Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1/2 Study on the Safety of Rovalpituzumab Tesirine Administered in Combination with Nivolumab or Nivolumab and Ipilimumab for Adults with Extensive-Stage Small Cell Lung Cancer.

    Summary
    EudraCT number
    		 2016-003686-26
    Trial protocol
    		 DE   ES   IT  
    Global end of trial date
    03 Jul 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    17 Jul 2020
    First version publication date
    15 May 2020
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Editorial change to clarify age ranges and an outcome measure description.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M16-300
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03026166
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Abbvie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 011 800-633-9110,
    Scientific contact
    Philip Komarnitsky, MD, PhD, AbbVie, 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
    03 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jul 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to assess the safety of rovalpituzumab tesirine when administered in combination with nivolumab or nivolumab and ipilimumab in adult subjects with extensive-stage small cell lung cancer (SCLC).
    Protection of trial subjects
    All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    United States: 28
    Worldwide total number of subjects
    42
    EEA total number of subjects
    14
    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)
    26
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at 17 clinical study sites in 4 countries: United States, France, Italy, and Germany.

    Pre-assignment
    Screening details
    		 Three study cohorts were planned to enroll approximately 30 subjects in each, including a dose-limiting toxicity (DLT) evaluation phase (the first 12 weeks of any treatment for all subjects) and an expansion phase. However, Cohort 2 was limited to 12 subjects and Cohort 3 was not opened.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Arm description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3). Participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 4 until disease progression.
    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
    Administered by intravenous infusion 0.3 mg/kg, every 6 weeks (q6wk) × 2

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Opdivo®
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion

    Arm title
    		 Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Arm description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 1 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After a 6-week washout, participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.
    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
    Administered by intravenous infusion 0.3 mg/kg, every 6 weeks (q6wk) × 2

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Opdivo®
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion

    Investigational medicinal product name
    Ipilimumab
    Investigational medicinal product code
    Other name
    Yervoy®
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion 1 mg/kg once every 3 weeks

    Number of subjects in period 1
    		Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Started
    30
    12
    Completed
    0
    0
    Not completed
    30
    12
         Physician decision
    2
    -
         Consent withdrawn by subject
    1
    2
         Death
    22
    7
         Other
    1
    -
         Study Terminated by Sponsor
    3
    3
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3). Participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 4 until disease progression.

    Reporting group title
    Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 1 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After a 6-week washout, participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.

    Reporting group values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab Total
    Number of subjects
    		 30 12 42
    Age categorical
    Units: Subjects
        < 40 years
    		 0 1 1
        ≥ 40 to < 60 years
    		 11 5 16
        ≥ 60 years
    		 19 6 25
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.87 ( 8.195 ) 57.25 ( 14.085 ) -
    Gender categorical
    Units: Subjects
        Female
    		 14 5 19
        Male
    		 16 7 23
    Race
    Units: Subjects
        White
    		 29 10 39
        Black or African American
    		 1 1 2
        Not Reported
    		 0 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 2 0 2
        Not Hispanic or Latino
    		 28 11 39
        Not Reported
    		 0 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3). Participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 4 until disease progression.

    Reporting group title
    Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 1 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After a 6-week washout, participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.

    Primary: Number of Participants with Dose-limiting Toxicities (DLTs)

    		 Close Top of page
    End point title
    		 Number of Participants with Dose-limiting Toxicities (DLTs) [1]
    End point description
    Dose-limiting toxicities were defined as any of the following in the 12-week DLT-evaluation period, graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03: ● Grade 4 thrombocytopenia (or Grade 3 thrombocytopenia with bleeding) lasting more than 7 days and/or requiring platelet transfusion ● Grade 4 neutropenia lasting more than 7 days, and/or requiring hematopoietic growth factor rescue, or any febrile neutropenia (Grade 3 or 4 neutropenia with concurrent fever ≥ 38.3°C) ● Grade 4 anemia unrelated to underlying disease ● Clinically significant Grade 3 or 4 non-hematologic laboratory abnormality that did not resolve to Grade 0/1 or baseline within 7 days ● Grade 3 or 4 non-laboratory adverse event (AE), except fatigue, asthenia, nausea, or other manageable constitutional symptom DLT-evaluable participants were those who completed 4 cycles treatment during the DLT period or stopped treatment earlier due to DLT.
    End point type
    Primary
    End point timeframe
    12 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: Comparisons between cohorts were not conducted.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    6 [2]
    6 [3]
    Units: participants
    1
    3
    Notes
    [2] - DLT-evaluable
    [3] - DLT evaluable
    No statistical analyses for this end point

