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    Clinical Trial Results:
    A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-2)

    Summary
    EudraCT number
    		 2017-004288-11
    Trial protocol
    		 GB   IT  
    Global end of trial date
    09 Aug 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Aug 2023
    First version publication date
    19 Aug 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ADCT-402-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03589469
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ADC Therapeutics SA
    Sponsor organisation address
    Route de la Corniche, 3B, Epalinges, Switzerland, 1066
    Public contact
    Clinical Trials Information, ADC Therapeutics SA, clinicaltrials@adctherapeutics.com
    Scientific contact
    Clinical Trials Information, ADC Therapeutics SA, clinicaltrials@adctherapeutics.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Sep 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate the efficacy of single agent loncastuximab tesirine in participants with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).
    Protection of trial subjects
    This study was conducted in compliance with the Declaration of Helsinki and with Good Clinical Practices.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 31
    Country: Number of subjects enrolled
    Italy: 53
    Country: Number of subjects enrolled
    United States: 59
    Country: Number of subjects enrolled
    Switzerland: 2
    Worldwide total number of subjects
    145
    EEA total number of subjects
    53
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    65
    From 65 to 84 years
    78
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were enrolled at 28 study sites in Italy, Switzerland, the United Kingdom, and the United States from 01 August 2018 to 09 August 2022.

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

    Arms
    Arm title
    		 Loncastuximab Tesirine
    Arm description
    		 Participants received loncastuximab tesirine as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg once every 3 weeks (Q3W) for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Loncastuximab tesirine
    Investigational medicinal product code
    ADCT-402
    Other name
    Zynlonta
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    intravenous infusion

    Number of subjects in period 1
    		Loncastuximab Tesirine
    Started
    145
    Completed
    11
    Not completed
    134
         Physician decision
    20
         Consent withdrawn by subject
    8
         Death
    97
         Miscellaneous
    1
         Lost to follow-up
    8

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Loncastuximab Tesirine
    Reporting group description
    		 Participants received loncastuximab tesirine as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg once every 3 weeks (Q3W) for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.

    Reporting group values
    		 Loncastuximab Tesirine Total
    Number of subjects
    		 145 145
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.7 ( 13.63 ) -
    Gender categorical
    Units: Subjects
        Female
    		 60 60
        Male
    		 85 85
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 13 13
        Not Hispanic or Latino
    		 132 132
        Unknown or Not Reported
    		 0 0
    Race
    Units: Subjects
        White
    		 130 130
        Black or African American
    		 5 5
        Asian
    		 3 3
        American Indian or Alaskan Native
    		 1 1
        Native Hawaiian or Pacific Islander
    		 1 1
        Other
    		 5 5

    End points

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    End points reporting groups
    Reporting group title
    Loncastuximab Tesirine
    Reporting group description
    		 Participants received loncastuximab tesirine as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg once every 3 weeks (Q3W) for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.

    Primary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR) [1]
    End point description
    ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Primary
    End point timeframe
    Up to 21.5 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No additional statistical analyses were pre-specified for this endpoint.
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: percentage of participants
        number (confidence interval 95%)
    48.3 (39.9 to 56.7)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR defined as the time from the first documentation of tumor response to disease progression or death. Participants in the all-treated population who achieved a CR or PR. Values of "99999" indicate the upper confidence interval could not be calculated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to 39 months
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    70
    Units: months
        median (confidence interval 95%)
    13.37 (6.87 to 99999)
    No statistical analyses for this end point

    Secondary: Relapse-free Survival (RFS)

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    End point title
    		 Relapse-free Survival (RFS)
    End point description
    RFS was defined as the time from the documentation of CR to disease progression or death. Participants in the all-treated population who achieved CR. Values of "99999" indicate the median, lower and upper confidence interval could not be calculated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to 39 months
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    36
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Complete Response (CR) Rate

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    End point title
    		 Complete Response (CR) Rate
    End point description
    CR rate defined as the percentage of treated participants with a BOR of CR. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Up to 39 months
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: percentage of participants
        number (confidence interval 95%)
    24.8 (18.0 to 32.7)
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS)

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    End point title
    		 Progression-free Survival (PFS)
    End point description
    PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Up to 40 months
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: months
        median (confidence interval 95%)
    4.93 (2.89 to 8.31)
    No statistical analyses for this end point

