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    Clinical Trial Results:
    A Phase 2, Open-Label Study of BGB-A317 in Patients with Relapsed or Refractory Mature T- and NK-cell Neoplasms

    Summary
    EudraCT number
    		 2017-003700-44
    Trial protocol
    		 DE   FR   IT  
    Global end of trial date
    21 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Apr 2022
    First version publication date
    18 Apr 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BGB-A317-207
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03493451
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 -: -
    Sponsors
    Sponsor organisation name
    BeiGene, Ltd., c/o BeiGene USA, Inc.
    Sponsor organisation address
    2955 Campus Drive, Suite 200, San Mateo, United States, 94403
    Public contact
    BeiGene Clinical Support, BeiGene, Ltd., 1 877-828-5568, clinicaltrials@beigene.com
    Scientific contact
    BeiGene Clinical Support, BeiGene, Ltd., 1 877-828-5568, clinicaltrials@beigene.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
    16 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate efficacy of BGB-A317 in subjects with relapsed or refractory mature T- and NK-cell neoplasms as measured by overall response rate and determined by investigator. • For cohorts 1 and 2, overall response rate will be measured using the Lugano criteria (Cheson et al 2014) with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) modification for immunomodulatory drugs (Cheson et al 2016). • For cohort 3, overall response rate will be measured using the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) guidelines (Olsen et al 2011).
    Protection of trial subjects
    This trial was designed and monitored in accordance with Sponsor procedures, which comply with the ethical principles of GCP as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki. The IEC/IRB-approved ICF was signed and dated by the subject or the subject’s legally authorized representative before his or her participation in the study. A copy of each signed ICF was provided to the subject or the subject’s legally authorized representative. All signed and dated ICFs were retained in each patient’s study file or in the site file. For any updated or revised ICFs, written informed consent was obtained using the IEC/IRB-approved updated/revised ICFs for continued participation in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    China: 41
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Italy: 28
    Worldwide total number of subjects
    77
    EEA total number of subjects
    33
    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)
    55
    From 65 to 84 years
    22
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were enrolled from study centers in Canada, China, France, Italy, and Taiwan, China.

    Pre-assignment
    Screening details
    		 Subjects were enrolled into 1 of 3 cohorts in this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: ENKTL
    Arm description
    		 Subjects with relapsed or refractory (R/R) extranodal natural killer-/T-cell lymphoma (ENKTL; nasal or non-nasal type) were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tislelizumab
    Investigational medicinal product code
    Other name
    BGB-A317
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Arm title
    		 Cohort 2: PTCL-NOS, AITL, and ALCL
    Arm description
    		 Subjects with other R/R mature T-cell neoplasms [limited to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tislelizumab
    Investigational medicinal product code
    Other name
    BGB-A317
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Arm title
    		 Cohort 3: MF and SS
    Arm description
    		 Subjects with R/R cutaneous T-cell lymphoma [limited to mycosis fungoides (MF) and Sèzary syndrome (SS)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tislelizumab
    Investigational medicinal product code
    Other name
    BGB-A317
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Number of subjects in period 1
    		Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Started
    22
    44
    11
    Completed
    0
    0
    0
    Not completed
    22
    44
    11
         Consent withdrawn by subject
    1
    1
    2
         Death
    11
    26
    3
         Transferred to long term extension study
    8
    13
    5
         Lost to follow-up
    1
    4
    1
         Progressive disease
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: ENKTL
    Reporting group description
    		 Subjects with relapsed or refractory (R/R) extranodal natural killer-/T-cell lymphoma (ENKTL; nasal or non-nasal type) were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 2: PTCL-NOS, AITL, and ALCL
    Reporting group description
    		 Subjects with other R/R mature T-cell neoplasms [limited to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 3: MF and SS
    Reporting group description
    		 Subjects with R/R cutaneous T-cell lymphoma [limited to mycosis fungoides (MF) and Sèzary syndrome (SS)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS Total
    Number of subjects
    		 22 44 11 77
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 51.5 ( 16.24 ) 55.8 ( 15.03 ) 59.4 ( 12.45 ) -
    Gender categorical
    Units: Subjects
        Female
    		 8 15 3 26
        Male
    		 14 29 8 51
    Race/Ethnicity
    Units: Subjects
        Asian
    		 19 23 2 44
        White
    		 2 18 8 28
        Not reported
    		 1 3 1 5