    Primary: Number of Participants with Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Number of Participants with Adverse Events (AEs) [4]
    End point description
    The investigator rated the severity of each AE according to the NCI CTCAE Version 4.03 and according to the following: Grade 1: The AE is transient and easily tolerated by the subject (mild). Grade 2: The AE causes the subject discomfort and interrupts the subject's usual activities (moderate). Grade 3/4: The AE causes considerable interference with the subject's usual activities and may be incapacitating or life-threatening (severe). Grade 5: The AE resulted in death of the subject (severe). The maximum severity of AEs are reported. A serious adverse event was defined as an AE meeting any of the following: - Death - Life-threatening - Resulted in hospitalization or prolongation of hospitalization - Resulted in congenital abnormality - Resulted in persistent or significant disability or incapacity - Was an important medical event requiring medical intervention to prevent a serious outcome. Relationship to study drug was assessed by the Investigator.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug until 100 days after the last dose of study drug; median duration of treatment was 65 days and 53 days in each cohort respectively.
    Notes
    [4] - 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: Comparisons between cohorts were not conducted.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    30
    12
    Units: participants
        Any adverse event
    30
    12
        Drug-related adverse event
    29
    12
        Serious adverse event
    23
    9
        Drug-related serious adverse event
    13
    6
        Grade 3 adverse event
    11
    7
        Grade 4 adverse event
    1
    1
        Grade 5 adverse event
    14
    4
        Drug-related Grade 3 adverse event
    9
    10
        Drug-related Grade 4 adverse event
    3
    1
        Drug-related Grade 5 adverse event
    4
    0
        AE leading to study drug withdrawal
    12
    6
        AE leading to treatment interruption
    18
    8
        AE leading to dose reduction
    0
    1
        Drug-related AE leading to study drug withdrawal
    9
    4
        Drug-related AE leading to treatment interruption
    17
    8
        Drug-related AE leading to dose reduction
    0
    0
    No statistical analyses for this end point

    Secondary: Objective Response Rate

    		 Close Top of page
    End point title
    		 Objective Response Rate
    End point description
    Treatment response was assessed by radiographic tumor evaluations conducted by a central radiology review. Objective response rate (ORR) is defined as the percentage of participants whose best overall response is either a confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Partial response (PR): A ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been confirmed at least 4 weeks (28 days) from the initial determination per RECIST v 1.1. The Efficacy Analysis Set includes participants who received at least one dose of study drug, had a target lesion identified at baseline, and either had at least 1 post-dose tumor assessment or discontinued treatment due to AE, progressive disease (PD) or death.
    End point type
    Secondary
    End point timeframe
    Cohort 1: at Week 6, Week 13, and every 8 weeks thereafter; Cohort 2: at Week 6, Week 12, Week 18, and every 8 weeks thereafter, up to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    29 [5]
    11 [6]
    Units: percentage of participants
        number (confidence interval 95%)
    27.6 (12.7 to 47.2)
    36.4 (10.9 to 69.2)
    Notes
    [5] - Efficacy Analysis Set
    [6] - Efficacy Analysis Set
    No statistical analyses for this end point

    Secondary: Duration of Response

    		 Close Top of page
    End point title
    		 Duration of Response
    End point description
    Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by central radiology review and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Based on Kaplan-Meier estimate. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 0.5 cm, or the unequivocal progression of non-target lesions, or the appearance of one or more new lesions. The analysis includes participants in the Efficacy Analysis Set with a best overall response of unconfirmed CR or PR. "99999" indicates a value that could not be estimated.
    End point type
    Secondary
    End point timeframe
    Cohort 1: at Week 6, Week 13, and every 8 weeks thereafter; Cohort 2: at Week 6, Week 12, Week 18 and every 8 weeks thereafter, up to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    10 [7]
    6 [8]
    Units: months
        median (confidence interval 95%)
    3.8 (1.6 to 5.6)
    3.3 (1.4 to 99999)
    Notes
    [7] - Efficacy analysis set participants with unconfirmed CR or PR
    [8] - Efficacy analysis set participants with unconfirmed CR or PR
    No statistical analyses for this end point

    Secondary: Progression-Free Survival

    		 Close Top of page
    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, based on central radiology review according to RECIST v 1.1. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Based on Kaplan-Meier estimates. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 0.5 cm, or the unequivocal progression of non-target lesions, or the appearance of one or more new lesions. Efficacy Analysis Set.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    29 [9]
    11 [10]
    Units: months
        median (confidence interval 95%)
    4.8 (3.2 to 5.3)
    4.1 (1.3 to 6.0)
    Notes
    [9] - Efficacy Analysis Set
    [10] - Efficacy Analysis Set
    No statistical analyses for this end point