    Secondary: Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with treatment. A TEAE was an adverse event with an onset that began or worsened on or after the first dose date and until 30 days after the last dose date, or start of a new anticancer therapy/procedure, whichever came earlier. TEAE assessments also included those per the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥3 AEs and serious TEAEs. AEs were graded using CTCAE version 4 and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. For events not listed in the CTCAE criteria, the same grading was used. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Up to 599 days
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: participants
        Any TEAE
    143
        Grade ≥3 TEAE
    107
        Serious TEAE
    57
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time between the start of treatment and death from any cause. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Up to 43 months
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: months
        median (confidence interval 95%)
    9.53 (6.74 to 11.47)
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

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    End point title
    		 Number of Participants With Clinically Significant Change From Baseline in Vital Signs
    End point description
    Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to 599 days
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: participants
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests

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    End point title
    		 Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
    End point description
    Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to 599 days
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: participants
    83
    No statistical analyses for this end point

    Secondary: Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment

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    End point title
    		 Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
    End point description
    ECOG (Eastern Cooperative Oncology Group) Performance Status is scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores include the following: • 0 = fully active, able to carry on all pre-disease performance without restriction • 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work • 2 = ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours • 3 = capable of only limited self-care; confined to bed or chair more than 50% of waking hours • 4 = completely disabled; cannot carry on any self-care; totally confined to bed or chair • 5 = dead. All-treated population - all participants who received at least 1 dose of treatment. Results are presented for participants with data available for analysis at end of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and end of treatment (up to 599 days)
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145 [2]
    Units: participants
        Baseline: ECOG score 0
    58
        Baseline: ECOG score 1
    78
        Baseline: ECOG score 2
    9
        Baseline: ECOG score 3
    0
        Baseline: ECOG score 4
    0
        Baseline: ECOG score 5
    0
        End of treatment: ECOG score 0
    44
        End of treatment: ECOG score 1
    50
        End of treatment: ECOG score 2
    14
        End of treatment: ECOG score 3
    2
        End of treatment: ECOG score 4
    1
        End of treatment: ECOG score 5
    0
    Notes
    [2] - Baseline n = 145; End of treatment n = 111.
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)

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    End point title
    		 Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)
    End point description
    Clinically significant changes from baseline for 12-lead ECGs were measured as abnormal QT interval corrected by Fridericia formula (QTcF) and QT interval corrected by Bazett formula (QTcB) values. All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to 599 days
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: participants
        QTcB maximum change from baseline: >30, <=60 msec
    30
        QTcB maximum change from baseline: >60 msec
    4
        QTcF maximum change from baseline: >30, <=60 msec
    23
        QTcF maximum change from baseline: >60 msec
    1
    No statistical analyses for this end point

    Secondary: Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    Pharmacokinetic (PK) population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion.
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    142
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 142)
    2430 ( 38.8 )
        Conjugated Antibody Cycle 2 (n = 117)
    2734 ( 35.8 )
        Conjugated Antibody Cycle 3 (n = 83)
    1694 ( 47.6 )
        Total Antibody Cycle 1 (n = 142)
    3267 ( 36.7 )
        Total Antibody Cycle 2 (n = 117)
    3756 ( 31.3 )
        Total Antibody Cycle 3 (n = 81)
    2581 ( 41.9 )
        SG3199 Cycle 1 (n = 8)
    0.0410 ( 56.6 )
        SG3199 Cycle 2 (n = 5)
    0.0490 ( 78.8 )
        SG3199 Cycle 3 (n = 3)
    0.0320 ( 20.3 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    143
    Units: day*ng/mL
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 143)
    15850 ( 105 )
        Conjugated Antibody Cycle 2 (n = 116)
    23913 ( 67.1 )
        Conjugated Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 1 (n = 143)
    22160 ( 106 )
        Total Antibody Cycle 2 (n = 116)
    33762 ( 67.2 )
        Total Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 1 (n = 8)
    0.00400 ( 576 )
        SG3199 Cycle 2 (n = 5)
    0.00100 ( 204 )
        SG3199 Cycle 3 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    99
    Units: day*ng/mL
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 32)
    19825 ( 52.9 )
        Conjugated Antibody Cycle 2 (n = 99)
    26902 ( 33.4 )
        Conjugated Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 1 (n = 27)
    25778 ( 61.3 )
        Total Antibody Cycle 2 (n = 97)
    37761 ( 30.4 )
        Total Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 1 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 2 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 3 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    90
    Units: days
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 32)
    8.85 ( 53.5 )
        Conjugated Antibody Cycle 2 (n = 90)
    15.2 ( 31.7 )
        Conjugated Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 1 (n = 27)
    8.66 ( 54.6 )
        Total Antibody Cycle 2 (n = 63)
    20.9 ( 56.5 )
        Total Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 1 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 2 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 3 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    99
    Units: L/day
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 32)
    0.458 ( 47.6 )
        Conjugated Antibody Cycle 2 (n = 99)
    0.331 ( 32.0 )
        Total Antibody Cycle 1 (n = 27)
    0.418 ( 56.5 )
        Total Antibody Cycle 2 (n = 97)
    0.285 ( 31.3 )
        SG3199 Cycle 1 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 2 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre-Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    90
    Units: liters
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 32)
    4.24 ( 39.6 )
        Conjugated Antibody Cycle 2 (n = 90)
    6.40 ( 36.5 )
        Conjugated Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 1 (n = 27)
    4.10 ( 36.4 )
        Total Antibody Cycle 2 (n = 63)
    7.54 ( 58.9 )
        Total Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 1 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 2 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 3 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199

