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    Clinical Trial Results:
    A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in Patients With Locally Advanced, Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer Whose Disease Has Not Progressed After Concurrent Chemoradiotherapy

    Summary
    EudraCT number
    		 2020-004656-14
    Trial protocol
    		 FR   DE   NL   PL   ES   IT  
    Global end of trial date
    17 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Oct 2024
    First version publication date
    25 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BGB-A317-A1217-301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04866017
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    BeiGene
    Sponsor organisation address
    1840 Gateway Drive, San Mateo, CA , United States, 94404
    Public contact
    BeiGene Clinical Support, BeiGene USA, Inc., 1 877-828-5568, ClinicalTrials@beigene.com
    Scientific contact
    BeiGene Clinical Support, BeiGene USA, Inc., 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
    17 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Oct 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the safety and efficacy of ociperlimab in combination with tislelizumab compared to durvalumab in adults with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.
    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
    17 Jun 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 45
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    United States: 4
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Spain: 5
    Worldwide total number of subjects
    63
    EEA total number of subjects
    5
    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)
    33
    From 65 to 84 years
    30
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled in multiple study centers in Taiwan, China, Spain , United States, and Australia. The first participant was consented on June 17th, 2021, and the last participant completed on October 17th, 2023. The decision to terminate the study was made on July 11th, 2023.

    Pre-assignment
    Screening details
    		 This study began under Protocol Amendment (PA) 1. PA 2 was later introduced, but no participants enrolled under it before the study ended. PA 2 revised eligibility criteria, treatment, objectives, and endpoints, and excluded participants from PA 1 in the primary and secondary efficacy analyses.

    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
    		 Ociperlimab + Tislelizumab + cCRT
    Arm description
    		 Participants enrolled in PA 1 received two cycles of ociperlimab (900 mg) and tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). Chemotherapy regimens varied based on investigator discretion, including options such as cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. After the cCRT phase, participants continued ociperlimab and tislelizumab treatment for up to one year.
    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
    200 mg intravenously every three weeks

    Investigational medicinal product name
    Ociperlimab
    Investigational medicinal product code
    Other name
    BGB-A1217
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    900 milligrams (mg) intravenously every three weeks

    Arm title
    		 Tislelizumab + cCRT
    Arm description
    		 Participants in PA 1 received two cycles of tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). The chemotherapy regimen was determined by the investigator and included options like cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. Following the cCRT phase, participants continued tislelizumab treatment for up to one year.
    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
    200 mg intravenously every three weeks

    Arm title
    		 cCRT Followed by Durvalumab
    Arm description
    		 Participants in PA 1 received two cycles of concurrent chemoradiotherapy (cCRT), followed by durvalumab (10 mg/kg intravenously every 2 weeks, or 1500 mg every 4 weeks if locally approved). The chemotherapy regimen was chosen by the investigator and included options such as cisplatin with etoposide, carboplatin with paclitaxel, or pemetrexed with a platinum agent for non-squamous histology; alongside radiotherapy. After cCRT, participants continued durvalumab treatment for up to one year.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    10 milligrams per kilogram (mg/kg) intravenously once every 2 weeks (or 1500 mg intravenously once every 4 weeks where the dosage has been approved by a local health authority)

    Number of subjects in period 1
    		Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Started
    22
    19
    22
    Treated
    22
    18
    22
    Completed
    0
    0
    0
    Not completed
    22
    19
    22
         Consent withdrawn by subject
    1
    -
    1
         Physician decision
    -
    1
    -
         Death
    8
    4
    8
         Study Terminated by Sponsor
    13
    14
    13

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ociperlimab + Tislelizumab + cCRT
    Reporting group description
    		 Participants enrolled in PA 1 received two cycles of ociperlimab (900 mg) and tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). Chemotherapy regimens varied based on investigator discretion, including options such as cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. After the cCRT phase, participants continued ociperlimab and tislelizumab treatment for up to one year.

    Reporting group title
    Tislelizumab + cCRT
    Reporting group description
    		 Participants in PA 1 received two cycles of tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). The chemotherapy regimen was determined by the investigator and included options like cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. Following the cCRT phase, participants continued tislelizumab treatment for up to one year.