    Secondary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival
    End point description
    Overall survival is defined as the time from the first dose date to death for any reason. Participants who were still alive were censored at the last known alive date. Based on Kaplan-Meier estimates. The Full Analysis Set includes participants who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to the end of follow-up; median duration on follow-up was 31.7 and 48.0 weeks in each cohort respectively.
    End point values
    		 Cohort 1: Rovalpituzumab Tesirine and Nivolumab Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Number of subjects analysed
    30 [11]
    12 [12]
    Units: months
        median (confidence interval 95%)
    7.4 (5.0 to 9.1)
    11.0 (2.3 to 17.0)
    Notes
    [11] - Full analysis set
    [12] - Full analysis set
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of study drug until 100 days after the last dose of study drug; median duration of treatment was 65 days and 53 days in each cohort respectively.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine IV 6 weeks apart (Day 1 of Cycles 1 and 3), nivolumab 1 mg/kg every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5), and ipilimumab 1 mg/kg IV every 3 weeks for 4 cycles beginning on Cycle 2 (Day 1 of Cycles 2-5). After a 6-week washout, participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 6 until disease progression.

    Reporting group title
    Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Reporting group description
    		 Participants received 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3). Participants then received maintenance therapy with 480 mg nivolumab IV once every 4 weeks from Cycle 4 until disease progression.