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    End point title
    		 Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
    End point description
    AI is the ratio of AUC0-last for each cycle divided by AUC0-last of the previous cycle. PK population: All participants in the per-protocol population (all participants in the all-treated population without major protocol deviations) with at least 1 pre- Cycle 1 Day 1 and 1 post-dose valid assessment. Only participants with data available for analysis are presented. Values of "99999" indicate n = 0.
    End point type
    Secondary
    End point timeframe
    Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    90
    Units: ratio
    geometric mean (geometric coefficient of variation)
        Conjugated Antibody Cycle 1 (n = 0)
    99999 ( 99999 )
        Conjugated Antibody Cycle 2 (n = 90)
    1.65 ( 18.5 )
        Conjugated Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 1 (n = 0)
    99999 ( 99999 )
        Total Antibody Cycle 2 (n = 63)
    2.07 ( 38.1 )
        Total Antibody Cycle 3 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 1 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 2 (n = 0)
    99999 ( 99999 )
        SG3199 Cycle 3 (n = 0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine

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    End point title
    		 Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
    End point description
    All-treated population - all participants who received at least 1 dose of treatment.
    End point type
    Secondary
    End point timeframe
    Up to 599 days
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    145
    Units: participants
        Confirmed Positive ADA Pre-dose
    1
        Confirmed Positive ADA Post-dose Only
    0
        Confirmed Positive ADA Anytime
    1
    No statistical analyses for this end point

    Secondary: Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)

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    End point title
    		 Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
    End point description
    EQ-5D-5L is designed as an international, standardized, instrument for describing and evaluating quality of life (QoL). In the EQ-5D-5L VAS participants are asked to indicate their health state today on a VAS with the endpoints labeled ‘the best health you can imagine’ (score 100) and ‘the worst health you can imagine’ (score 0). A higher score on the VAS indicates better health related QoL. A positive change from baseline indicates an improvement in health related QoL. Patient reported outcome (PRO) population. Only participants with data available for analysis are included. Number of subjects analysed represents all participants who contributed data to this assessment, though not all participants contributed data to each time point. Values of "99999" indicate standard deviation could not be calculated as n = 1.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    130
    Units: score on a scale
    arithmetic mean (standard deviation)
        Cycle 2 Day 1 (n = 108)
    -0.1 ( 15.97 )
        Cycle 3 Day 1 (n = 76)
    1.3 ( 16.85 )
        Cycle 4 Day 1 (n = 58)
    2.8 ( 15.00 )
        Cycle 5 Day 1 (n = 44)
    2.8 ( 13.50 )
        Cycle 6 Day 1 (n = 33)
    3.0 ( 17.45 )
        Cycle 7 Day 1 (n = 28)
    4.0 ( 12.91 )
        Cycle 8 Day 1 (n = 22)
    7.3 ( 12.87 )
        Cycle 9 Day 1 (n = 20)
    7.7 ( 15.69 )
        Cycle 10 Day 1 (n = 13)
    12.2 ( 15.64 )
        Cycle 11 Day 1 (n = 12)
    11.8 ( 17.62 )
        Cycle 12 Day 1 (n = 10)
    16.3 ( 16.06 )
        Cycle 13 Day 1 (n = 8)
    6.0 ( 16.54 )
        Cycle 14 Day 1 (n = 6)
    12.2 ( 15.43 )
        Cycle 15 Day 1 (n = 5)
    6.6 ( 12.36 )
        Cycle 16 Day 1 (n = 4)
    5.5 ( 13.70 )
        Cycle 17 Day 1 (n = 4)
    8.3 ( 13.62 )
        Cycle 18 Day 1 (n = 3)
    11.0 ( 11.53 )
        Cycle 19 Day 1 (n = 2)
    11.5 ( 16.26 )
        Cycle 20 Day 1 (n = 1)
    23.0 ( 99999 )
        Cycle 21 Day 1 (n = 2)
    16.5 ( 9.19 )
        Cycle 22 Day 1 (n = 2)
    16.5 ( 9.19 )
        Cycle 23 Day 1 (n = 1)
    23.0 ( 99999 )
        Cycle 24 Day 1 (n = 1)
    23.0 ( 99999 )
        Cycle 25 Day 1 (n = 1)
    23.0 ( 99999 )
        Cycle 26 Day 1 (n = 1)
    23.0 ( 99999 )
        End of treatment (n = 98)
    -8.3 ( 19.85 )
    No statistical analyses for this end point

