTC QLQ-C30 Physical Functioning
    -0.27 (-3.014 to 2.473)
    -8.86 (-12.517 to -5.196)
    No statistical analyses for this end point

    Secondary: Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade

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    End point title
    Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade
    End point description
    Laboratory parameters included hematology, electrolytes, chemistry (other), and liver function. Clinically significant abnormalities were determined by the investigator based on NCI-CTCAE Grade where Grade 1 = Mild, Grade 2 = moderate, Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. Participants with at least 1 lab abnormality Graded 3/4 in hematology, electrolytes, chemistry (other), or liver function reported. Here ‘n’ = the number of evaluable participants
    End point type
    Secondary
    End point timeframe
    From date of randomization up to 40 months
    End point values
    Cemiplimab Investigator Choice (IC) Chemotherapy
    Number of subjects analysed
    300
    290
    Units: Participants
        Hematology (Grades 3/4)
    84
    137
        Electrolytes (Grades 3/4)
    47
    32
        Chemistry (Other) (Grades 3/4)
    12
    10
        Liver Function (Grades 3/4)
    28
    23
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose up to 40 months
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Chemotherapy*
    Reporting group description
    Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Reporting group title
    Cemiplimab
    Reporting group description
    Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Reporting group title
    Chemotherapy to Cemiplimab*
    Reporting group description
    Treatment until disease progression, unacceptable toxicity, or voluntary withdrawal from the study, or until 96 weeks (16 cycles, each 6 weeks). Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

