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    Clinical Trial Results:
    Risk-based, response-adapted, Phase II open-label trial of nivolumab + brentuximab vedotin (N+ Bv) for children, adolescents, and young adults with relapsed/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL) after failure of first-line therapy, followed by brentuximab + bendamustine (Bv + B) for participants with a suboptimal response. CheckMate 744: CHECKpoint pathway and nivolumab clinical Trial Evaluation

    Summary
    EudraCT number
    2016-002347-41
    Trial protocol
    CZ   ES   IE   DE   GB   NL   PL   Outside EU/EEA   IT  
    Global end of trial date
    28 May 2024

    Results information
    Results version number
    v1(current)
    This version publication date
    17 Nov 2024
    First version publication date
    17 Nov 2024
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-744
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02927769
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001407-PIP02-15
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 May 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To describe the complete metabolic response (CMR) rate before radiation therapy/high-dose chemotherapy/autologous stem-cell transplant and event-free survival (EFS) rate at 3 years, as assessed by blinded independent central review (BICR), using Lugano 2014 response criteria.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Netherlands: 6
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 20
    Worldwide total number of subjects
    72
    EEA total number of subjects
    48
    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)
    7
    Adolescents (12-17 years)
    42
    Adults (18-64 years)
    23
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    All participants entered the Induction phase. Participants entered the Intensification phase if they received brentuximab + bendamustine (Bv + B). Participants entered the Consolidation Phase if they received radiation therapy (C1) or high-dose chemotherapy/autologous stem cell transplant (HDCT/ASCT) (C2).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.
    Arm type
    Experimental

    Investigational medicinal product name
    Brentuximab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.8 mg/kg every 21 days

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    BMS-936558
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 21 days

    Arm title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    BMS-936558
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 21 days

    Number of subjects in period 1
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Started
    28
    44
    Completed
    27
    42
    Not completed
    1
    2
         Disease progression
    -
    1
         Study drug toxicity
    1
    1
    Period 2
    Period 2 title
    Consolidation Phase
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    BMS-936558
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 21 days

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Investigational medicinal product name
    Brentuximab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.8 mg/kg every 21 days

    Arm title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    BMS-936558
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 21 days

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Number of subjects in period 2 [1]
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Started
    22
    32
    Completed
    22
    32
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all participants who started in the induction phase entered the intensification or consolidation phase.
    Period 3
    Period 3 title
    Intensification Phase
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.
    Arm type
    Experimental

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Investigational medicinal product name
    Brentuximab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.8 mg/kg every 21 days

    Arm title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Arm description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    90 mg/m2/day, 21-day cycles (on Days1 and 2)

    Investigational medicinal product name
    Brentuximab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.8 mg/kg every 21 days

    Number of subjects in period 3 [2]
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Started
    6
    11
    Completed
    5
    11
    Not completed
    1
    0
         Study drug toxicity
    1
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all participants who started in the induction phase entered the intensification or consolidation phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.

    Reporting group title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.

    Reporting group values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse Total
    Number of subjects
    28 44 72
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    3 4 7
        Adolescents (12-17 years)
    15 27 42
        Adults (18-64 years)
    10 13 23
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    17.0 ( 4.3 ) 16.2 ( 3.7 ) -
    Sex: Female, Male
    Units: Participants
        Female
    18 15 33
        Male
    10 29 39
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    1 0 1
        Native Hawaiian or Other Pacific Islander
    0 1 1
        Black or African American
    1 1 2
        White
    25 41 66
        More than one race
    0 0 0
        Unknown or Not Reported
    1 1 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    3 1 4
        Not Hispanic or Latino
    8 20 28
        Unknown or Not Reported
    17 23 40

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.

    Reporting group title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.
    Reporting group title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.

    Reporting group title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.
    Reporting group title
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up.

    Reporting group title
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment.