    Secondary: Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)

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    End point title
    		 Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)
    End point description
    Composed of the Functional Assessment of Cancer Therapy - General (FACT-G) plus the 15-item LymS. The FACTG questionnaire contains 27 items covering 4 core health related quality of life (QoL) subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The LymS addresses issues including pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. Score range for the LymS was 0 - 60, where a higher score indicates less symptoms. The LymS score is reported. A positive change from baseline indicates an improvement in health related QoL. PRO population. Only participants with data available for analysis are included. Number of subjects analysed represents all participants who contributed data to this assessment, though not all participants contributed data to each time point. Values of "9999" indicate n = 0; "99999" indicate standard deviation could not be calculated as n = 1.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
    End point values
    		 Loncastuximab Tesirine
    Number of subjects analysed
    130
    Units: score on a scale
    arithmetic mean (standard deviation)
        Cycle 2 Day 1 (n = 110)
    0.95 ( 7.114 )
        Cycle 3 Day 1 (n = 78)
    1.34 ( 8.764 )
        Cycle 4 Day 1 (n = 60)
    2.09 ( 8.832 )
        Cycle 5 Day 1 (n = 47)
    0.16 ( 8.506 )
        Cycle 6 Day 1 (n = 33)
    1.16 ( 9.918 )
        Cycle 7 Day 1 (n = 29)
    1.00 ( 11.474 )
        Cycle 8 Day 1 (n = 22)
    3.43 ( 10.141 )
        Cycle 9 Day 1 (n = 20)
    2.17 ( 9.498 )
        Cycle 10 Day 1 (n = 13)
    3.18 ( 11.769 )
        Cycle 11 Day 1 (n = 12)
    4.35 ( 13.053 )
        Cycle 12 Day 1 (n = 10)
    4.90 ( 11.140 )
        Cycle 13 Day 1 (n = 9)
    2.01 ( 16.871 )
        Cycle 14 Day 1 (n = 6)
    0.63 ( 17.442 )
        Cycle 15 Day 1 (n = 5)
    -3.27 ( 7.691 )
        Cycle 16 Day 1 (n = 4)
    -8.04 ( 10.561 )
        Cycle 17 Day 1 (n = 4)
    -6.88 ( 9.360 )
        Cycle 18 Day 1 (n = 3)
    -5.00 ( 7.937 )
        Cycle 19 Day 1 (n = 2)
    -1.00 ( 4.243 )
        Cycle 20 Day 1 (n = 2)
    -2.25 ( 4.596 )
        Cycle 21 Day 1 (n = 2)
    -0.50 ( 2.121 )
        Cycle 22 Day 1 (n = 2)
    -1.00 ( 2.828 )
        Cycle 23 Day 1 (n = 1)
    1.00 ( 99999 )
        Cycle 24 Day 1 (n = 0)
    9999 ( 9999 )
        Cycle 25 Day 1 (n = 1)
    1.00 ( 99999 )
        End of treatment (n = 98)
    -1.19 ( 9.042 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 43 months
    Adverse event reporting additional description
    All non-serious AEs at a frequency threshold of >=5% and all SAEs, regardless of relationship to study drug, were collected from the time the participant signs the ICF until 30 days after the last dose of study drug or start of new anti-cancer therapy, whichever is earlier; thereafter, only related SAEs were collected, with two exceptions.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Loncastuximab Tesirine
    Reporting group description
    		 Participants received loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg once Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.