    Serious adverse events
    Chemotherapy* Cemiplimab Chemotherapy to Cemiplimab*
    Total subjects affected by serious adverse events
         subjects affected / exposed
    84 / 290 (28.97%)
    100 / 300 (33.33%)
    1 / 8 (12.50%)
         number of deaths (all causes)
    249
    234
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolism arterial
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    6 / 290 (2.07%)
    4 / 300 (1.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    3 / 7
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site thrombosis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Hyperpyrexia
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue inflammation
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contrast media allergy
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine haemorrhage
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    2 / 290 (0.69%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    2 / 290 (0.69%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cough
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 290 (0.34%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Personality change
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 290 (0.34%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Cystitis radiation
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device use error
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    2 / 290 (0.69%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural nausea
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune pericarditis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    2 / 290 (0.69%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 290 (4.83%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    15 / 19
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    6 / 290 (2.07%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    5 / 6
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    3 / 290 (1.03%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    3 / 290 (1.03%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Haematochezia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 290 (1.03%)
    2 / 300 (0.67%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 290 (0.69%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 290 (0.69%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 290 (0.34%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 290 (1.03%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic fistula
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral papule
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal perforation
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 290 (0.00%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 290 (0.00%)
    4 / 300 (1.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    3 / 290 (1.03%)
    5 / 300 (1.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 290 (0.69%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 290 (0.34%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 290 (0.00%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postrenal failure
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Secondary adrenocortical insufficiency
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Spondylolisthesis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    11 / 290 (3.79%)
    15 / 300 (5.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 19
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 290 (1.03%)
    5 / 300 (1.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Catheter site infection
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 290 (0.69%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    2 / 290 (0.69%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    3 / 290 (1.03%)
    4 / 300 (1.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected lymphocele
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 290 (0.34%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxic shock syndrome streptococcal
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 290 (0.34%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 290 (0.00%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral rash
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyomyositis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 290 (0.00%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stoma site infection
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 290 (0.00%)
    1 / 300 (0.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 290 (0.34%)
    0 / 300 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Chemotherapy* Cemiplimab Chemotherapy to Cemiplimab*
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    253 / 290 (87.24%)
    239 / 300 (79.67%)
    4 / 8 (50.00%)
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    16 / 290 (5.52%)
    22 / 300 (7.33%)
    0 / 8 (0.00%)
         occurrences all number
    16
    22
    0
    Fatigue
         subjects affected / exposed
    45 / 290 (15.52%)
    52 / 300 (17.33%)
    0 / 8 (0.00%)
         occurrences all number
    81
    54
    0
    Asthenia
         subjects affected / exposed
    45 / 290 (15.52%)
    35 / 300 (11.67%)
    0 / 8 (0.00%)
         occurrences all number
    63
    37
    0
    Pyrexia
         subjects affected / exposed
    62 / 290 (21.38%)
    36 / 300 (12.00%)
    2 / 8 (25.00%)
         occurrences all number
    117
    54
    2
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    6 / 290 (2.07%)
    15 / 300 (5.00%)
    0 / 8 (0.00%)
         occurrences all number
    9
    16
    0
    Pelvic pain
         subjects affected / exposed
    16 / 290 (5.52%)
    13 / 300 (4.33%)
    0 / 8 (0.00%)
         occurrences all number
    16
    14
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    18 / 290 (6.21%)
    27 / 300 (9.00%)
    0 / 8 (0.00%)
         occurrences all number
    22
    28
    0
    Cough
         subjects affected / exposed
    21 / 290 (7.24%)
    20 / 300 (6.67%)
    0 / 8 (0.00%)
         occurrences all number
    28
    25
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    17 / 290 (5.86%)
    20 / 300 (6.67%)
    0 / 8 (0.00%)
         occurrences all number
    18
    21
    0
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    17 / 290 (5.86%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences all number
    35
    3
    0
    Blood creatinine increased
         subjects affected / exposed
    16 / 290 (5.52%)
    19 / 300 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    16
    26
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    19 / 290 (6.55%)
    14 / 300 (4.67%)
    0 / 8 (0.00%)
         occurrences all number
    25
    19
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    20 / 290 (6.90%)
    14 / 300 (4.67%)
    0 / 8 (0.00%)
         occurrences all number
    26
    14
    0
    Neutrophil count decreased
         subjects affected / exposed
    26 / 290 (8.97%)
    3 / 300 (1.00%)
    0 / 8 (0.00%)
         occurrences all number
    64
    7
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    13 / 290 (4.48%)
    8 / 300 (2.67%)
    1 / 8 (12.50%)
         occurrences all number
    38
    8
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    18 / 290 (6.21%)
    22 / 300 (7.33%)
    0 / 8 (0.00%)
         occurrences all number
    19
    43
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    15 / 290 (5.17%)
    2 / 300 (0.67%)
    0 / 8 (0.00%)
         occurrences all number
    17
    2
    0
    Neutropenia
         subjects affected / exposed
    45 / 290 (15.52%)
    9 / 300 (3.00%)
    0 / 8 (0.00%)
         occurrences all number
    75
    11
    0
    Anaemia
         subjects affected / exposed
    128 / 290 (44.14%)
    79 / 300 (26.33%)
    0 / 8 (0.00%)
         occurrences all number
    161
    99
    0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    22 / 290 (7.59%)
    12 / 300 (4.00%)
    0 / 8 (0.00%)
         occurrences all number
    24
    12
    0
    Nausea
         subjects affected / exposed
    100 / 290 (34.48%)
    63 / 300 (21.00%)
    0 / 8 (0.00%)
         occurrences all number
    175
    74
    0
    Diarrhoea
         subjects affected / exposed
    41 / 290 (14.14%)
    35 / 300 (11.67%)
    1 / 8 (12.50%)
         occurrences all number
    60
    61
    1
    Constipation
         subjects affected / exposed
    58 / 290 (20.00%)
    46 / 300 (15.33%)
    1 / 8 (12.50%)
         occurrences all number
    64
    50
    1
    Vomiting
         subjects affected / exposed
    66 / 290 (22.76%)
    49 / 300 (16.33%)
    0 / 8 (0.00%)
         occurrences all number
    101
    65
    0
    Abdominal pain
         subjects affected / exposed
    34 / 290 (11.72%)
    28 / 300 (9.33%)
    0 / 8 (0.00%)
         occurrences all number
    52
    31
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    15 / 290 (5.17%)
    18 / 300 (6.00%)
    0 / 8 (0.00%)
         occurrences all number
    15
    19
    0
    Rash
         subjects affected / exposed
    19 / 290 (6.55%)
    19 / 300 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    22
    29
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 290 (0.00%)
    17 / 300 (5.67%)
    0 / 8 (0.00%)
         occurrences all number
    0
    17
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 290 (0.00%)
    9 / 300 (3.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    9
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    8 / 290 (2.76%)
    18 / 300 (6.00%)
    0 / 8 (0.00%)
         occurrences all number
    9
    20
    0
    Arthralgia
         subjects affected / exposed
    8 / 290 (2.76%)
    33 / 300 (11.00%)
    0 / 8 (0.00%)
         occurrences all number
    11
    38
    0
    Back pain
         subjects affected / exposed
    28 / 290 (9.66%)
    33 / 300 (11.00%)
    0 / 8 (0.00%)
         occurrences all number
    29
    37
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    18 / 290 (6.21%)
    27 / 300 (9.00%)
    0 / 8 (0.00%)
         occurrences all number
    25
    36
    0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 290 (0.00%)
    0 / 300 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    46 / 290 (15.86%)
    46 / 300 (15.33%)
    0 / 8 (0.00%)
         occurrences all number
    55
    49
    0
    Hyperglycaemia
         subjects affected / exposed
    16 / 290 (5.52%)
    4 / 300 (1.33%)
    0 / 8 (0.00%)
         occurrences all number
    21
    4
    0
    Hypokalaemia
         subjects affected / exposed
    17 / 290 (5.86%)
    22 / 300 (7.33%)
    0 / 8 (0.00%)
         occurrences all number
    20
    23
    0
    Hypoalbuminaemia
         subjects affected / exposed
    19 / 290 (6.55%)
    23 / 300 (7.67%)
    0 / 8 (0.00%)
         occurrences all number
    19
    26
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Aug 2018
    Global Amendment 4
    08 Mar 2019
    Global Amendment 5
    27 May 2020
    Global Amendment 6
    14 Apr 2021
    Global Amendment 7

    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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    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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