    Reporting group title
    cCRT Followed by Durvalumab
    Reporting group description
    		 Participants in PA 1 received two cycles of concurrent chemoradiotherapy (cCRT), followed by durvalumab (10 mg/kg intravenously every 2 weeks, or 1500 mg every 4 weeks if locally approved). The chemotherapy regimen was chosen by the investigator and included options such as cisplatin with etoposide, carboplatin with paclitaxel, or pemetrexed with a platinum agent for non-squamous histology; alongside radiotherapy. After cCRT, participants continued durvalumab treatment for up to one year.

    Reporting group values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab Total
    Number of subjects
    		 22 19 22 63
    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
    The Intent-to-Treat (ITT) Analysis Set is defined as all randomized participants.
    Units: years
        arithmetic mean (standard deviation)
    		 63.4 ( 7.51 ) 62.4 ( 9.27 ) 64.1 ( 7.36 ) -
    Gender categorical
    The Intent-to-Treat (ITT) Analysis Set is defined as all randomized participants.
    Units: Subjects
        Female
    		 3 5 0 8
        Male
    		 19 14 22 55

    End points

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    End points reporting groups
    Reporting group title
    Ociperlimab + Tislelizumab + cCRT
    Reporting group description
    		 Participants enrolled in PA 1 received two cycles of ociperlimab (900 mg) and tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). Chemotherapy regimens varied based on investigator discretion, including options such as cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. After the cCRT phase, participants continued ociperlimab and tislelizumab treatment for up to one year.

    Reporting group title
    Tislelizumab + cCRT
    Reporting group description
    		 Participants in PA 1 received two cycles of tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). The chemotherapy regimen was determined by the investigator and included options like cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. Following the cCRT phase, participants continued tislelizumab treatment for up to one year.

    Reporting group title
    cCRT Followed by Durvalumab
    Reporting group description
    		 Participants in PA 1 received two cycles of concurrent chemoradiotherapy (cCRT), followed by durvalumab (10 mg/kg intravenously every 2 weeks, or 1500 mg every 4 weeks if locally approved). The chemotherapy regimen was chosen by the investigator and included options such as cisplatin with etoposide, carboplatin with paclitaxel, or pemetrexed with a platinum agent for non-squamous histology; alongside radiotherapy. After cCRT, participants continued durvalumab treatment for up to one year.

    Primary: Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

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    End point title
    		 Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC) [1]
    End point description
    PFS is defined as the time from the date of randomization to the date of first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death, whichever occurred first. The primary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Primary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [2] - No participants were enrolled under PA 2.
    [3] - No participants were enrolled under PA 2.
    [4] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Defined as the time from the date of randomization until the date of death due to any cause. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [5] - No participants were enrolled under PA 2.
    [6] - No participants were enrolled under PA 2.
    [7] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR)
    End point description
    Defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) assessed by both the IRC and investigators per RECIST v1.1. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    Units: Percentage of Participants
        number (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [8] - No participants were enrolled under PA 2.
    [9] - No participants were enrolled under PA 2.
    [10] - No participants were enrolled under PA 2.
    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
    Defined as the time from the first determination of a confirmed objective response assessed by both the IRC and investigators per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [11]
    0 [12]
    0 [13]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [11] - No participants were enrolled under PA 2.
    [12] - No participants were enrolled under PA 2.
    [13] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator

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    End point title
    		 Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator
    End point description
    defined as the time from the date of randomization until the first date of distant metastasis assessed by both the IRC and investigators, or death. Distant metastasis is defined as any new lesion that is outside of the radiation field per RECIST v1.1 or proven by biopsy. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [14] - No participants were enrolled under PA 2.
    [15] - No participants were enrolled under PA 2.
    [16] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival 2 (PFS2)

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    End point title
    		 Progression-Free Survival 2 (PFS2)
    End point description
    Defined as the time from randomization to the disease progression after next line of treatment, or death from any cause, whichever occurs first. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [17]
    0 [18]
    0 [19]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [17] - No participants were enrolled under PA 2.
    [18] - No participants were enrolled under PA 2.
    [19] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing Adverse Events (AEs)

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    End point title
    		 Number of Participants Experiencing Adverse Events (AEs)
    End point description
    Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0). The Safety Analysis Set included all randomized patients who received any dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months)
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    22
    18
    22
    Units: Count of Participants
    number (not applicable)
        TEAEs
    22
    18
    22
        SAEs
    11
    8
    8
    No statistical analyses for this end point