    Serious adverse events
    		 Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 12 (75.00%)
    23 / 30 (76.67%)
         number of deaths (all causes)
    8
    26
         number of deaths resulting from adverse events
    4
    14
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    2 / 12 (16.67%)
    8 / 30 (26.67%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 8
         deaths causally related to treatment / all
    0 / 2
    1 / 8
    Vascular disorders
    HYPOTENSION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    CONDITION AGGRAVATED
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FACE OEDEMA
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERALISED OEDEMA
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 12 (0.00%)
    8 / 30 (26.67%)
         occurrences causally related to treatment / all
    0 / 0
    11 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 30 (10.00%)
         occurrences causally related to treatment / all
    1 / 1
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    PNEUMOTHORAX
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CARDIAC TAMPONADE
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    ISCHAEMIC STROKE
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERONEAL NERVE PALSY
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    DISSEMINATED INTRAVASCULAR COAGULATION
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ASCITES
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    AUTOIMMUNE HEPATITIS
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATOCELLULAR INJURY
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH MACULO-PAPULAR
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Musculoskeletal and connective tissue disorders
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    EMPYEMA
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA FUNGAL
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RESPIRATORY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    SEPSIS
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 2: Rovalpituzumab Tesirine and Nivolumab + Ipilimumab Cohort 1: Rovalpituzumab Tesirine and Nivolumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 12 (100.00%)
    30 / 30 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR PAIN
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Vascular disorders
    FLUSHING
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    HYPERTENSION
         subjects affected / exposed
    0 / 12 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    0
    5
    HYPOTENSION
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 30 (13.33%)
         occurrences all number
    2
    5
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    3 / 12 (25.00%)
    5 / 30 (16.67%)
         occurrences all number
    5
    14
    CHEST PAIN
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    FACE OEDEMA
         subjects affected / exposed
    2 / 12 (16.67%)
    6 / 30 (20.00%)
         occurrences all number
    2
    8
    FATIGUE
         subjects affected / exposed
    4 / 12 (33.33%)
    11 / 30 (36.67%)
         occurrences all number
    5
    14
    LOCALISED OEDEMA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    OEDEMA PERIPHERAL
         subjects affected / exposed
    3 / 12 (25.00%)
    12 / 30 (40.00%)
         occurrences all number
    4
    18
    PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    4
    PYREXIA
         subjects affected / exposed
    3 / 12 (25.00%)
    5 / 30 (16.67%)
         occurrences all number
    3
    7
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    4
    DYSPNOEA
         subjects affected / exposed
    5 / 12 (41.67%)
    11 / 30 (36.67%)
         occurrences all number
    5
    17
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HICCUPS
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    HYPOXIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    PLEURAL EFFUSION
         subjects affected / exposed
    5 / 12 (41.67%)
    7 / 30 (23.33%)
         occurrences all number
    7
    13
    PRODUCTIVE COUGH
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    PULMONARY HYPERTENSION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    RHINORRHOEA
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    WHEEZING
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    DEPRESSION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    INSOMNIA
         subjects affected / exposed
    0 / 12 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    0
    6
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    6
    AMYLASE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    0
    5
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    5
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    4
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    BLOOD THYROID STIMULATING HORMONE DECREASED
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    FALL
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    PALPITATIONS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    1 / 12 (8.33%)
    7 / 30 (23.33%)
         occurrences all number
    2
    8
    SINUS TACHYCARDIA
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    TACHYCARDIA
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    DYSGEUSIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    HEADACHE
         subjects affected / exposed
    0 / 12 (0.00%)
    6 / 30 (20.00%)
         occurrences all number
    0
    6
    HEMIPARESIS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HYPERAESTHESIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    NEURALGIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    6 / 12 (50.00%)
    10 / 30 (33.33%)
         occurrences all number
    6
    17
    LEUKOCYTOSIS
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    LYMPHOPENIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    NEUTROPENIA
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    THROMBOCYTOPENIA
         subjects affected / exposed
    5 / 12 (41.67%)
    9 / 30 (30.00%)
         occurrences all number
    7
    14
    Eye disorders
    CATARACT
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    DRY EYE
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    EYE PRURITUS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    EYELID OEDEMA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    OCULAR HYPERAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    PERIORBITAL OEDEMA
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    RETINOPATHY
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    VISION BLURRED
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    VISUAL IMPAIRMENT
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    XEROPHTHALMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    ABDOMINAL PAIN
         subjects affected / exposed
    2 / 12 (16.67%)
    7 / 30 (23.33%)
         occurrences all number
    2
    7
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    ASCITES
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    COLITIS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    CONSTIPATION
         subjects affected / exposed
    3 / 12 (25.00%)
    8 / 30 (26.67%)
         occurrences all number
    3
    9
    DIARRHOEA
         subjects affected / exposed
    4 / 12 (33.33%)
    4 / 30 (13.33%)
         occurrences all number
    4
    4
    DRY MOUTH
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    ERUCTATION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    LIP DRY
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    NAUSEA
         subjects affected / exposed
    1 / 12 (8.33%)
    5 / 30 (16.67%)
         occurrences all number
    1
    6
    RETCHING
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    VOMITING
         subjects affected / exposed
    3 / 12 (25.00%)
    7 / 30 (23.33%)
         occurrences all number
    3
    10
    Hepatobiliary disorders
    HEPATIC FUNCTION ABNORMAL
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HEPATOCELLULAR INJURY
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    LIVER INJURY
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    BLISTER
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    DRY SKIN
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    ERYTHEMA
         subjects affected / exposed
    2 / 12 (16.67%)
    6 / 30 (20.00%)
         occurrences all number
    2
    8
    PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    2 / 12 (16.67%)
    7 / 30 (23.33%)
         occurrences all number
    4
    10
    PRURITUS
         subjects affected / exposed
    3 / 12 (25.00%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    PRURITUS GENERALISED
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    RASH
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    RASH MACULAR
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    4 / 12 (33.33%)
    5 / 30 (16.67%)
         occurrences all number
    6
    5
    SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    PROTEINURIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Endocrine disorders
    HYPERTHYROIDISM
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    HYPOTHYROIDISM
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 30 (10.00%)
         occurrences all number
    2
    3
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 12 (8.33%)
    5 / 30 (16.67%)
         occurrences all number
    2
    7
    BACK PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    FLANK PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    0
    4
    MYALGIA
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    NECK PAIN
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    CONJUNCTIVITIS
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    HORDEOLUM
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    ORAL CANDIDIASIS
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 30 (10.00%)
         occurrences all number
    1
    3
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    SINUSITIS
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    SKIN BACTERIAL INFECTION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 12 (16.67%)
    4 / 30 (13.33%)
         occurrences all number
    2
    5
    VIRAL INFECTION
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    5 / 12 (41.67%)
    9 / 30 (30.00%)
         occurrences all number
    6
    11
    DEHYDRATION
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    HYPERCALCAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 30 (13.33%)
         occurrences all number
    1
    4
    HYPERKALAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HYPERLIPASAEMIA
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    2 / 12 (16.67%)
    6 / 30 (20.00%)
         occurrences all number
    2
    10
    HYPOCALCAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 12 (0.00%)
    5 / 30 (16.67%)
         occurrences all number
    0
    5
    HYPOMAGNESAEMIA
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 30 (13.33%)
         occurrences all number
    1
    4
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 30 (10.00%)
         occurrences all number
    6
    3
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2016
    Defined target level of activity based on overall response rate (ORR) that would help inform decisions on program development; clarification of contraception recommendations; recommendations provided in the Study May Proceed Memorandum dated 08 December 2016 were added, including updated Day 2 assessments for PK and additional PK and anti-therapeutic antibody-related analytes of rovalpituzumab tesirine; and other administrative corrections and clarifications.
    01 Dec 2017
    Most amendment changes were revisions to enhance recruitment; these included clarifications to the prior therapy eligibility requirements and simultaneous cohort enrollment. Additionally, the following items were clarified: dosing schedules; required premedication and post-medication; blood tumor markers and biomarkers collection; the DLT evaluation period; dose delay criteria; washout period and telephone follow-up procedures; radiographic assessment; and permanent treatment discontinuation criteria including treatment continuation beyond progression and dosing interruption; and other administrative corrections and clarifications.

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

    European Medicines Agency © 1995-Sat May 04 04:29:00 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA