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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers

    Summary
    EudraCT number
    2014-002565-30
    Trial protocol
    FI   CZ   DE   HU   NL   ES   DK   GB  
    Global end of trial date
    21 Feb 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Feb 2021
    First version publication date
    24 Feb 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M14-359
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02264990
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@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
    21 Feb 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.
    Protection of trial subjects
    Subject read and understood the information provided about the study and gave written permission.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Sep 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy
    Long term follow-up duration
    48 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 6
    Country: Number of subjects enrolled
    Australia: 19
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    Czechia: 7
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    Finland: 3
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Hungary: 34
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    Japan: 72
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Netherlands: 31
    Country: Number of subjects enrolled
    New Zealand: 11
    Country: Number of subjects enrolled
    Russian Federation: 74
    Country: Number of subjects enrolled
    South Africa: 19
    Country: Number of subjects enrolled
    Taiwan: 14
    Country: Number of subjects enrolled
    Turkey: 27
    Country: Number of subjects enrolled
    United Kingdom: 62
    Country: Number of subjects enrolled
    United States: 97
    Country: Number of subjects enrolled
    Spain: 54
    Worldwide total number of subjects
    595
    EEA total number of subjects
    149
    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)
    316
    From 65 to 84 years
    278
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were enrolled at 131 sites in 20 countries (Argentina, Australia, Canada, Czech Republic, Denmark, Finland, Germany, Hungary, Israel, Japan, South Korea, Netherlands, New Zealand, Russian Federation, South Africa, Spain, Taiwan, Turkey, United Kingdom, and United States).

    Pre-assignment
    Screening details
    Participants were randomized in a 1:1 ratio to veliparib plus carboplatin and paclitaxel (C/P) or investigator's choice of platinum doublet chemotherapy. Randomization was stratified by smoking status (current vs former), investigators' preferred doublet therapy (C/P vs cisplatin/pemetrexed vs carboplatin/pemetrexed), gender, and ECOG PS (0 vs 1).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Investigator's Choice Chemotherapy
    Arm description
    Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: - Carboplatin at an area under the curve (AUC) of 6 mg/mL*min + paclitaxel 200 mg/m² - Cisplatin 75 mg/m² + pemetrexed 500 mg/m² - Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Arm type
    Active comparator

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered at an AUC 6 mg/mL*min or AUC 5 mg/mL*min on Day 1 of each 21-day cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion 200 mg/m² on Day 1 of each 21-day cycle.

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at 75 mg/m² on Day 1 of each 21-day cycle.

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion, Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at 500 mg/m² Day 1 of each 21-day cycle

    Arm title
    Veliparib + Carboplatin + Paclitaxel
    Arm description
    Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    120 mg orally twice a day on Days -2 to 5 of each 21-day cycle.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered at an AUC 6 mg/mL*min on Day 1 of each 21-day cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at 200 mg/m² on Day 1 of each 21-day cycle.

    Number of subjects in period 1
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Started
    297
    298
    Received Treatment
    288
    293
    Received Maintenance Therapy
    148
    123
    Completed
    37
    39
    Not completed
    260
    259
         Consent withdrawn by subject
    4
    5
         Death
    255
    250
         Other
    -
    1
         Lost to follow-up
    1
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Investigator's Choice Chemotherapy
    Reporting group description
    Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: - Carboplatin at an area under the curve (AUC) of 6 mg/mL*min + paclitaxel 200 mg/m² - Cisplatin 75 mg/m² + pemetrexed 500 mg/m² - Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel
    Reporting group description
    Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Reporting group values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel Total
    Number of subjects
    297 298 595
    Age categorical
    Units: Subjects
        < 65 years
    153 163 316
        ≥ 65 years
    144 135 279
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.1 ( 8.99 ) 62.7 ( 9.02 ) -
    Gender categorical
    Units: Subjects
        Female
    90 92 182
        Male
    207 206 413
    Race
    Units: Subjects
        White
    233 229 462
        Black
    11 11 22
        Asian
    53 57 110
        Other
    0 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    22 26 48
        Not Hispanic or Latino
    275 272 547
    Region
    Units: Subjects
        US and Western EU and Australia and Canada
    177 157 334
        Eastern EU/Russia
    68 88 156
        Japan
    37 35 72
        Other Asia
    15 18 33
    Smoking Status
    Units: Subjects
        Current smoker
    153 152 305
        Past smoker
    144 146 290
    Investigators' Preferred Platinum Doublet Therapy
    The investigator's preferred choice of platinum doublet therapy prior to randomization, which was used as a stratification factor. Note that while the investigator's pre-randomization preferred choice for the doublet is summarized, all participants on the veliparib arm received carboplatin and paclitaxel as chemotherapy.
    Units: Subjects
        Carboplatin/paclitaxel
    71 70 141
        Cisplatin/pemetrexed
    95 100 195
        Carboplatin/pemetrexed
    131 128 259
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care
    Units: Subjects
        Grade 0 (Fully active)
    113 116 229
        Grade 1 (restricted but ambulatory)
    184 182 366
    Lung Subtype Panel (LSP) Assay Results
    LSP positive: Patients with tumors classified as positive for the gene expression-based lung subtype panel (LSP) biomarker LSP negative: Patients with tumors classified as negative for the gene expression-based lung subtype panel (LSP) biomarker
    Units: Subjects
        Not enough sample for LSP status evaluation
    138 126 264
        Sample QC failed
    66 58 124
        LSP positive
    40 40 80
        LSP negative
    53 74 127

