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    Clinical Trial Results:
    An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY)

    Summary
    EudraCT number
    		 2015-004506-42
    Trial protocol
    		 HU   DE   ES   PL  
    Global end of trial date
    19 Oct 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    20 Nov 2019
    First version publication date
    16 Oct 2019
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Updated end point information

    Trial information

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    Trial identification
    Sponsor protocol code
    SCRX001-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02674568
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United States, SL6-4UB
    Public contact
    Philip Komarnitsky, Group Medical Director, Abbvie, 1 617 252 4747, philip.komarnitsky@abbvie.com
    Scientific contact
    Philip Komarnitsky, Group Medical Director, Abbvie, 1 617 252 4747, philip.komarnitsky@abbvie.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
    19 Oct 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to investigate the efficacy of rovalpituzumab tesirine as third-line and later (3L+) treatment for subjects with relapsed or refractory DLL3-expressing small cell lung cancer (SCLC) as measured by objective response rate and overall survival.
    Protection of trial subjects
    Participant and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Jan 2016
    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
    United States: 202
    Country: Number of subjects enrolled
    France: 56
    Country: Number of subjects enrolled
    Germany: 37
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Poland: 6
    Country: Number of subjects enrolled
    Spain: 33
    Worldwide total number of subjects
    342
    EEA total number of subjects
    140
    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)
    204
    From 65 to 84 years
    135
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Screening assessments were completed within 14 days of the Day 1 visit.

    Pre-assignment period milestones
    Number of subjects started
    		 342
    Number of subjects completed
    		 339

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Enrolled but not dosed: 3
    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
    		 Rovalpituzumab Tesirine
    Arm description
    		 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.
    Arm type
    		 Experimental

    Investigational medicinal product name
    rovalpituzumab tesirine
    Investigational medicinal product code
    SC16LD6.5
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosing is based on subject actual body weight to the nearest tenth of a kilogram, assessed on Day 1 of each cycle, and administered according to the assigned dose.

    Number of subjects in period 1 [1]
    		Rovalpituzumab Tesirine
    Started
    339
    Delta-like Protein 3 (DLL3) High
    238
    DLL3 Positive
    287
    Completed
    0
    Not completed
    339
         Consent withdrawn by subject
    5
         Physician decision
    2
         Death
    303
         Lost to follow-up
    9
         Other, Not Specified
    20
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 342 subjects were enrolled; 3 subjects were not dosed.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rovalpituzumab Tesirine
    Reporting group description
    		 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.

    Reporting group values
    		 Rovalpituzumab Tesirine Total
    Number of subjects
    		 339 339
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.9 ± 9.36 -
    Gender categorical
    Units: Subjects
        Female
    		 169 169
        Male
    		 170 170
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 1
        Asian
    		 3 3
        Native Hawaiian or Other Pacific Islander
    		 0 0
        Black or African American
    		 11 11
        White
    		 265 265
        More than one race
    		 3 3
        Unknown or Not Reported
    		 56 56
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 10 10
        Not Hispanic or Latino
    		 272 272
        Unknown or Not Reported
    		 57 57

    End points

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    End points reporting groups
    Reporting group title
    Rovalpituzumab Tesirine
    Reporting group description
    		 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.

    Subject analysis set title
    Rovalpituzumab Tesirine: DLL3 High
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Modified Intent to Treat Population: all subjects who received any amount of study drug. 'DLL3 High' (tumors with ≥75% of cells expressing DLL3) participants received 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.

    Subject analysis set title
    Rovalpituzumab Tesirine: DLL3 Positive
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Modified Intent to Treat Population: all subjects who received any amount of study drug. 'DLL3 Positive' (tumors with ≥25% of cells expressing DLL3) subjects received 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.

    Subject analysis set title
    Pharmacokinetic Analysis Population: Initial Treatment Period
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pharmacokinetic Analysis Population: all subjects who receive at least 1 dose of study treatment and at least 1 post-baseline blood sample following a dose of study treatment. Initial Treatment Period: 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (Q6W) for 2 cycles.