    Serious adverse events
    		 Loncastuximab Tesirine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    57 / 145 (39.31%)
         number of deaths (all causes)
    97
         number of deaths resulting from adverse events
    8
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Diffuse large B-cell lymphoma
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Vascular disorders
    Thrombosis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematoma
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Embolism
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Disease progression
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Face oedema
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 145 (2.76%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oedema peripheral
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Non-cardiac chest pain
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pneumonitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleuritic pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 145 (2.07%)
         occurrences causally related to treatment / all
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Confusional state
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intentional self-injury
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mental status changes
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Fall
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative hypotension
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Pericarditis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pericardial effusion
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Psychomotor skills impaired
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Facial nerve disorder
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Febrile neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 145 (3.45%)
         occurrences causally related to treatment / all
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    Anaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Small intestinal obstruction
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysphagia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ascites
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 145 (2.07%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Small intestinal perforation
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Renal and urinary disorders
    Acute kidney injury
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Hydronephrosis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ureterolithiasis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck pain
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Sepsis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Rhinovirus infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia fungal
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    Metapneumovirus infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Klebsiella infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Urinary tract infection bacterial
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Soft tissue infection
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypercalcaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 145 (4.14%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    Dehydration
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Loncastuximab Tesirine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    139 / 145 (95.86%)
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    29 / 145 (20.00%)
         occurrences all number
    35
    Aspartate aminotransferase increased
         subjects affected / exposed
    23 / 145 (15.86%)
         occurrences all number
    36
    Alanine aminotransferase increased
         subjects affected / exposed
    22 / 145 (15.17%)
         occurrences all number
    27
    Weight increased
         subjects affected / exposed
    10 / 145 (6.90%)
         occurrences all number
    11
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    61 / 145 (42.07%)
         occurrences all number
    74
    Vascular disorders
    Hypotension
         subjects affected / exposed
    10 / 145 (6.90%)
         occurrences all number
    12
    Hypertension
         subjects affected / exposed
    8 / 145 (5.52%)
         occurrences all number
    12
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    11 / 145 (7.59%)
         occurrences all number
    12
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 145 (6.21%)
         occurrences all number
    9
    Headache
         subjects affected / exposed
    15 / 145 (10.34%)
         occurrences all number
    20
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    11 / 145 (7.59%)
         occurrences all number
    18
    Leukopenia
         subjects affected / exposed
    21 / 145 (14.48%)
         occurrences all number
    34
    Anaemia
         subjects affected / exposed
    38 / 145 (26.21%)
         occurrences all number
    54
    Thrombocytopenia
         subjects affected / exposed
    48 / 145 (33.10%)
         occurrences all number
    73
    Neutropenia
         subjects affected / exposed
    58 / 145 (40.00%)
         occurrences all number
    100
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    14 / 145 (9.66%)
         occurrences all number
    16
    Pyrexia
         subjects affected / exposed
    25 / 145 (17.24%)
         occurrences all number
    38
    Oedema peripheral
         subjects affected / exposed
    28 / 145 (19.31%)
         occurrences all number
    33
    Fatigue
         subjects affected / exposed
    40 / 145 (27.59%)
         occurrences all number
    44
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    25 / 145 (17.24%)
         occurrences all number
    34
    Nausea
         subjects affected / exposed
    34 / 145 (23.45%)
         occurrences all number
    42
    Abdominal pain
         subjects affected / exposed
    16 / 145 (11.03%)
         occurrences all number
    18
    Constipation
         subjects affected / exposed
    17 / 145 (11.72%)
         occurrences all number
    17
    Vomiting
         subjects affected / exposed
    19 / 145 (13.10%)
         occurrences all number
    22
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    14 / 145 (9.66%)
         occurrences all number
    15
    Dyspnoea
         subjects affected / exposed
    17 / 145 (11.72%)
         occurrences all number
    17
    Cough
         subjects affected / exposed
    32 / 145 (22.07%)
         occurrences all number
    33
    Nasal congestion
         subjects affected / exposed
    8 / 145 (5.52%)
         occurrences all number
    8
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    8 / 145 (5.52%)
         occurrences all number
    8
    Photosensitivity reaction
         subjects affected / exposed
    15 / 145 (10.34%)
         occurrences all number
    18
    Erythema
         subjects affected / exposed
    15 / 145 (10.34%)
         occurrences all number
    27
    Rash
         subjects affected / exposed
    19 / 145 (13.10%)
         occurrences all number
    20
    Pruritus
         subjects affected / exposed
    19 / 145 (13.10%)
         occurrences all number
    20
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    16 / 145 (11.03%)
         occurrences all number
    16
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    8 / 145 (5.52%)
         occurrences all number
    8
    Back pain
         subjects affected / exposed
    9 / 145 (6.21%)
         occurrences all number
    9
    Pain in extremity
         subjects affected / exposed
    9 / 145 (6.21%)
         occurrences all number
    9
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    23 / 145 (15.86%)
         occurrences all number
    30
    Hypophosphataemia
         subjects affected / exposed
    23 / 145 (15.86%)
         occurrences all number
    33
    Decreased appetite
         subjects affected / exposed
    22 / 145 (15.17%)
         occurrences all number
    22
    Hypomagnesaemia
         subjects affected / exposed
    20 / 145 (13.79%)
         occurrences all number
    23
    Hypocalcaemia
         subjects affected / exposed
    12 / 145 (8.28%)
         occurrences all number
    16
    Hyperglycaemia
         subjects affected / exposed
    11 / 145 (7.59%)
         occurrences all number
    14
    Hyponatraemia
         subjects affected / exposed
    9 / 145 (6.21%)
         occurrences all number
    10