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: ENKTL
    Reporting group description
    		 Subjects with relapsed or refractory (R/R) extranodal natural killer-/T-cell lymphoma (ENKTL; nasal or non-nasal type) were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 2: PTCL-NOS, AITL, and ALCL
    Reporting group description
    		 Subjects with other R/R mature T-cell neoplasms [limited to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 3: MF and SS
    Reporting group description
    		 Subjects with R/R cutaneous T-cell lymphoma [limited to mycosis fungoides (MF) and Sèzary syndrome (SS)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Primary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR) [1]
    End point description
    ORR is defined as the percentage of subjects achieving a best overall response of complete response or partial response as determined by the investigator using Lugano criteria with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) modification for cohorts 1 and 2 and International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) guidelines for cohort 3.
    End point type
    Primary
    End point timeframe
    Up to approximately 3 years and 1 week
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Two-sided Clopper-Pearson 95% Confidence Intervals are provided for this endpoint
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22
    44
    11
    Units: Percentage of subjects
        number (confidence interval 95%)
    31.8 (13.9 to 54.9)
    20.5 (9.8 to 35.3)
    45.5 (16.7 to 76.6)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR defined as the time from the first determination of an objective response until progression or death, whichever occurs first, as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. Duration of response analysis only included responders (those who achieved partial or complete response).
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    7 [2]
    9 [3]
    5
    Units: Months
        median (confidence interval 95%)
    9999 (2.66 to 9999)
    8.2 (2.50 to 9999)
    11.3 (2.76 to 11.30)
    Notes
    [2] - 9999 = Not estimable due to insufficient number of subjects with events
    [3] - 9999 = Not estimable due to insufficient number of subjects with events
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS)

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    End point title
    		 Progression-free Survival (PFS)
    End point description
    PFS is defined as the time from first study drug administration to the date of disease progression or death, whichever occurs first, as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3.
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22
    44
    11
    Units: Months
        median (confidence interval 95%)
    2.7 (1.45 to 5.32)
    2.7 (2.56 to 4.76)
    16.8 (2.60 to 16.82)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS) [4]
    End point description
    OS defined as the time from first study drug administration to the date of death due to any reason for cohorts 1 and 2.
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only Cohorts 1 and 2 were analysed for this endpoint
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL
    Number of subjects analysed
    22 [5]
    44
    Units: Months
        median (confidence interval 95%)
    8.8 (3.25 to 9999)
    13.3 (7.66 to 26.22)
    Notes
    [5] - 9999 = Not estimable due to insufficient number of subjects with events
    No statistical analyses for this end point

    Secondary: Complete Response Rate (CRR)

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    End point title
    		 Complete Response Rate (CRR)
    End point description
    CRR is defined as the percentage of subjects who achieve complete response or complete metabolic response as best overall response as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3.
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22
    44
    11
    Units: Percentage of subjects
        number (confidence interval 95%)
    18.2 (5.2 to 40.3)
    9.1 (2.5 to 21.7)
    9.1 (0.2 to 41.3)
    No statistical analyses for this end point

    Secondary: Time to Response (TTR)

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    End point title
    		 Time to Response (TTR)
    End point description
    Time to response defined as the time from first study drug administration to the time the response criteria (complete response or partial response) are first met as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. Duration of response analysis only included responders (those who achieved partial or complete response).
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    7
    9
    5
    Units: Months
        median (full range (min-max))
    5.75 (2.1 to 13.9)
    2.86 (2.1 to 5.5)
    6.83 (2.6 to 11.1)
    No statistical analyses for this end point

    Secondary: Quality of Life Assessment: EQ-5D-5L Change from Baseline in Visual Analogue Score