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

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    End point title
    		 Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status
    End point description
    Mean change from baseline 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 participants with cancer. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    Every 2 Cycles (6 weeks) until End of Treatment (each cycle is 21 days)
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [20]
    0 [21]
    0 [22]
    Units: Score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [20] - No participants were enrolled under PA 2.
    [21] - No participants were enrolled under PA 2.
    [22] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire‐Lung Cancer 13 (QLQ-LC13)

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    End point title
    		 Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire‐Lung Cancer 13 (QLQ-LC13)
    End point description
    Mean change from baseline in QLQ-CL13 scores for coughing, dyspnea, and chest pain. The QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is “not at all” and 4 is “very much”. Raw scores are transformed into a 0 to 100 scale via linear transformation. A lower score indicates an improvement in symptoms. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    Every 2 Cycles (6 weeks) until End of Treatment (each cycle is 21 days)
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [23]
    0 [24]
    0 [25]
    Units: Score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [23] - No participants were enrolled under PA 2.
    [24] - No participants were enrolled under PA 2.
    [25] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)

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    End point title
    		 Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)
    End point description
    The EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the participant's health state. This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    Every 2 Cycles (6 weeks) until End of Treatment (each cycle is 21 days)
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [26]
    0 [27]
    0 [28]
    Units: Score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [26] - No participants were enrolled under PA 2.
    [27] - No participants were enrolled under PA 2.
    [28] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Secondary: Serum Concentration of Ociperlimab

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    End point title
    		 Serum Concentration of Ociperlimab [29]
    End point description
    Serum concentrations of ociperlimab were measured for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date the investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. The Pharmacokinetics (PK) Analysis Set includes all patients who receive any dose of any component of study drugs and for whom any postdose PK data are available.
    End point type
    Secondary
    End point timeframe
    Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1, 5 and EOT visit (Each Cycle was 21 days)
    Notes
    [29] - 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: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Ociperlimab + Tislelizumab + cCRT
    Number of subjects analysed
    22
    Units: ug/ml
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Predose
    18 ( 0000 )
        Cycle 1 Day 1 Postdose
    312 ( 45.82 )
        Cycle 2 Day 1 Predose
    34.54 ( 63.19 )
        Cycle 2 Day 1 Postdose
    0 ( 0 )
        Cycle 5 Day 1 Predose
    74.86 ( 61.76 )
        Cycle 5 Day 1 Postdose
    339.31 ( 38.21 )
        Cycle 9 Day 1 Predose
    52.4 ( 82.40 )
        Cycle 9 Day 1 Postdose
    0 ( 0 )
        Cycle 17 Day 1 Predose
    81.35 ( 53.83 )
        Cycle 17 Day 1 Postdose
    0 ( 0 )
        End of Treatment
    94.94 ( 232.05 )
    No statistical analyses for this end point

    Secondary: Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group

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    End point title
    		 Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group [30]
    End point description
    Serum concentrations of tislelizumab were collected for participants in the Ociperlimab + Tislelizumab + cCRT treatment group at predose (within 60 minutes before starting infusion) and postdose (within 30 minutes after the end of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. The Pharmacokinetics (PK) Analysis Set includes all patients who receive any dose of any component of study drugs and for whom any postdose PK data are available.
    End point type
    Secondary
    End point timeframe
    Predose at Day 1 of Cycles 1, 2, 5, 9, 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (each cycle was 21 days)
    Notes
    [30] - 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: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Ociperlimab + Tislelizumab + cCRT
    Number of subjects analysed
    22
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Predose
    9999 ( 9999 )
        Cycle 1 Day 1 Postdose
    72.20 ( 26.27 )
        Cycle 2 Day 1 Predose
    15.91 ( 78.83 )
        Cycle 2 Day 1 Postdose
    0 ( 0 )
        Cycle 5 Day 1 Predose
    34.10 ( 49.67 )
        Cycle 5 Day 1 Postdose
    97.08 ( 23.09 )
        Cycle 9 Day 1 Predose
    30.22 ( 55.34 )
        Cycle 9 Day 1 Postdose
    0 ( 0 )
        Cycle 17 Day 1 Predose
    32.24 ( 156.53 )
        Cycle 17 Day 1 Postdose
    0 ( 0 )
        End of Treatment
    49.55 ( 89.19 )
    No statistical analyses for this end point