    End points

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    End points reporting groups
    Reporting group title
    Investigator's Choice Chemotherapy
    Reporting group description
    Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: - Carboplatin at an area under the curve (AUC) of 6 mg/mL*min + paclitaxel 200 mg/m² - Cisplatin 75 mg/m² + pemetrexed 500 mg/m² - Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel
    Reporting group description
    Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Primary: Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup

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    End point title
    Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
    End point description
    Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
    End point type
    Primary
    End point timeframe
    From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    40 [1]
    40 [2]
    Units: months
        median (confidence interval 95%)
    9.2 (5.1 to 11.7)
    11.2 (7.5 to 15.8)
    Notes
    [1] - LSP-positive subgroup
    [2] - LSP-positive subgroup
    Statistical analysis title
    Primary Analysis of OS in the LSP+ Subgroup
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.113 [4]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.644
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.396
         upper limit
    1.048
    Notes
    [3] - A fixed sequence testing procedure was used for analyses of the primary and secondary efficacy endpoints to control for the familywise error rate. If veliparib plus C/P treatment was not statistically significantly better compared to the investigators' choice of standard therapy for the primary efficacy endpoint of OS in LSP+ participants, then statistical significance would not be declared for any of the secondary efficacy endpoints.
    [4] - Log rank test stratified by ECOG performance status, investigators' preferred platinum therapy, and gender. Statistical significance was determined by a two-sided P value ≤ 0.05.

    Secondary: Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup

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    End point title
    Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup
    End point description
    Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
    End point type
    Secondary
    End point timeframe
    From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    40 [5]
    40 [6]
    Units: months
        median (confidence interval 95%)
    5.2 (2.8 to 6.2)
    6.3 (3.5 to 7.4)
    Notes
    [5] - Lung subtype panel positive subgroup
    [6] - Lung subtype panel positive subgroup
    Statistical analysis title
    Analysis of PFS in LSP+ Subgroup
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    other [7]
    P-value
    = 0.26 [8]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.647
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.388
         upper limit
    1.08
    Notes
    [7] - A fixed sequence testing procedure was used for analyses of the primary and secondary efficacy endpoints to control for the familywise error rate. If veliparib plus C/P treatment was not statistically significantly better than the investigators' choice of standard therapy for the primary efficacy endpoint of OS in LSP+ subjects, then statistical significance will not be declared for any of the secondary efficacy endpoints.
    [8] - Log-rank test stratified by investigator's preferred platinum therapy, gender, and ECOG performance status.

    Secondary: Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup

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    End point title
    Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup
    End point description
    Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new 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, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.
    End point type
    Secondary
    End point timeframe
    Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    40 [9]
    40 [10]
    Units: percentage of participants
        number (confidence interval 95%)
    30.0 (16.6 to 46.5)
    22.5 (10.8 to 38.5)
    Notes
    [9] - Lung subtype panel positive subgroup
    [10] - Lung subtype panel positive subgroup
    Statistical analysis title
    Analysis of ORR in LSP+ Subgroup
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.445 [11]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.23
         upper limit
    1.9
    Notes
    [11] - Logistic regression adjusted for the covariates of ECOG performance status, investigators' preferred platinum therapy, and gender.