    Subject analysis set title
    Pharmacokinetic Analysis Population: Re-Treatment 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pharmacokinetic Analysis Population: all subjects who receive at least 1 dose of study treatment and at least 1 post-baseline blood sample following a dose of study treatment. Re-Treatment 1: 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of retreatment Cycle 1.

    Subject analysis set title
    Pharmacokinetic Analysis Population: Re- Treatment 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pharmacokinetic Analysis Population: all subjects who receive at least 1 dose of study treatment and at least 1 post-baseline blood sample following a dose of study treatment. Re-Treatment 2: 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of retreatment Cycle 2.

    Primary: Objective Response Rate

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    End point title
    		 Objective Response Rate [1]
    End point description
    Objective response is defined as a subject with the best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, prior to receiving any subsequent anticancer therapy and retreatment, and is confirmed by a consecutive response assessment at least 4 weeks (28 days) from the initial determination of CR/PR. Analyzed based on response assessments from both the Independent Review Committee (IRC) and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Primary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) 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: Statistics are presented per protocol.
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    238
    287
    Units: percentage of subjects
    number (confidence interval 95%)
        IRC
    15.5 (11.2 to 20.8)
    14.6 (10.8 to 19.3)
        Investigator
    19.3 (14.5 to 24.9)
    18.8 (14.5 to 23.8)
    No statistical analyses for this end point

    Primary: Overall Survival

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    End point title
    		 Overall Survival [2]
    End point description
    Overall survival is defined as the time from the first dose date to death for any reason. Subjects who were alive at the clinical data cut-off were censored at the last known alive date. Based on Kaplan-Meier estimates.
    End point type
    Primary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    Notes
    [2] - 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: Statistics are presented per protocol.
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    238
    287
    Units: months
        median (confidence interval 95%)
    5.3 (4.7 to 5.8)
    5.3 (4.7 to 5.8)
    No statistical analyses for this end point

    Secondary: Overall Response Rate

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    End point title
    		 Overall Response Rate
    End point description
    Overall response rate is defined as the percentage of subjects with a response of CR or PR, regardless of confirmation, per RECIST v 1.1 prior to receiving any subsequent anticancer therapy and retreatment. Any participants not exhibiting a response (CR or PR) as defined above were considered non-responders. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    238
    287
    Units: percentage of subjects
    number (confidence interval 95%)
        IRC
    23.1 (17.9 to 29.0)
    22.0 (17.3 to 27.2)
        Investigator
    26.9 (21.4 to 33.0)
    25.8 (20.8 to 31.3)
    No statistical analyses for this end point

    Secondary: Duration of Objective Response

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    End point title
    		 Duration of Objective Response
    End point description
    Duration of objective response is defined as the time from the date of first documented CR or PR of subjects with a confirmed response to the documented date of progressive disease (PD) or death, whichever occurred first. Subjects who neither progressed nor died are censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    46 [3]
    54
    Units: months
    median (confidence interval 95%)
        IRC; n=37, 42
    4.0 (3.0 to 4.2)
    4.1 (3.0 to 4.2)
        Investigator; n=46, 54
    4.0 (2.9 to 4.2)
    4.0 (2.9 to 4.3)
    Notes
    [3] - n=subjects who had an objective response
    No statistical analyses for this end point

    Secondary: Progression-Free Survival

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    End point title
    		 Progression-Free Survival
    End point description
    Progression-free survival is defined as the time from the first dose date to the documented date of PD or death, whichever occurred first. Subjects who neither progressed nor died were censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    238
    287
    Units: months
    median (confidence interval 95%)
        IRC
    3.8 (3.3 to 4.1)
    3.8 (3.3 to 4.0)
        Investigator
    3.9 (3.3 to 4.1)
    3.9 (3.3 to 4.0)
    No statistical analyses for this end point