    Secondary: Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group

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    End point title
    		 Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group [31]
    End point description
    Serum concentrations of tislelizumab were collected for participants in the Tislelizumab + cCRT treatment group at predose (within 60 minutes prior to infusion initiation) and postdose (within 30 minutes after the completion of infusion). End of Treatment (EOT) visits occurred within 7 days after the date investigator determined that study treatment would no longer be used, or before the initiation of a new anticancer treatment, whichever occurred first. PK Analysis Set; Tislelizumab concentration data are reported here for participants in the Tislelizumab + cCRT treatment group. Only participants with available data are included at each time point.
    End point type
    Secondary
    End point timeframe
    Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (Each Cycle is 21 days)
    Notes
    [31] - 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: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Tislelizumab + cCRT
    Number of subjects analysed
    17
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Predose
    0000 ( 0000 )
        Cycle 1 Day 1 Postdose
    73.41 ( 18.53 )
        Cycle 2 Day 1 Predose
    19.69 ( 27.01 )
        Cycle 2 Day 1 Postdose
    0 ( 0 )
        Cycle 5 Day 1 Predose
    37.64 ( 47.00 )
        Cycle 5 Day 1 Postdose
    100.26 ( 29.25 )
        Cycle 9 Day 1 Predose
    36.98 ( 39.63 )
        Cycle 9 Day 1 Postdose
    0 ( 0 )
        Cycle 17 Day 1 Predose
    41.29 ( 55.41 )
        Cycle 17 Day 1 Postdose
    0 ( 0 )
        End of Treatment
    40.18 ( 139.51 )
    No statistical analyses for this end point

    Secondary: Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)

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    End point title
    		 Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) [32]
    End point description
    Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (ociperlimab and tislelizumab). The Immunogenicity Analysis Set includes all participants who received any dose of any component of study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline ADA result were available.
    End point type
    Secondary
    End point timeframe
    Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days). Maximum number of treatment cycles was 19
    Notes
    [32] - 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: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Ociperlimab + Tislelizumab + cCRT
    Number of subjects analysed
    20
    Units: Count of Participants
        number (not applicable)
    0
    No statistical analyses for this end point

    Secondary: Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)

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    End point title
    		 Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs) [33]
    End point description
    Defined as the sum of treatment-boosted and treatment-induced ADA participants as a proportion percentage of the ADA-evaluable participants population and is synonymous with 'ADA Incidence'. ADA samples were collected for participants randomized to Arm A (Ociperlimab + Tislelizumab + cCRT) and Arm B (Tislelizumab + cCRT). The Immunogenicity Analysis Set includes all participants who received any dose of any component of study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline ADA result were available.
    End point type
    Secondary
    End point timeframe
    Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days, maximum number of treatment cycles was 19)
    Notes
    [33] - 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: Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT
    Number of subjects analysed
    20
    17
    Units: Count of Participants
        number (not applicable)
    10
    5
    No statistical analyses for this end point

    Secondary: Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues

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    End point title
    		 Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues
    End point description
    This secondary endpoint was specified in PA 2 and excludes participants enrolled under PA 1. No participants were enrolled under PA 2.
    End point type
    Secondary
    End point timeframe
    From randomization through to the end of study, planned duration was 20 months
    End point values
    		 Ociperlimab + Tislelizumab + cCRT Tislelizumab + cCRT cCRT Followed by Durvalumab
    Number of subjects analysed
    0 [34]
    0 [35]
    0 [36]
    Units: Count of Participants
        number (not applicable)
    Notes
    [34] - No participants were enrolled under PA 2.
    [35] - No participants were enrolled under PA 2.
    [36] - No participants were enrolled under PA 2.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months)
    Adverse event reporting additional description
    All-cause mortality is reported for all randomized participants. Serious and other adverse events include all randomized participants who received ≥ 1 dose of any study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26
    Reporting groups
    Reporting group title
    Ociperlimab + Tislelizumab + cCRT
    Reporting group description
    		 Participants enrolled in PA 1 received two cycles of ociperlimab (900 mg) and tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). Chemotherapy regimens varied based on investigator discretion, including options such as cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. After the cCRT phase, participants continued ociperlimab and tislelizumab treatment for up to one year.