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    End point title
    		 Quality of Life Assessment: EQ-5D-5L Change from Baseline in Visual Analogue Score
    End point description
    Mean change from baseline at safety follow-up visit in EQ-5D-5L visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant’s self-rated health on a scale from 0 to 100, where 100 is ‘the best health you can imagine’ and 0 is ‘the worst health you can imagine.’ An increasing score indicates improvements from baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week)
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22 [6]
    44 [7]
    11 [8]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Cycle 5, Day 1; n=12, 19, 8
    4.42 ( 10.273 )
    1.11 ( 13.884 )
    0.25 ( 22.276 )
        Cycle 9, Day 1; n=6, 9, 6
    1.17 ( 4.916 )
    5.56 ( 21.279 )
    -0.83 ( 17.713 )
        Cycle 13, Day 1; n=7, 5, 6
    -3.29 ( 16.650 )
    15.00 ( 19.685 )
    1.33 ( 21.398 )
        Cycle 17, Day 1; n= 6, 6, 6
    0.17 ( 9.326 )
    10.00 ( 17.889 )
    3.67 ( 23.551 )
        Cycle 21, Day 1; n=4, 3, 4
    4.25 ( 10.905 )
    8.33 ( 22.546 )
    5.50 ( 18.285 )
        Cycle 25, Day 1; n=3, 2, 2
    4.00 ( 14.422 )
    -2.50 ( 10.607 )
    5.00 ( 7.071 )
        Cycle 29, Day 1; n=3, 2, 0
    -2.67 ( 4.619 )
    -5.00 ( 7.071 )
    9999 ( 9999 )
        Cycle 33, Day 1; n=1, 1, 0
    -3.00 ( 9999 )
    0.00 ( 9999 )
    9999 ( 9999 )
        Safety Follow-up; n=14, 23, 2
    -1.50 ( 8.546 )
    -9.52 ( 21.047 )
    12.50 ( 3.536 )
    Notes
    [6] - 9999 = Not estimable due to sample size
    [7] - 9999 = Not estimable due to sample size
    [8] - 9999 = Not estimable due to sample size or no subjects analysed
    No statistical analyses for this end point

    Secondary: Quality of Life Assessment: EORTC QLQ-C30 Change from Baseline in Global Health Status Score

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    End point title
    		 Quality of Life Assessment: EORTC QLQ-C30 Change from Baseline in Global Health Status Score
    End point description
    Mean change from baseline at safety follow-up visit in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. A increasing score indicates improvements from baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week)
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22 [9]
    44 [10]
    11 [11]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Cycle 5, Day 1; n=12, 20, 8
    7.64 ( 24.220 )
    6.67 ( 19.041 )
    10.42 ( 24.296 )
        Cycle 9, Day 1; n=6, 9, 6
    8.33 ( 10.541 )
    12.04 ( 28.294 )
    1.39 ( 21.995 )
        Cycle 13, Day 1; n=7, 5, 6
    4.76 ( 11.644 )
    -1.67 ( 19.003 )
    2.78 ( 15.516 )
        Cycle 17, Day 1; n=6, 6, 6
    2.78 ( 12.546 )
    6.94 ( 30.008 )
    4.17 ( 21.570 )
        Cycle 21, Day 1; n=4, 3, 4
    12.50 ( 14.434 )
    0.00 ( 33.333 )
    0.00 ( 20.412 )
        Cycle 25, Day 1; n=4, 2, 2
    14.58 ( 25.797 )
    -8.33 ( 11.785 )
    -4.17 ( 5.893 )
        Cycle 29, Day 1; n=3, 2, 0
    16.67 ( 16.667 )
    -8.33 ( 11.785 )
    9999 ( 9999 )
        Cycle 33, Day 1; n=1, 1, 0
    0.00 ( 9999 )
    0.00 ( 9999 )
    9999 ( 9999 )
        Safety Follow-up; n=14, 24, 2
    7.74 ( 27.045 )
    -14.93 ( 26.917 )
    20.83 ( 17.678 )
    Notes
    [9] - 9999 = Not estimable due to sample size
    [10] - 9999 = Not estimable due to sample size
    [11] - 9999 = Not estimable due to sample size or no subjects analysed
    No statistical analyses for this end point

    Secondary: Quality of Life Assessment: EORTC QLQ-C30 Change from Baseline in Fatigue Score