    Secondary: Clinical Benefit Rate

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    End point title
    		 Clinical Benefit Rate
    End point description
    Clinical benefit rate is defined as the percentage of subjects with an overall response of CR or PR or stable disease (SD) with SD of a minimum duration of 42 days from the first dose date. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    238
    287
    Units: percentage of subjects
    number (confidence interval 95%)
        IRC
    73.9 (67.9 to 79.4)
    72.1 (66.6 to 77.2)
        Investigator
    71.0 (64.8 to 76.7)
    68.6 (62.9 to 74.0)
    No statistical analyses for this end point

    Secondary: Duration of Clinical Benefit

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    End point title
    		 Duration of Clinical Benefit
    End point description
    Duration of clinical benefit is defined as the time from the date of first documented CR or PR or SD of ≥ 42 days from first dose date (-7 days to allow for scheduled visit window per the protocol) to the documented date PD or death, whichever occurs first. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine: DLL3 High Rovalpituzumab Tesirine: DLL3 Positive
    Number of subjects analysed
    176 [4]
    207 [5]
    Units: months
    median (confidence interval 95%)
        IRC; n=176, 207
    2.9 (2.8 to 3.2)
    2.9 (2.8 to 3.0)
        Investigator; n=169, 197
    3.0 (2.9 to 3.3)
    3.0 (2.9 to 3.2)
    Notes
    [4] - n= subjects with best overall response of CR or PR or SD
    [5] - n= subjects with best overall response of CR or PR or SD
    No statistical analyses for this end point

    Secondary: Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit

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    End point title
    		 Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29. Cycle 2: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29; End of Treatment (up to Day 29).
    End point values
    		 Pharmacokinetic Analysis Population: Initial Treatment Period Pharmacokinetic Analysis Population: Re-Treatment 1 Pharmacokinetic Analysis Population: Re- Treatment 2
    Number of subjects analysed
    329 [6]
    20 [7]
    2 [8]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1: Day 1, 30 mins pre-infusion; n=329,20,2
    180.9 ± 1215.03
    136.6 ± 923.44
    148.2 ± 81.81
        Cycle 1: Day 1, 30 mins post-infusion; n=329,20,2
    7611.6 ± 1980.49
    6365.5 ± 1763.08
    6690.0 ± 2050.61
        Cycle 1: Day 3; n=317,20,2
    4535.2 ± 1398.49
    3740.5 ± 1454.87
    4630.0 ± 1866.76
        Cycle 1: Day 15; n=300,15,2
    1472.8 ± 573.90
    1323.3 ± 504.33
    1390.0 ± 381.84
        Cycle 1: Day 29; n=279,18,2
    816.3 ± 379.15
    793.8 ± 322.90
    956.5 ± 61.52
        Cycle 2: Day 1, 30 mins pre-infusion; n=223,15,1
    532.2 ± 592.90
    518.6 ± 226.45
    601.0 ± 99999
        Cycle 2: Day 1, 30 mins post-infusion; n=216,15.1
    7535.6 ± 1928.74
    6602.7 ± 1508.23
    7880.0 ± 99999
        Cycle 2: Day 3; n=205,13,1
    4791.1 ± 1373.70
    4670.8 ± 1539.65
    3840.0 ± 99999
        Cycle 2: Day 15; n=206,13,1
    1845.5 ± 688.47
    1857.7 ± 599.65
    2030.0 ± 99999
        Cycle 2: Day 29; n=175,14,1
    1029.3 ± 362.28
    1077.7 ± 362.33
    1300.0 ± 99999
        End of Treatment; n=213,15,2
    558.5 ± 296.09
    686.9 ± 354.68
    679.5 ± 64.35
    Notes
    [6] - n=subjects with an assessment at given time point
    [7] - n=subjects with an assessment at given time point
    [8] - n=subjects with an assessment at given time point. 99999=not applicable (1 subject analyzed)
    No statistical analyses for this end point