    Primary: Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1

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    End point title
    Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1 [1] [2]
    End point description
    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
    End point type
    Primary
    End point timeframe
    From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
    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: Only descriptive statistics were planned for this endpoint.
    [2] - 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: Prespecified to be collected for Cohort 1 only.
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Number of subjects analysed
    28
    Units: Percent of participants
        number (confidence interval 90%)
    92.9 (79.2 to 98.7)
    No statistical analyses for this end point

    Primary: Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1

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    End point title
    Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1 [3] [4]
    End point description
    Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death . PD : Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease CM): Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No Bone marrow: No FDG-avid disease Participants without an “event” were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior “event” were censored at the last tumor assessment prior to or upon starting subsequent therapy. Based on Kaplan-Meier Estimates.
    End point type
    Primary
    End point timeframe
    At 3 years post first dose of study therapy
    Notes
    [3] - 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: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be collected for Cohort 1 only.
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Number of subjects analysed
    28
    Units: Percent of participants
        number (confidence interval 90%)
    87.5 (70.6 to 95.0)
    No statistical analyses for this end point

    Primary: Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2

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    End point title
    Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2 [5] [6]
    End point description
    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
    End point type
    Primary
    End point timeframe
    From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
    Notes
    [5] - 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: Only descriptive statistics were planned for this endpoint.
    [6] - 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: Prespecified to be collected for Cohort 1 only.
    End point values
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    44
    Units: Percent of participants
        number (confidence interval 90%)
    88.6 (77.6 to 95.4)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)

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    End point title
    Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)
    End point description
    Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved a best response of complete metabolic response (CMR) or partial metabolic response (PMR). Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Partial metabolic response (PMR): • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline • New lesions: None • Bone marrow: Residual uptake higher than normal, reduced from baseline. Participants who came off early for toxicity without CMR or PMR were evaluable.
    End point type
    Secondary
    End point timeframe
    From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Percent of participants
        number (confidence interval 90%)
    96.4 (84.1 to 99.8)
    93.2 (83.3 to 98.1)
    No statistical analyses for this end point

    Secondary: Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1

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    End point title
    Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1 [7]
    End point description
    Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death . PD : Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease CMR: Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an “event” were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior “event” were censored at the last tumor assessment prior to or upon starting subsequent therapy. Based on Kaplan-Meier Estimates.
    End point type
    Secondary
    End point timeframe
    At 3 years post first dose of study therapy
    Notes
    [7] - 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: Prespecified to be collected for Cohort 1 only.
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Number of subjects analysed
    28
    Units: Percent of participants
        number (confidence interval 90%)
    88.5 (72.8 to 95.4)
    No statistical analyses for this end point

    Secondary: Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1

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    End point title
    Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1 [8]
    End point description
    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Participants who come off early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
    End point type
    Secondary
    End point timeframe
    From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
    Notes
    [8] - 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: Prespecified to be collected for Cohort 1 only.
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
    Number of subjects analysed
    28
    Units: Percent of participants
        number (confidence interval 90%)
    89.3 (74.6 to 97.0)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)

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    End point title
    Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
    End point description
    Duration of response (DOR) is from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment. Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to starting subsequent anticancer therapy. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Partial metabolic response: • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline • New lesions: None • Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates. "99999 = N/A".
    End point type
    Secondary
    End point timeframe
    From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    26
    39
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)

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    End point title
    Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)
    End point description
    Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by BICR or death. Progressive Disease (PD): Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Based on Kaplan-Meier Estimates.
    End point type
    Secondary
    End point timeframe
    At 3 years post first dose of study therapy
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Percent of participants
        number (confidence interval 90%)
    95.2 (77.7 to 99.1)
    91.1 (78.4 to 96.5)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) Rate at 3 Years by Investigator

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    End point title
    Progression Free Survival (PFS) Rate at 3 Years by Investigator
    End point description
    Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by investigator or death. Progressive Disease (PD): Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Based on Kaplan-Meier Estimates.
    End point type
    Secondary
    End point timeframe
    At 3 years post first dose
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Percent of participants
        number (confidence interval 90%)
    95.8 (80.2 to 99.2)
    88.1 (74.8 to 94.6)
    No statistical analyses for this end point