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    End point title
    		 Quality of Life Assessment: EORTC QLQ-C30 Change from Baseline in Fatigue Score
    End point description
    Mean change from baseline at safety follow-up visit in EORTC QLQ-C30 Fatigue score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes questions related to fatigue symptoms in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. A increasing score indicates improvements from baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week)
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22 [12]
    44 [13]
    11 [14]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Cycle 5, Day 1; n=12, 19, 8
    -2.78 ( 14.312 )
    7.02 ( 14.912 )
    1.39 ( 41.335 )
        Cycle 9, Day 1; n=6, 8, 6
    0.00 ( 12.172 )
    -1.39 ( 11.011 )
    -22.22 ( 41.574 )
        Cycle 13, Day 1; n=7, 5, 6
    -1.59 ( 11.878 )
    -6.67 ( 12.669 )
    -5.56 ( 18.257 )
        Cycle 17, Day 1; n=6, 6, 6
    9.26 ( 16.355 )
    1.85 ( 10.924 )
    -12.96 ( 16.355 )
        Cycle 21, Day 1; n=4, 3, 4
    0.00 ( 12.830 )
    11.11 ( 11.111 )
    -16.67 ( 14.344 )
        Cycle 25, Day 1; n=4, 2, 2
    0.00 ( 15.713 )
    27.78 ( 7.857 )
    -5.56 ( 7.857 )
        Cycle 29, Day 1; n=3, 2, 0
    3.70 ( 27.962 )
    22.22 ( 15.713 )
    9999 ( 9999 )
        Cycle 33, Day 1; n=1, 1, 0
    11.11 ( 9999 )
    33.33 ( 9999 )
    9999 ( 9999 )
        Safety Follow-up; n=14, 24, 2
    -1.59 ( 19.903 )
    7.87 ( 30.820 )
    -44.44 ( 31.427 )
    Notes
    [12] - 9999 = Not estimable due to sample size
    [13] - 9999 = Not estimable due to sample size
    [14] - 9999 = Not estimable due to sample size or no subjects analysed
    No statistical analyses for this end point

    Secondary: Number of Subjects with Adverse Events

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    End point title
    		 Number of Subjects with Adverse Events
    End point description
    Number of subjects with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically relevant changes in laboratory tests, physical examination, electrocardiogram, and vital signs
    End point type
    Secondary
    End point timeframe
    Up to approximately 3 years and 1 week
    End point values
    		 Cohort 1: ENKTL Cohort 2: PTCL-NOS, AITL, and ALCL Cohort 3: MF and SS
    Number of subjects analysed
    22
    44
    11
    Units: Subjects
        At least one TEAE
    22
    41
    10
        SAEs
    9
    21
    5
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 3 years and 1 week
    Adverse event reporting additional description
    Adverse events were graded by the investigators using Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Cohort 1: ENKTL
    Reporting group description
    		 Subjects with relapsed or refractory (R/R) extranodal natural killer-/T-cell lymphoma (ENKTL; nasal or non-nasal type) were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 3: MF and SS
    Reporting group description
    		 Subjects with R/R cutaneous T-cell lymphoma [limited to mycosis fungoides (MF) and Sèzary syndrome (SS)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Reporting group title
    Cohort 2: PTCL-NOS, AITL, and ALCL
    Reporting group description
    		 Subjects with other R/R mature T-cell neoplasms [limited to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle)