    Secondary: Number of Anti-Therapeutic Antibody (ATA) Positive Subjects

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    End point title
    		 Number of Anti-Therapeutic Antibody (ATA) Positive Subjects
    End point description
    All subjects who received rovalpituzumab tesirine and had at least one sample screened for ATA against rovalpituzumab tesirine antibody-drug conjugate (ADC) concentration.
    End point type
    Secondary
    End point timeframe
    up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
    End point values
    		 Rovalpituzumab Tesirine
    Number of subjects analysed
    336 [9]
    Units: subjects
        Positive at any study visit; n=336
    11
        Positive after first dose of study drug; n=276
    3
    Notes
    [9] - n=subjects with ≥ 1 sample screened for ATA against rovalpituzumab tesirine ADC concentration
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Related Adverse Events (TEAEs) During Initial Treatment

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    End point title
    		 Number of Subjects With Treatment-Related Adverse Events (TEAEs) During Initial Treatment
    End point description
    An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant. AE severity was graded using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death. TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
    End point values
    		 Rovalpituzumab Tesirine
    Number of subjects analysed
    339
    Units: subjects
        Any TEAE
    335
        Treatment emergent SAE
    171
        TEAE maximum severity grade 3/4
    179
        TEAE leading to drug wIthdrawal
    25
        TEAE leading to dose interruption
    33
        TEAE leading to dose reduction
    32
        TEAE reasonably possibly related to study drug
    308
        Fatal AE
    34
    No statistical analyses for this end point

    Secondary: Number of Subjects With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment

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    End point title
    		 Number of Subjects With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment
    End point description
    TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
    End point values
    		 Rovalpituzumab Tesirine
    Number of subjects analysed
    339
    Units: subjects
        Any TEAE
    335
        Fatigue
    129
        Photosensitivity reaction
    123
        Pleural effusion
    113
        Oedema peripheral
    105
        Decreased appetite
    102
        Nausea
    88
        Dyspnoea
    83
        Thrombocytopenia
    83
        Constipation
    75
        Vomiting
    59
        Anaemia
    58
        Cough
    54
        Hypoalbuminaemia
    52
        Pericardial effusion
    50
        Abdominal pain
    50
        Asthenia
    50
        Diarrhoea
    47
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug through the end of treatment (EOT; 42 ± 3 days after last dose, or within 7 days of documentation of the decision to discontinue treatment, whichever was later) or 30 days after last study treatment, whichever was later.
    Adverse event reporting additional description
    Mean (SD) duration of follow-up (ie, from the first dose date to the last known date alive or death date) was 29.0 (23.77) weeks.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    Rovalpituzumab Tesirine
    Reporting group description
    		 0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible subjects.