    Secondary: Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2

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    End point title
    Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2 [9]
    End point description
    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method.
    End point type
    Secondary
    End point timeframe
    From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
    Notes
    [9] - 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: Prespecified to be collected for Cohort 2 only.
    End point values
    Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    44
    Units: Percent of participants
        number (confidence interval 95%)
    86.4 (74.8 to 93.9)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator

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    End point title
    Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator
    End point description
    Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieve a best response of complete metabolic response (CMR) or partial metabolic response (PMR). Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Partial metabolic response: • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline • New lesions: None • Bone marrow: Residual uptake higher than normal, reduced from baseline Participants who came off early for toxicity without CMR or PMR were evaluable.
    End point type
    Secondary
    End point timeframe
    From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Percent of participants
        number (confidence interval 90%)
    100.0 (89.9 to 100.0)
    90.9 (80.4 to 96.8)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by Investigator

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    End point title
    Duration of Response (DOR) by Investigator
    End point description
    Duration of response (DOR) is from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment. Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment before starting subsequent anticancer therapy. Complete metabolic response (CMR): • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Partial metabolic response: • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline • New lesions: None • Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates. "99999=N/A".
    End point type
    Secondary
    End point timeframe
    From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: The Number of Participants with Adverse Events (AEs)

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    End point title
    The Number of Participants with Adverse Events (AEs)
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Participants
    26
    42
    No statistical analyses for this end point

    Secondary: The Number of Participants with Serious Adverse Events (SAEs)

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    End point title
    The Number of Participants with Serious Adverse Events (SAEs)
    End point description
    A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: - Results in death - Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) - Requires inpatient hospitalization or causes prolongation of existing hospitalization - Results in persistent or significant disability/incapacity - Is a congenital anomaly/birth defect - Is an important medical event.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Participants
    8
    9
    No statistical analyses for this end point

    Secondary: The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests

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    End point title
    The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests
    End point description
    The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Participants
        TSH > ULN
    6
    8
        TSH > ULN WITH TSH <= ULN AT BASELINE
    5
    4
        TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
    1
    0
        TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN
    4
    5
        TSH > ULN WITH FT3/FT4 TEST MISSING
    1
    3
        TSH < LLN
    4
    1
        TSH <LLN WITH TSH >= LLN AT BASELINE
    4
    1
        TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
    3
    1
        TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN
    1
    0
        TSH < LLN WITH FT3/FT4 TEST MISSING
    0
    0
    No statistical analyses for this end point

    Secondary: The Number of Participants with Abnormal Laboratory Values for Liver Tests

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    End point title
    The Number of Participants with Abnormal Laboratory Values for Liver Tests
    End point description
    The Number of Participants with Abnormal Laboratory Values for Liver Tests.
    End point type
    Secondary
    End point timeframe
    From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    28
    44
    Units: Participants
        ALT OR AST > 3XULN
    8
    5
        ALT OR AST> 5XULN
    3
    1
        ALT OR AST> 10XULN
    0
    0
        ALT OR AST > 20XULN
    0
    0
        TOTAL BILIRUBIN > 2XULN
    1
    0
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY
    0
    0
        ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN 30 DAYS
    0
    0
    No statistical analyses for this end point

    Secondary: Vital Sign Measurements

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    End point title
    Vital Sign Measurements
    End point description
    Data not collected
    End point type
    Secondary
    End point timeframe
    Data not collected
    End point values
    Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
    Number of subjects analysed
    0 [10]
    0 [11]
    Units: N/A
    Notes
    [10] - Data not collected
    [11] - Data not collected
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs and Non-serious AEs were assessed from first dose to 30 days after last dose of study therapy (assessed for an average of 4 months up until a maximum of 7 months).
    Adverse event reporting additional description
    Serious Adverse Events and Non-Serious Adverse Events represents all participants that received at least 1 dose of study medication.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Cohort 1: Nivo + Bv
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, as assessed by Investigator at Cycle 2 entered follow-up. The rest of the participants continued in the induction phase and received 2 additional cycles of N+Bv study therapy (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received an additional 2 cycles of treatment of N+Bv (for a total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase).