    Serious adverse events
    		 Cohort 1: ENKTL Cohort 3: MF and SS Cohort 2: PTCL-NOS, AITL, and ALCL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 22 (40.91%)
    5 / 11 (45.45%)
    21 / 44 (47.73%)
         number of deaths (all causes)
    11
    3
    26
         number of deaths resulting from adverse events
    1
    1
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour flare
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour rupture
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Tumour ulceration
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Arterial haemorrhage
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    4 / 44 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    4 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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-mediated lung disease
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Interstitial lung disease
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Investigations
    Epstein-Barr virus test positive
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Dizziness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Syncope
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Intussusception
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Nausea
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Vomiting
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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 and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Renal failure
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Renal impairment
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Oral infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    4 / 44 (9.09%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia cryptococcal
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Varicella zoster virus infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (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
    Decreased appetite
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Hypercalcaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (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
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Cohort 1: ENKTL Cohort 3: MF and SS Cohort 2: PTCL-NOS, AITL, and ALCL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 22 (95.45%)
    10 / 11 (90.91%)
    39 / 44 (88.64%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    4
    0
    Tumour flare
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 11 (18.18%)
    2 / 44 (4.55%)
         occurrences all number
    0
    2
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 11 (18.18%)
    8 / 44 (18.18%)
         occurrences all number
    2
    2
    9
    Chest discomfort
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Face oedema
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    2 / 44 (4.55%)
         occurrences all number
    0
    2
    3
    Influenza like illness
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 11 (27.27%)
    1 / 44 (2.27%)
         occurrences all number
    0
    3
    2
    Malaise
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    3
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 22 (9.09%)
    4 / 11 (36.36%)
    3 / 44 (6.82%)
         occurrences all number
    2
    6
    3
    Pyrexia
         subjects affected / exposed
    6 / 22 (27.27%)
    4 / 11 (36.36%)
    13 / 44 (29.55%)
         occurrences all number
    13
    7
    25
    Swelling face
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Cough
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 11 (0.00%)
    7 / 44 (15.91%)
         occurrences all number
    4
    0
    10
    Dyspnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    2 / 44 (4.55%)
         occurrences all number
    0
    1
    3
    Epistaxis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Hiccups
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    3
    Nasal congestion
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Nasal obstruction
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Pharyngeal ulceration
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory acidosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    4 / 44 (9.09%)
         occurrences all number
    0
    1
    4
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    2
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    1
    0
    5
    Alpha hydroxybutyrate dehydrogenase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    4
    0
    3
    Blood albumin decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    3
    Blood bilirubin increased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    5
    0
    2
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    5
    4
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    3 / 44 (6.82%)
         occurrences all number
    0
    1
    6
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    4 / 44 (9.09%)
         occurrences all number
    1
    0
    7
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    2
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    9
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    16
    0
    2
    Platelet count decreased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    4 / 44 (9.09%)
         occurrences all number
    10
    0
    5
    Tri-iodothyronine free decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Weight decreased
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 11 (0.00%)
    4 / 44 (9.09%)
         occurrences all number
    8
    0
    5
    Weight increased
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    11
    0
    2
    White blood cell count decreased
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 11 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    21
    0
    6
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Conduction disorder
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Extrasystoles
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Palpitations
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    2
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    0
    0
    3
    Syncope
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 22 (27.27%)
    0 / 11 (0.00%)
    7 / 44 (15.91%)
         occurrences all number
    14
    0
    8
    Lymph node pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    4
    Lymphadenopathy
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    4
    Neutropenia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    5 / 44 (11.36%)
         occurrences all number
    0
    0
    13
    Thrombocytopenia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    7 / 44 (15.91%)
         occurrences all number
    0
    0
    11
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Deafness unilateral
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    2
    0
    Tinnitus
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    1
    0
    2
    Vertigo
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    2
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Cataract
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    2
    0
    Eversion of lacrimal punctum
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Retinal disorder
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    2
    0
    0
    Retinopathy
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    3
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    2
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 11 (18.18%)
    2 / 44 (4.55%)
         occurrences all number
    2
    2
    2
    Abdominal pain upper
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    2
    Constipation
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 11 (18.18%)
    4 / 44 (9.09%)
         occurrences all number
    0
    2
    4
    Diarrhoea
         subjects affected / exposed
    3 / 22 (13.64%)
    4 / 11 (36.36%)