    Serious adverse events
    		 Rovalpituzumab Tesirine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    178 / 339 (52.51%)
         number of deaths (all causes)
    303
         number of deaths resulting from adverse events
    35
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    METASTASES TO PANCREAS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    METASTASIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    CAPILLARY LEAK SYNDROME
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    HAEMORRHAGE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    PERIPHERAL ISCHAEMIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INTERMITTENT CLAUDICATION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SUPERIOR VENA CAVA SYNDROME
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    4 / 339 (1.18%)
         occurrences causally related to treatment / all
    4 / 6
         deaths causally related to treatment / all
    0 / 1
    FATIGUE
         subjects affected / exposed
    5 / 339 (1.47%)
         occurrences causally related to treatment / all
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    8 / 339 (2.36%)
         occurrences causally related to treatment / all
    2 / 14
         deaths causally related to treatment / all
    0 / 6
    GAIT DISTURBANCE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    GENERALISED OEDEMA
         subjects affected / exposed
    8 / 339 (2.36%)
         occurrences causally related to treatment / all
    10 / 10
         deaths causally related to treatment / all
    2 / 2
    OEDEMA PERIPHERAL
         subjects affected / exposed
    8 / 339 (2.36%)
         occurrences causally related to treatment / all
    10 / 10
         deaths causally related to treatment / all
    0 / 0
    PAIN
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    PYREXIA
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    4 / 339 (1.18%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 1
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    HAEMOTHORAX
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    OBSTRUCTIVE AIRWAYS DISORDER
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPOXIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PLEURISY
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    49 / 339 (14.45%)
         occurrences causally related to treatment / all
    54 / 62
         deaths causally related to treatment / all
    1 / 3
    PNEUMONITIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    5 / 5
         deaths causally related to treatment / all
    1 / 1
    PULMONARY HAEMORRHAGE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    1 / 1
    RESPIRATORY FAILURE
         subjects affected / exposed
    7 / 339 (2.06%)
         occurrences causally related to treatment / all
    3 / 11
         deaths causally related to treatment / all
    1 / 3
    RESPIRATORY DISTRESS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    TRACHEAL STENOSIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    DELIRIUM
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    5 / 339 (1.47%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    DISORIENTATION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    4 / 339 (1.18%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    BLOOD URIC ACID INCREASED
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    LIVER FUNCTION TEST INCREASED
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    FALL
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HEAD INJURY
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LIGAMENT SPRAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TRACHEAL HAEMORRHAGE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONITIS CHEMICAL
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    6 / 339 (1.77%)
         occurrences causally related to treatment / all
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    CARDIAC TAMPONADE
         subjects affected / exposed
    4 / 339 (1.18%)
         occurrences causally related to treatment / all
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    CARDIOPULMONARY FAILURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    PERICARDIAL EFFUSION
         subjects affected / exposed
    14 / 339 (4.13%)
         occurrences causally related to treatment / all
    17 / 19
         deaths causally related to treatment / all
    0 / 0
    SINUS BRADYCARDIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    HEMIPARESIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    7 / 339 (2.06%)
         occurrences causally related to treatment / all
    4 / 7
         deaths causally related to treatment / all
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    11 / 339 (3.24%)
         occurrences causally related to treatment / all
    12 / 13
         deaths causally related to treatment / all
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    9 / 339 (2.65%)
         occurrences causally related to treatment / all
    4 / 10
         deaths causally related to treatment / all
    0 / 0
    ASCITES
         subjects affected / exposed
    4 / 339 (1.18%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    1 / 1
    COLITIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INTESTINAL ISCHAEMIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    NAUSEA
         subjects affected / exposed
    7 / 339 (2.06%)
         occurrences causally related to treatment / all
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VOMITING
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    CHOLANGITIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    HEPATOCELLULAR INJURY
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 1
    HEPATIC PAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    HEPATOTOXICITY
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS EXFOLIATIVE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    6 / 339 (1.77%)
         occurrences causally related to treatment / all
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    ERYTHEMA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RENAL IMPAIRMENT
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FLANK PAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RHEUMATOID ARTHRITIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    MYALGIA
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    SPINAL PAIN