    Secondary: Overall Survival in All Participants

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    End point title
    Overall Survival in All Participants
    End point description
    Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
    End point type
    Secondary
    End point timeframe
    From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    297 [12]
    298 [13]
    Units: monthts
        median (confidence interval 95%)
    12.1 (10.0 to 13.7)
    12.1 (10.4 to 14.9)
    Notes
    [12] - Intention-to-treat population
    [13] - Intention-to-treat population
    Statistical analysis title
    Analysis of Overall Survival in All Participants
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    595
    Analysis specification
    Pre-specified
    Analysis type
    other [14]
    P-value
    = 0.846
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.986
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.827
         upper limit
    1.176
    Notes
    [14] - Log rank test stratified by LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.

    Secondary: Progression-free Survival in All Participants

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    End point title
    Progression-free Survival in All Participants
    End point description
    Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
    End point type
    Secondary
    End point timeframe
    From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    297 [15]
    298 [16]
    Units: months
        median (confidence interval 95%)
    6.7 (5.6 to 7.2)
    5.9 (5.0 to 6.5)
    Notes
    [15] - Intention-to-treat population
    [16] - Intention-to-treat population
    Statistical analysis title
    Analysis of PFS in All Participants
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    595
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.473 [17]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.035
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.867
         upper limit
    1.235
    Notes
    [17] - Log rank test stratified by LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.