    4 / 44 (9.09%)
         occurrences all number
    3
    5
    4
    Dyspepsia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    0
    0
    4
    Nausea
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 11 (18.18%)
    1 / 44 (2.27%)
         occurrences all number
    3
    2
    1
    Oral cavity fistula
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 11 (18.18%)
    1 / 44 (2.27%)
         occurrences all number
    3
    2
    1
    Toothache
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    2
    Vomiting
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 11 (27.27%)
    0 / 44 (0.00%)
         occurrences all number
    2
    3
    0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Blood blister
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Circumoral oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis psoriasiform
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    2
    0
    Dry skin
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    5 / 44 (11.36%)
         occurrences all number
    0
    1
    10
    Pruritus
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 11 (27.27%)
    6 / 44 (13.64%)
         occurrences all number
    3
    4
    9
    Rash
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 11 (27.27%)
    2 / 44 (4.55%)
         occurrences all number
    1
    4
    2
    Rash maculo-papular
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    3
    0
    1
    Rash pruritic
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    8
    Skin mass
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    2
    Skin ulcer
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    3
    0
    Urticaria
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    2
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    3
    Hypothyroidism
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 11 (27.27%)
    5 / 44 (11.36%)
         occurrences all number
    1
    4
    5
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 11 (27.27%)
    7 / 44 (15.91%)
         occurrences all number
    5
    5
    18
    Back pain
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    1
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Osteoporosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in jaw
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    2
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    2
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Gingivitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Herpes simplex
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Impetigo
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    2 / 44 (4.55%)
         occurrences all number
    1
    1
    3
    Pharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Pseudomonal skin infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    2
    0
    1
    Skin bacterial infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Skin infection
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    1
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    5 / 44 (11.36%)
         occurrences all number
    2
    0
    8
    Urinary tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    1
    Wound infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    1
    1
    1
    Diabetes mellitus
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Gout
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    4 / 22 (18.18%)
    1 / 11 (9.09%)
    4 / 44 (9.09%)
         occurrences all number
    4
    1
    5
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    5 / 22 (22.73%)
    1 / 11 (9.09%)
    1 / 44 (2.27%)
         occurrences all number
    8
    1
    1
    Hypocalcaemia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 11 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    3
    0
    1
    Hypokalaemia
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 11 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    4
    0
    3
    Hyponatraemia
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 11 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    7
    0
    0
    Impaired fasting glucose
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 11 (9.09%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Dec 2017
    • Decreased the frequency of imaging studies to reduce the radiation exposure and burden to patients and sites • Added a guidance for enrollment holds for Cohorts 1 and 2 • Added LYRIC modification for immunomodulatory therapy for disease response assessment • Clarified some Inclusion and Exclusion Criteria • Added the section of exam of liver, spleen, and lymph nodes to clarify efficacy assessments • Corrected corticosteroid therapy usage and removed hormone replacement, bisphosphonates, and RANKL inhibitors to clarify permitted therapies • Clarified adverse event collection and safety monitoring guidance per guidance from the health authority • Added additional safety assessments (ie, ophthalmologic examinations, thyroid function tests, and pancreatic enzymes) per guidance from the health authority
    23 Aug 2018
    • Updated the compound name to the International Nonproprietary Name (ie, tislelizumab) throughout the protocol • Increased the sample size of Cohort 1 approximately 50 patients to approximately 70 patients for potential regulatory considerations and having adequate power • Updated the protocol according to administrative changes made to other tislelizumab protocols (eg, confidentiality statement and safety reporting language, etc) • Replaced the Safety Monitoring Committee with an IDMC per guidance from the health authority • Clarified that EBV circulating DNA testing were to be done if patients are EBV-positive by EBV encoded RNAs in situ hybridization at screening • Clarified tumor assessment per LYRIC guidelines regarding pseudoprogression and indeterminate response • Clarified that cohorts were to be analyzed separately for the primary efficacy analyses • Added additional requirements for safety assessments (ie, sensitivity requirement for HBV DNA test; inclusion of liver function, creatine kinase, and creatine kinase-cardiac muscle isoenzyme testing; performing pancreatic enzymes and coagulation profile testing when clinically indicated; and clarification of the frequency of ophthalmologic monitoring) per guidance from the health authority • Clarified procedures for patients who continue treatment after study termination • Clarified permitted and prohibited therapy during study treatment • Clarified adverse event collection and safety monitoring guidance per guidance from the health authority • Clarified some Inclusion and Exclusion Criteria
    14 Mar 2019
    • Added a Cohort 3 to enroll patients with MF or SS and updated the description throughout the protocol for the addition of Cohort 3 • Changed the tumor assessment for primary endpoint from “determined by an independent central review” to “by investigators” because the study was no longer a confirmatory study • Updated the protocol according to changes made to other tislelizumab protocols (ie, changed PK and immunogenicity objectives from secondary to exploratory and safety reporting language) • Updated sample size • Specified subtypes of Cohort 2 in the guidance for enrollment holds and efficacy analyses • Exclusion Criteria #4: Clarified that the chemotherapy was meant for systemic treatment and the required washout period for investigational treatment • Changed the minimum amount of time between doses from 14 days to 10 days • Added weekly visits during Cycle 1 for safety assessments per recommendation from IDMC • Clarified that a pump would not be required if infusion speed was controlled through alternative means and consistent with approved institutional procedures • Provided additional diagnostic and treatment recommendations for cytokine release syndrome

    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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