    Reporting group title
    Cohort 2: Nivo + Bv
    Reporting group description
    Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, as assessed by Investigator at Cycle 2 entered follow-up. The rest of the participants received 2 additional cycles of N+Bv study therapy (total 4 cycles = 12 weeks). - Participants who had complete metabolic response (CMR), by BICR, after a total of 4 cycles (12 weeks) of N+Bv proceeded with high-dose chemotherapy followed by an autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR had the option to receive up to 2 additional cycles of N+Bv if their HDCT/ASCT was postponed for any reason.

    Reporting group title
    Cohort 2: (Nivo + Bv) + (Bv + B)
    Reporting group description
    Participants started in the induction phase with nivolumab and brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with radiographic progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles, 12 weeks). Participants with complete metabolic response (CMR) after 4 cycles of N+Bv got with high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). Those with CMR could receive up to 2 additional cycles of N+Bv if HDCT/ASCT was postponed. Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab and bendamustine (Bv+B). Those with CMR after 2 cycles of Bv+B got HDCT/ASCT. Participants without CMR could receive 2 more cycles of Bv+B and, if CMR was attained, got HDCT/ASCT. Those with CMR could receive up to 2 additional cycles of Bv+B if HDCT/ASCT was postponed. Participants with radiographic progression after Cycle 4 N+Bv or no CMR after final Bv+B were taken off study treatment and entered follow-up.

    Reporting group title
    Cohort 1: (Nivo + Bv) + (Bv + B)
    Reporting group description
    Participants started in the induction phase and received nivolumab and brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with radiographic progression at Cycle 2 entered follow-up. The rest continued in the induction phase for 2 additional cycles of N+Bv (total 4 cycles, 12 weeks). Participants with a complete metabolic response (CMR) after 4 cycles of N+Bv received 2 more cycles of N+Bv (total 6 cycles, 18 weeks) followed by Radiation Therapy (RT) in the consolidation phase. Participants without a CMR after 4 cycles of N+Bv entered the intensification phase and received 2 cycles of brentuximab and bendamustine (Bv+B). Those who achieved CMR after these 2 cycles proceeded with RT consolidation. Participants with radiographic progression after Cycle 4 N+Bv or those who did not achieve CMR after 2 cycles of Bv+B were taken off study treatment and entered follow-up.