    Reporting group title
    cCRT Followed by Durvalumab
    Reporting group description
    		 Participants in PA 1 received two cycles of concurrent chemoradiotherapy (cCRT), followed by durvalumab (10 mg/kg intravenously every 2 weeks, or 1500 mg every 4 weeks if locally approved). The chemotherapy regimen was chosen by the investigator and included options such as cisplatin with etoposide, carboplatin with paclitaxel, or pemetrexed with a platinum agent for non-squamous histology; alongside radiotherapy. After cCRT, participants continued durvalumab treatment for up to one year.

    Reporting group title
    Tislelizumab + cCRT
    Reporting group description
    		 Participants in PA 1 received two cycles of tislelizumab (200 mg) intravenously every three weeks, combined with concurrent chemoradiotherapy (cCRT). The chemotherapy regimen was determined by the investigator and included options like cisplatin with etoposide, carboplatin with paclitaxel, or platinum-based regimens with pemetrexed for non-squamous histology; alongside radiotherapy. Following the cCRT phase, participants continued tislelizumab treatment for up to one year.

    Serious adverse events
    		 Ociperlimab + Tislelizumab + cCRT cCRT Followed by Durvalumab Tislelizumab + cCRT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 22 (50.00%)
    8 / 22 (36.36%)
    8 / 18 (44.44%)
         number of deaths (all causes)
    8
    8
    4
         number of deaths resulting from adverse events
    1
    2
    1
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    Platelet count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    Transaminases increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    White blood cell count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Infected neoplasm
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Injury, poisoning and procedural complications
    Radiation oesophagitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Radiation pneumonitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    Respiratory, thoracic and mediastinal disorders
    Bronchopleural fistula
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Cough
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    Interstitial lung disease
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Pulmonary embolism
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Pathological fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (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
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         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%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (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
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         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
    		 Ociperlimab + Tislelizumab + cCRT cCRT Followed by Durvalumab Tislelizumab + cCRT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 22 (100.00%)
    22 / 22 (100.00%)
    18 / 18 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Cancer pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Hypotension
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    Hypertension
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    3
    2
    2
    Haematoma
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Flushing
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Aortic arteriosclerosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 22 (18.18%)
    5 / 22 (22.73%)
    1 / 18 (5.56%)
         occurrences all number
    4
    5
    1
    Chest discomfort
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    1
    Facial pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Chills
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    Chest pain
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    3
    2
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 22 (13.64%)
    0 / 18 (0.00%)
         occurrences all number
    1
    4
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Malaise
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    4
    0
    0
    Fatigue
         subjects affected / exposed
    4 / 22 (18.18%)
    2 / 22 (9.09%)
    4 / 18 (22.22%)
         occurrences all number
    5
    2
    5
    Puncture site pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 22 (0.00%)
    4 / 18 (22.22%)
         occurrences all number
    5
    0
    7
    Swelling face
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    1
    0
    2
    Hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    Atelectasis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Cough
         subjects affected / exposed
    4 / 22 (18.18%)
    5 / 22 (22.73%)
    5 / 18 (27.78%)
         occurrences all number
    5
    6
    6
    Epistaxis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    4 / 22 (18.18%)
    2 / 22 (9.09%)
    2 / 18 (11.11%)
         occurrences all number
    4
    2
    2
    Dysphonia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Haemoptysis
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
    3 / 18 (16.67%)
         occurrences all number
    2
    4
    3
    Hiccups
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 22 (13.64%)
    2 / 18 (11.11%)
         occurrences all number
    4
    4
    4
    Hydrothorax
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Immune-mediated lung disease
         subjects affected / exposed
    3 / 22 (13.64%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    1
    Increased viscosity of bronchial secretion
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Interstitial lung disease
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 22 (13.64%)
    2 / 18 (11.11%)
         occurrences all number
    3
    3
    2
    Pleural effusion
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Pleural thickening
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumonitis
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    2
    2
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Pulmonary oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    2 / 18 (11.11%)
         occurrences all number
    0
    2
    3
    Psychiatric disorders
    Tic
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Insomnia
         subjects affected / exposed
    3 / 22 (13.64%)
    1 / 22 (4.55%)
    3 / 18 (16.67%)
         occurrences all number
    4
    1
    3
    Depression
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    2 / 18 (11.11%)
         occurrences all number
    3
    1
    3
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 22 (27.27%)
    4 / 22 (18.18%)
    0 / 18 (0.00%)
         occurrences all number
    10
    5
    0
    Blood bilirubin unconjugated increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 22 (36.36%)
    6 / 22 (27.27%)
    0 / 18 (0.00%)
         occurrences all number
    15
    9
    0
    Amylase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Blood chloride decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    4
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    2
    1
    4
    Blood fibrinogen increased
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    4
    3
    2
    Blood creatinine decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    2
    3
    2
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Blood urea increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    3
    0
    4
    Ejection fraction decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    3
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
    3 / 18 (16.67%)
         occurrences all number
    4
    2
    7
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    2
    Lymphocyte count decreased
         subjects affected / exposed
    5 / 22 (22.73%)
    6 / 22 (27.27%)
    5 / 18 (27.78%)
         occurrences all number
    7
    10
    5
    Neutrophil count decreased
         subjects affected / exposed
    14 / 22 (63.64%)
    13 / 22 (59.09%)
    5 / 18 (27.78%)
         occurrences all number
    31
    29
    13
    Myoglobin blood increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    8 / 22 (36.36%)
    10 / 22 (45.45%)
    5 / 18 (27.78%)
         occurrences all number
    12
    16
    6
    Occult blood positive
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Weight increased
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 22 (13.64%)
    1 / 18 (5.56%)
         occurrences all number
    6
    3
    1
    Weight decreased
         subjects affected / exposed
    4 / 22 (18.18%)
    4 / 22 (18.18%)
    2 / 18 (11.11%)
         occurrences all number
    4
    4
    2
    Troponin T increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 22 (18.18%)
    2 / 18 (11.11%)
         occurrences all number
    1
    4
    2
    Red blood cell count decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Protein total decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    2
    White blood cell count increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    15 / 22 (68.18%)
    13 / 22 (59.09%)
    10 / 18 (55.56%)
         occurrences all number
    45
    41
    25
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Fall
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Infusion related reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    1
    Radiation fibrosis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Radiation pneumonitis
         subjects affected / exposed
    0 / 22 (0.00%)
    5 / 22 (22.73%)
    2 / 18 (11.11%)
         occurrences all number
    0
    7
    2
    Radiation oesophagitis
         subjects affected / exposed
    6 / 22 (27.27%)
    9 / 22 (40.91%)
    3 / 18 (16.67%)
         occurrences all number
    6
    10
    3
    Skin abrasion
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Radiation skin injury
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    5 / 18 (27.78%)
         occurrences all number
    2
    1
    5
    Cardiac disorders
    Bundle branch block left
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Bundle branch block right
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    2
    Sinus bradycardia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    3
    0
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    1
    2
    1
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Dizziness
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 22 (13.64%)
    0 / 18 (0.00%)
         occurrences all number
    2
    6
    0
    Dysgeusia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    Seizure
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    12 / 22 (54.55%)
    14 / 22 (63.64%)
    10 / 18 (55.56%)
         occurrences all number
    14
    20
    15
    Hypercoagulation
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Hyperfibrinogenaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Leukocytosis
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    Leukopenia
         subjects affected / exposed
    2 / 22 (9.09%)
    4 / 22 (18.18%)
    2 / 18 (11.11%)
         occurrences all number
    4
    9
    7
    Lymphopenia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Neutropenia
         subjects affected / exposed
    3 / 22 (13.64%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    4
    1
    3
    Thrombocytosis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    3
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Constipation
         subjects affected / exposed
    9 / 22 (40.91%)
    8 / 22 (36.36%)
    5 / 18 (27.78%)
         occurrences all number
    12
    10
    9
    Colitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 22 (13.64%)
    5 / 22 (22.73%)
    4 / 18 (22.22%)
         occurrences all number
    3
    7
    4
    Dysphagia
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    3
    2
    0
    Dyspepsia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Gingival swelling