    Secondary: Objective Response Rate in All Participants

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    End point title
    Objective Response Rate in All Participants
    End point description
    Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new 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, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.
    End point type
    Secondary
    End point timeframe
    Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.
    End point values
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Number of subjects analysed
    297 [18]
    298 [19]
    Units: percentage of participants
        number (confidence interval 95%)
    29.0 (23.9 to 34.5)
    26.2 (21.3 to 31.6)
    Notes
    [18] - Intention-to-treat population
    [19] - Intention-to-treat population
    Statistical analysis title
    Analysis of ORR in All Participants
    Comparison groups
    Investigator's Choice Chemotherapy v Veliparib + Carboplatin + Paclitaxel
    Number of subjects included in analysis
    595
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.409 [20]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.59
         upper limit
    1.24
    Notes
    [20] - Logistic regression adjusted for the covariates of LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 30 days after last dose of study drug (veliparib or investigators' choice of standard chemotherapy); median duration of treatment ranged from 86 to 111 days for each treatment.
    Adverse event reporting additional description
    The as-treated subjects population included all participants who received at least 1 dose of study drug (veliparib/investigator's choice of standard chemotherapy).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Veliparib + Carboplatin + Paclitaxel
    Reporting group description
    Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Reporting group title
    Investigator's Choice Chemotherapy
    Reporting group description
    Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: - Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² - Cisplatin 75 mg/m² + pemetrexed 500 mg/m² - Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Serious adverse events
    Veliparib + Carboplatin + Paclitaxel Investigator's Choice Chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    121 / 293 (41.30%)
    98 / 288 (34.03%)
         number of deaths (all causes)
    249
    252
         number of deaths resulting from adverse events
    24
    22
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC CANCER
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    14 / 293 (4.78%)
    10 / 288 (3.47%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 12
         deaths causally related to treatment / all
    0 / 8
    0 / 4
    MALIGNANT PLEURAL EFFUSION
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO BONE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    4 / 293 (1.37%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO MENINGES
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION MALIGNANT
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    ANEURYSM
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AXILLARY VEIN THROMBOSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOVOLAEMIC SHOCK
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VENOUS THROMBOSIS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 293 (0.34%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CATHETER SITE HAEMORRHAGE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISEASE PROGRESSION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    MALAISE
         subjects affected / exposed
    0 / 293 (0.00%)
    3 / 288 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL SWELLING
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    2 / 2
    0 / 1
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    ANAPHYLACTIC SHOCK
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    3 / 293 (1.02%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    8 / 293 (2.73%)
    7 / 288 (2.43%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    3 / 288 (1.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ORGANISING PNEUMONIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    5 / 293 (1.71%)
    6 / 288 (2.08%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PRODUCTIVE COUGH
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    5 / 293 (1.71%)
    6 / 288 (2.08%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY HAEMORRHAGE
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RESPIRATORY DISTRESS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    RHINORRHOEA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DELIRIUM
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEPRESSION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISORIENTATION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    C-REACTIVE PROTEIN INCREASED
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         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
    FALL
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEART INJURY
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RADIATION OESOPHAGITIS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ARTERIOSPASM CORONARY
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    4 / 293 (1.37%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CARDIAC FAILURE
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CARDIAC FAILURE ACUTE
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    CARDIO-RESPIRATORY ARREST
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    CARDIOPULMONARY FAILURE
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (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
    7 / 293 (2.39%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERICARDITIS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (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
    CEREBRAL INFARCTION
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL ISCHAEMIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COGNITIVE DISORDER
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    7 / 293 (2.39%)
    15 / 288 (5.21%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    13 / 293 (4.44%)
    7 / 288 (2.43%)
         occurrences causally related to treatment / all
    9 / 15
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LYMPHADENITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    6 / 293 (2.05%)
    5 / 288 (1.74%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    2 / 293 (0.68%)
    6 / 288 (2.08%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    APHTHOUS ULCER
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS ISCHAEMIC
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MESENTERIC VEIN THROMBOSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    3 / 293 (1.02%)
    3 / 288 (1.04%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGEAL STENOSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    6 / 293 (2.05%)
    5 / 288 (1.74%)
         occurrences causally related to treatment / all
    4 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    HEPATIC FUNCTION ABNORMAL
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    SUBCUTANEOUS EMPHYSEMA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AZOTAEMIA
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL IMPAIRMENT
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    3 / 293 (1.02%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BONE PAIN
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    APPENDICITIS PERFORATED
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA INFECTIOUS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMPYEMA
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    4 / 293 (1.37%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    LUNG INFECTION
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LYMPHANGITIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERITONSILLAR ABSCESS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    19 / 293 (6.48%)
    8 / 288 (2.78%)
         occurrences causally related to treatment / all
    4 / 26
    0 / 9
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA PSEUDOMONAL
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PSEUDOMONAL SEPSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY SEPSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    1 / 293 (0.34%)
    4 / 288 (1.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    SEPTIC SHOCK
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULAR DEVICE INFECTION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    0 / 293 (0.00%)
    6 / 288 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOGLYCAEMIA
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 288 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    1 / 293 (0.34%)
    2 / 288 (0.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TYPE 2 DIABETES MELLITUS
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 288 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Veliparib + Carboplatin + Paclitaxel Investigator's Choice Chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    275 / 293 (93.86%)
    269 / 288 (93.40%)
    Investigations
    WEIGHT DECREASED
         subjects affected / exposed
    14 / 293 (4.78%)
    24 / 288 (8.33%)
         occurrences all number
    17
    25
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    17 / 293 (5.80%)
    22 / 288 (7.64%)
         occurrences all number
    17
    25
    DYSGEUSIA
         subjects affected / exposed
    19 / 293 (6.48%)
    29 / 288 (10.07%)
         occurrences all number
    20
    33
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    131 / 293 (44.71%)
    42 / 288 (14.58%)
         occurrences all number
    195
    51
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    112 / 293 (38.23%)
    107 / 288 (37.15%)
         occurrences all number
    212
    197
    LEUKOPENIA
         subjects affected / exposed
    43 / 293 (14.68%)
    40 / 288 (13.89%)
         occurrences all number
    77
    77
    NEUTROPENIA
         subjects affected / exposed
    104 / 293 (35.49%)
    89 / 288 (30.90%)
         occurrences all number
    210
    175
    THROMBOCYTOPENIA
         subjects affected / exposed
    76 / 293 (25.94%)
    54 / 288 (18.75%)
         occurrences all number
    155
    102
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    29 / 293 (9.90%)
    30 / 288 (10.42%)
         occurrences all number
    58
    50
    FATIGUE
         subjects affected / exposed
    80 / 293 (27.30%)
    89 / 288 (30.90%)
         occurrences all number
    108
    117
    OEDEMA PERIPHERAL
         subjects affected / exposed
    13 / 293 (4.44%)
    24 / 288 (8.33%)
         occurrences all number
    16
    36
    PYREXIA
         subjects affected / exposed
    15 / 293 (5.12%)
    16 / 288 (5.56%)
         occurrences all number
    17
    21
    Gastrointestinal disorders
    CONSTIPATION
         subjects affected / exposed
    69 / 293 (23.55%)
    92 / 288 (31.94%)
         occurrences all number
    81
    113
    DIARRHOEA
         subjects affected / exposed
    51 / 293 (17.41%)
    47 / 288 (16.32%)
         occurrences all number
    70
    60
    NAUSEA
         subjects affected / exposed
    86 / 293 (29.35%)
    131 / 288 (45.49%)
         occurrences all number
    121
    202
    STOMATITIS
         subjects affected / exposed
    19 / 293 (6.48%)
    30 / 288 (10.42%)
         occurrences all number
    24
    32
    VOMITING
         subjects affected / exposed
    39 / 293 (13.31%)
    73 / 288 (25.35%)
         occurrences all number
    48
    99
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    27 / 293 (9.22%)
    29 / 288 (10.07%)
         occurrences all number
    32
    31
    DYSPNOEA
         subjects affected / exposed
    42 / 293 (14.33%)
    25 / 288 (8.68%)
         occurrences all number
    46
    30
    HICCUPS
         subjects affected / exposed
    17 / 293 (5.80%)
    21 / 288 (7.29%)
         occurrences all number
    27
    29
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    6 / 293 (2.05%)
    15 / 288 (5.21%)
         occurrences all number
    8
    16
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    137 / 293 (46.76%)
    34 / 288 (11.81%)
         occurrences all number
    160
    40
    RASH
         subjects affected / exposed
    13 / 293 (4.44%)
    25 / 288 (8.68%)
         occurrences all number
    16
    29
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    37 / 293 (12.63%)
    30 / 288 (10.42%)
         occurrences all number
    39
    30
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    39 / 293 (13.31%)
    26 / 288 (9.03%)
         occurrences all number
    45
    35
    BACK PAIN
         subjects affected / exposed
    17 / 293 (5.80%)
    22 / 288 (7.64%)
         occurrences all number
    21
    24
    BONE PAIN
         subjects affected / exposed
    15 / 293 (5.12%)
    9 / 288 (3.13%)
         occurrences all number
    21
    13
    MYALGIA
         subjects affected / exposed
    38 / 293 (12.97%)
    17 / 288 (5.90%)
         occurrences all number
    50
    22
    PAIN IN EXTREMITY
         subjects affected / exposed
    15 / 293 (5.12%)
    15 / 288 (5.21%)
         occurrences all number
    17
    19
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    63 / 293 (21.50%)
    79 / 288 (27.43%)
         occurrences all number
    79
    109
    HYPOMAGNESAEMIA
         subjects affected / exposed
    21 / 293 (7.17%)
    16 / 288 (5.56%)
         occurrences all number
    22
    19
    HYPERGLYCAEMIA
         subjects affected / exposed
    24 / 293 (8.19%)
    11 / 288 (3.82%)
         occurrences all number
    24
    15
    HYPONATRAEMIA
         subjects affected / exposed
    16 / 293 (5.46%)
    12 / 288 (4.17%)
         occurrences all number
    18
    14