    Serious adverse events
    Cohort 1: Nivo + Bv Cohort 2: Nivo + Bv Cohort 2: (Nivo + Bv) + (Bv + B) Cohort 1: (Nivo + Bv) + (Bv + B)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 22 (27.27%)
    11 / 33 (33.33%)
    4 / 11 (36.36%)
    3 / 6 (50.00%)
         number of deaths (all causes)
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    3 / 6 (50.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 1
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthopnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary veno-occlusive disease
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood phosphorus increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular access complication
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Synovial cyst
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 1: Nivo + Bv Cohort 2: Nivo + Bv Cohort 2: (Nivo + Bv) + (Bv + B) Cohort 1: (Nivo + Bv) + (Bv + B)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 22 (81.82%)
    33 / 33 (100.00%)
    11 / 11 (100.00%)
    6 / 6 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 22 (0.00%)
    4 / 33 (12.12%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    1
    0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    4 / 22 (18.18%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    6
    1
    2
    1
    Fatigue
         subjects affected / exposed
    4 / 22 (18.18%)
    7 / 33 (21.21%)
    1 / 11 (9.09%)
    2 / 6 (33.33%)
         occurrences all number
    4
    12
    1
    7
    Oedema peripheral
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 22 (4.55%)
    10 / 33 (30.30%)
    5 / 11 (45.45%)
    0 / 6 (0.00%)
         occurrences all number
    1
    11
    6
    0
    Influenza like illness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    4
    2
    Gait disturbance
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 22 (4.55%)
    17 / 33 (51.52%)
    5 / 11 (45.45%)
    2 / 6 (33.33%)
         occurrences all number
    1
    22
    8
    2
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    6 / 33 (18.18%)
    3 / 11 (27.27%)
    2 / 6 (33.33%)
         occurrences all number
    1
    6
    3
    3
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    2
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    5 / 22 (22.73%)
    4 / 33 (12.12%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    5
    5
    1
    1
    Nasal congestion
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 33 (9.09%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Cough
         subjects affected / exposed
    2 / 22 (9.09%)
    8 / 33 (24.24%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    9
    0
    1
    Dyspnoea
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 33 (9.09%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Epistaxis
         subjects affected / exposed
    3 / 22 (13.64%)
    4 / 33 (12.12%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    3
    6
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Anxiety
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Agitation
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 22 (22.73%)
    2 / 33 (6.06%)
    3 / 11 (27.27%)
    2 / 6 (33.33%)
         occurrences all number
    6
    2
    4
    3
    Amylase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 22 (13.64%)
    3 / 33 (9.09%)
    2 / 11 (18.18%)
    2 / 6 (33.33%)
         occurrences all number
    6
    5
    3
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Body temperature increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Heart rate increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lipase decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lipase increased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 22 (0.00%)
    4 / 33 (12.12%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    2
    0
    Weight decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    1
    4
    2
    0
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    0
    2
    Radiation associated pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Post procedural complication
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    4 / 22 (18.18%)
    4 / 33 (12.12%)
    5 / 11 (45.45%)
    1 / 6 (16.67%)
         occurrences all number
    4
    4
    9
    2
    Vascular access site pruritus
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 33 (3.03%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Nervous system disorders
    Presyncope
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 33 (12.12%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    5
    1
    0
    Headache
         subjects affected / exposed
    10 / 22 (45.45%)
    6 / 33 (18.18%)
    4 / 11 (36.36%)
    2 / 6 (33.33%)
         occurrences all number
    12
    7
    7
    2
    Somnolence
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    6 / 33 (18.18%)
    3 / 11 (27.27%)
    1 / 6 (16.67%)
         occurrences all number
    1
    6
    3
    2
    Febrile neutropenia
         subjects affected / exposed
    0 / 22 (0.00%)
    5 / 33 (15.15%)
    4 / 11 (36.36%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    4
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 33 (12.12%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    1
    5
    2
    0
    Neutropenia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    2 / 11 (18.18%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    2
    1
    Leukopenia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Eye disorders
    Eye pain
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 22 (4.55%)
    7 / 33 (21.21%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    3
    7
    2
    1
    Abdominal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    9 / 33 (27.27%)
    4 / 11 (36.36%)
    0 / 6 (0.00%)
         occurrences all number
    1
    13
    7
    0
    Vomiting
         subjects affected / exposed
    2 / 22 (9.09%)
    7 / 33 (21.21%)
    6 / 11 (54.55%)
    3 / 6 (50.00%)
         occurrences all number
    2
    11
    22
    4
    Stomatitis
         subjects affected / exposed
    1 / 22 (4.55%)