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Apr 2018
    The original protocol was finalized on 09 Mar 2018 and was amended before implementation in response to United States Food and Drug Administration recommendations. The purposes of the amendment were the following: - The study design was changed to a single cohort with the primary endpoint being ORR in all-treated participants, resulting in changes to primary and secondary objectives and endpoints, and statistical considerations. - For eligibility, pathologic diagnosis was clarified to align with the 2016 World Health Organization classification, the requirement for participants to be ineligible or have failed stem cell transplant (SCT) was removed (as the Agency felt that loncastuximab tesirine was potentially suitable for third line therapy in participants who were potentially eligible for SCT), and the specific requirement for rituximab therapy was deleted as it was expected that all participants would have received this in at least 1 prior line of therapy. - For participants whose disease was not positron-emission tomography (PET)-avid, bone marrow biopsy was added as part of baseline staging and disease assessment if clinically appropriate to fully align with the 2014 Lugano Classification. - Safety follow-up was extended to 180 days after transplant for participants who had responded to loncastuximab tesirine and gone on to SCT to monitor for possible increased transplant-related toxicity in participants who had been treated with loncastuximab tesirine.
    24 Sep 2018
    The purposes of the amendment were the following: - Participants with bulky disease (defined as at least 1 lymph node ≥ 10 cm in longest diameter) were excluded based on analysis of Phase 1 data showing that these participants had an ORR of 11%. Based on an interim analysis this was the ORR at the time of this analysis. - The inclusion criterion regarding hepatic function was revised to no longer allow participants with alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase ≤ 5 × upper limit of normal if there was liver involvement, to be consistent with the requirement to hold the dose of loncastuximab tesirine for participants with Grade ≥ 2 liver function test abnormalities as specified in Section 9.4.5.1.2. - Participants who were clinically benefiting were allowed to continue treatment beyond 1 year with Sponsor review and approval. - A requirement for dose discontinuation for dose delays > 5 weeks due to toxicity at least possibly related to loncastuximab tesirine was added. - The requirement for IV contrast for PET-computer tomography (CT) was removed and the type and timing of efficacy assessments were clarified.
    09 Jul 2019
    The purposes of the amendment were the following: - The text was updated to include information regarding monitoring for extravasation during or after loncastuximab tesirine infusion because of updated safety information. - Efficacy assessments were updated to allow for capture of response information during the follow-up period for participants who received chimeric antigen receptor T-cell (CAR-T) therapy after loncastuximab tesirine treatment. - AE/serious AE reporting requirements for participants who received CAR-T therapy after loncastuximab tesirine discontinuation were added.

    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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