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Oct 2014
    Added language to include details on pregnancy testing and to clarify drug labeling
    10 Dec 2014
    Changed study phase from Phase 2 to Phase 3 throughout protocol to conform to request by US Food and Drug Administration (FDA); revised investigator's choice stratification factor to preferred platinum doublet chemotherapy to assure balance of subjects suitable for C/P across arms; revised eligibility criteria to reflect exclusion of subjects who have received prior cytotoxic chemotherapy chemoradiotherapy for NSCLC, except adjuvant or neoadjuvant therapy > 12 months prior to C1D-2 for clarification; expanded screening period from 21 to 28 days to reduce number of screen failures that may have occurred due to screening test delays; included Japan-specific protocol language requirements to include facilitation of Japanese sites.
    17 Jul 2015
    Clarified and changed the reference day defining baseline assessment windows throughout; added language regarding starting doses for subjects randomized to the investigator's choice arm; specified that 24 hour urine collection or radioisotope methods were allowed for creatinine clearance/glomerular filtration rate (GFR) measurement; specified washout periods for allowed prior NSCLC treatment in Exclusion Criterion 6; added Japan-specific requirements throughout.
    09 May 2018
    The patient population for the primary endpoint of OS was amended from current smokers to subjects who were positive for the LSP signature; subjects who were LSP positive were to also replace the current smoker population for other key efficacy analyses; updated number of subjects to be enrolled from approximately 525 to 595 subjects.

    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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