    7 / 33 (21.21%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    1
    7
    1
    1
    Paraesthesia oral
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oral pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    9 / 22 (40.91%)
    19 / 33 (57.58%)
    11 / 11 (100.00%)
    3 / 6 (50.00%)
         occurrences all number
    11
    32
    22
    5
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Enterocolitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    5 / 22 (22.73%)
    13 / 33 (39.39%)
    4 / 11 (36.36%)
    1 / 6 (16.67%)
         occurrences all number
    6
    24
    8
    1
    Constipation
         subjects affected / exposed
    4 / 22 (18.18%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    5
    4
    1
    0
    Coating in mouth
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 33 (9.09%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    3
    0
    Dry skin
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    3
    1
    2
    Alopecia
         subjects affected / exposed
    3 / 22 (13.64%)
    5 / 33 (15.15%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    3
    5
    1
    1
    Acne
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pruritus
         subjects affected / exposed
    4 / 22 (18.18%)
    2 / 33 (6.06%)
    3 / 11 (27.27%)
    0 / 6 (0.00%)
         occurrences all number
    5
    2
    4
    0
    Night sweats
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Rash maculo-papular
         subjects affected / exposed
    2 / 22 (9.09%)
    6 / 33 (18.18%)
    2 / 11 (18.18%)
    1 / 6 (16.67%)
         occurrences all number
    3
    8
    4
    1
    Rash
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    4 / 11 (36.36%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    6
    0
    Purpura
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psoriasis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Haematuria
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    3 / 11 (27.27%)
    2 / 6 (33.33%)
         occurrences all number
    0
    4
    3
    2
    Back pain
         subjects affected / exposed
    1 / 22 (4.55%)
    5 / 33 (15.15%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    1
    7
    2
    0
    Bone pain
         subjects affected / exposed
    0 / 22 (0.00%)
    4 / 33 (12.12%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Flank pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Groin pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 33 (6.06%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Pain in extremity
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 33 (6.06%)
    2 / 11 (18.18%)
    2 / 6 (33.33%)
         occurrences all number
    4
    2
    2
    2
    Pain in jaw
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 33 (6.06%)
    0 / 11 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Device related infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Epstein-Barr virus infection reactivation
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Otitis media
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 33 (9.09%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 33 (9.09%)
    0 / 11 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    3
    0
    2
    Staphylococcal infection
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 33 (6.06%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    2
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 22 (0.00%)
    8 / 33 (24.24%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    0
    9
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    2
    Hypochloraemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    0 / 11 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    4
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    2 / 11 (18.18%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypouricaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 33 (0.00%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 33 (3.03%)
    1 / 11 (9.09%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2017
    Per Health Authority recommendations (eg,: Add additional Safety Assessments to provide more frequent safety monitoring for this patient population during Induction Phase, update an optional lab sample and revise Section 2 Tables-due to new Safety Labs, add futility rule for R2 Cohort, amend inclusion criteria language from Direct to Total Bilirubin, simplify nivolumab dose delay criteria language and formatting, include guidance for live vaccinations, and clarify the need to follow local guidelines for opportunistic infection prophylaxis). Additionally, clarifying: R1 Consolidation Therapy may be inclusive of all types of Radiation Therapy (RT) per institutional guidelines, adds up to 2 additional cycles of Bv+B with BMS MM approval for R2 cohort consolidation therapy delays (to be consistent with the approach taken for Induction Phase, N+Bv), deletes wording “for biomarker analysis” as the biopsy isrequired per Standard of Care and provided to BMS for histologic confirmation of disease and biomarker testing, modification of requirements for FDG-PET at screening and during treatment in alignment with Standard of Care practices, and LYRIC 2016 criteria will be added as an exploratory endpoint for future data analysis according to refinement of LUGANO classification in the era of immunomodulatory therapy.
    26 Mar 2021
    The response assessment by investigators using Lugano 2014 response criteria was added as a secondary endpoint to allow for a comprehensive interpretation of the study data. Guidance for collection and submission of tumor assessments was added to support the evaluation of this new secondary endpoint. Contraception requirements for female participants of child bearing potential were modified to properly align with Nivolumab clinical research standard guidelines and brentuximab label. Other minor edits were made, as described in the Summary of Key Changes.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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

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