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 22 (0.00%)
    5 / 18 (27.78%)
         occurrences all number
    3
    0
    5
    Nausea
         subjects affected / exposed
    6 / 22 (27.27%)
    11 / 22 (50.00%)
    7 / 18 (38.89%)
         occurrences all number
    7
    18
    8
    Odynophagia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Oesophagitis
         subjects affected / exposed
    4 / 22 (18.18%)
    4 / 22 (18.18%)
    4 / 18 (22.22%)
         occurrences all number
    4
    4
    4
    Paraesthesia oral
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    Stomatitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Toothache
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 22 (13.64%)
    0 / 18 (0.00%)
         occurrences all number
    1
    4
    0
    Vomiting
         subjects affected / exposed
    2 / 22 (9.09%)
    4 / 22 (18.18%)
    1 / 18 (5.56%)
         occurrences all number
    2
    5
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    3 / 22 (13.64%)
    7 / 22 (31.82%)
    4 / 18 (22.22%)
         occurrences all number
    3
    7
    5
    Dermal cyst
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Decubitus ulcer
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Angioedema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis acneiform
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    1
    Dry skin
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Psoriasis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    2 / 18 (11.11%)
         occurrences all number
    1
    2
    3
    Papule
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Pain of skin
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Night sweats
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Erythema
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Rash
         subjects affected / exposed
    4 / 22 (18.18%)
    2 / 22 (9.09%)
    2 / 18 (11.11%)
         occurrences all number
    5
    2
    2
    Skin exfoliation
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Skin fissures
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Renal cyst
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Hypothyroidism
         subjects affected / exposed
    3 / 22 (13.64%)
    4 / 22 (18.18%)
    1 / 18 (5.56%)
         occurrences all number
    3
    4
    1
    Thyroid mass
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Thyroiditis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    1
    3
    0
    Osteoporotic fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 22 (13.64%)
    2 / 18 (11.11%)
         occurrences all number
    3
    5
    2
    Back pain
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    3 / 18 (16.67%)
         occurrences all number
    1
    4
    3
    Pain in extremity
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Infections and infestations
    Body tinea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 22 (0.00%)
    4 / 22 (18.18%)
    2 / 18 (11.11%)
         occurrences all number
    0
    4
    2
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Folliculitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    External ear cellulitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    2
    4
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
    4 / 18 (22.22%)
         occurrences all number
    2
    1
    5
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 22 (13.64%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    Sinusitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Suspected COVID-19
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    4 / 18 (22.22%)
         occurrences all number
    1
    2
    5
    Urinary tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    2
    Metabolism and nutrition disorders
    Folate deficiency
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Dehydration
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    2
    0
    1
    Decreased appetite
         subjects affected / exposed
    7 / 22 (31.82%)
    7 / 22 (31.82%)
    5 / 18 (27.78%)
         occurrences all number
    8
    9
    7
    Glucose tolerance impaired
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    1
    1
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    2
    3
    5
    Hyperphosphataemia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    Hypermagnesaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    5 / 22 (22.73%)
    4 / 22 (18.18%)
    1 / 18 (5.56%)
         occurrences all number
    14
    8
    1
    Hypochloraemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 22 (18.18%)
    3 / 18 (16.67%)
         occurrences all number
    1
    5
    3
    Hypomagnesaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 22 (13.64%)
    1 / 18 (5.56%)
         occurrences all number
    4
    3
    1
    Hypoalbuminaemia
         subjects affected / exposed
    5 / 22 (22.73%)
    7 / 22 (31.82%)
    6 / 18 (33.33%)
         occurrences all number
    6
    11
    9
    Hyperuricaemia
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 22 (13.64%)
    4 / 18 (22.22%)
         occurrences all number
    7
    8
    6
    Hyponatraemia
         subjects affected / exposed
    5 / 22 (22.73%)
    6 / 22 (27.27%)
    5 / 18 (27.78%)
         occurrences all number
    6
    11
    13
    Hypophosphataemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoproteinaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences all number
    1
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Apr 2021
    Protocol Amendment 1.0
    21 Apr 2022
    Protocol Amendment 2.0

    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.
    Since no participants were enrolled under PA 2, no analyses of the primary or secondary endpoints were conducted. Participants enrolled under PA 1 were excluded from the primary and secondary analyses outlined for PA 2.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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