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    BACTERIAL INFECTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    CEREBRAL TOXOPLASMOSIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INFECTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OESOPHAGEAL CANDIDIASIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    12 / 339 (3.54%)
         occurrences causally related to treatment / all
    2 / 16
         deaths causally related to treatment / all
    0 / 1
    PULMONARY SEPSIS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    3 / 339 (0.88%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    SEPSIS
         subjects affected / exposed
    6 / 339 (1.77%)
         occurrences causally related to treatment / all
    2 / 8
         deaths causally related to treatment / all
    1 / 4
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    DECREASED APPETITE
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 339 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    6 / 339 (1.77%)
         occurrences causally related to treatment / all
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    2 / 339 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Rovalpituzumab Tesirine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    322 / 339 (94.99%)
    Vascular disorders
    HYPOTENSION
         subjects affected / exposed
    19 / 339 (5.60%)
         occurrences all number
    21
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    48 / 339 (14.16%)
         occurrences all number
    81
    FATIGUE
         subjects affected / exposed
    125 / 339 (36.87%)
         occurrences all number
    170
    FACE OEDEMA
         subjects affected / exposed
    32 / 339 (9.44%)
         occurrences all number
    32
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    19 / 339 (5.60%)
         occurrences all number
    21
    OEDEMA PERIPHERAL
         subjects affected / exposed
    101 / 339 (29.79%)
         occurrences all number
    136
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    83 / 339 (24.48%)
         occurrences all number
    107
    COUGH
         subjects affected / exposed
    56 / 339 (16.52%)
         occurrences all number
    67
    PLEURAL EFFUSION
         subjects affected / exposed
    69 / 339 (20.35%)
         occurrences all number
    84
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    26 / 339 (7.67%)
         occurrences all number
    26
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    20 / 339 (5.90%)
         occurrences all number
    33
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    20 / 339 (5.90%)
         occurrences all number
    27
    WEIGHT DECREASED
         subjects affected / exposed
    32 / 339 (9.44%)
         occurrences all number
    36
    Cardiac disorders
    PERICARDIAL EFFUSION
         subjects affected / exposed
    38 / 339 (11.21%)
         occurrences all number
    40
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    33 / 339 (9.73%)
         occurrences all number
    37
    HEADACHE
         subjects affected / exposed
    18 / 339 (5.31%)
         occurrences all number
    18
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    54 / 339 (15.93%)
         occurrences all number
    88
    THROMBOCYTOPENIA
         subjects affected / exposed
    73 / 339 (21.53%)
         occurrences all number
    140
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    42 / 339 (12.39%)
         occurrences all number
    59
    ABDOMINAL DISTENSION
         subjects affected / exposed
    20 / 339 (5.90%)
         occurrences all number
    21
    NAUSEA
         subjects affected / exposed
    82 / 339 (24.19%)
         occurrences all number
    101
    CONSTIPATION
         subjects affected / exposed
    74 / 339 (21.83%)
         occurrences all number
    87
    DIARRHOEA
         subjects affected / exposed
    46 / 339 (13.57%)
         occurrences all number
    50
    VOMITING
         subjects affected / exposed
    60 / 339 (17.70%)
         occurrences all number
    75
    Skin and subcutaneous tissue disorders
    ERYTHEMA
         subjects affected / exposed
    30 / 339 (8.85%)
         occurrences all number
    37
    DRY SKIN
         subjects affected / exposed
    25 / 339 (7.37%)
         occurrences all number
    28
    PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    119 / 339 (35.10%)
         occurrences all number
    199
    RASH
         subjects affected / exposed
    26 / 339 (7.67%)
         occurrences all number
    30
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    30 / 339 (8.85%)
         occurrences all number
    36
    MYALGIA
         subjects affected / exposed
    22 / 339 (6.49%)
         occurrences all number
    27
    Infections and infestations
    URINARY TRACT INFECTION
         subjects affected / exposed
    27 / 339 (7.96%)
         occurrences all number
    32
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    104 / 339 (30.68%)
         occurrences all number
    124
    DEHYDRATION
         subjects affected / exposed
    19 / 339 (5.60%)
         occurrences all number
    22
    HYPOALBUMINAEMIA
         subjects affected / exposed
    54 / 339 (15.93%)
         occurrences all number
    70
    HYPOKALAEMIA
         subjects affected / exposed
    19 / 339 (5.60%)
         occurrences all number
    23

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Nov 2015
    Allowed subjects who were deriving benefit to receive additional retreatment, beyond a total of 4 cycles, of rovalpituzumab tesirine with approval from the medical monitor; clarification of the 2 primary endpoints; update to inclusion criteria (estimated glomerular filtration rate calculation clarification and update exclusion window of other prior therapy) based on the expected half-life of agents in certain drug class; and clarification that an alternative corticosteroid could be used when dexamethasone was not available.
    14 Mar 2016
    Updates to effective birth control measures; clarification of screening window; language was added to define which hospitalizations will not be considered serious adverse events (SAEs); description of laboratory test result abnormalities and the addition of amylase and lipase to the chemistry panel.
    18 Nov 2016
    Changes were made to reflect study activities and analyses based on DLL3 IHC assays; to limit the number of enrolled 4th-line or later subjects; include efficacy analyses by line of therapy; and clarification that OS, DOR, and PFS will be based on Kaplan-Meier method, including estimates at 6, 9, and 12 months.

    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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