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   44334   clinical trials with a EudraCT protocol, of which   7366   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 II, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY EVALUATING THE SAFETY AND EFFICACY OF MEGF0444A IN COMBINATION WITH CARBOPLATIN, PACLITAXEL AND BEVACIZUMAB IN PATIENTS WITH ADVANCED OR RECURRENT NON-SQUAMOUS NON-SMALL CELL LUNG CANCER WHO HAVE NOT RECEIVED PRIOR CHEMOTHERAPY FOR ADVANCED DISEASE

    Summary
    EudraCT number
    		 2011-000711-85
    Trial protocol
    		 CZ   HU  
    Global end of trial date
    29 Aug 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Jul 2016
    First version publication date
    02 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GO27811
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01366131
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Genentech Study ID: MEF4984g
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124,, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.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
    12 Mar 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Aug 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This is a Phase II, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of MEGF0444A combined with paclitaxel + carboplatin + bevacizumab therapy in participants with histologically or cytologically documented inoperable, locally advanced, metastatic (Stage IV), or recurrent non-squamous non-small cell lung cancer (NSCLC). The primary objective of this trial was to evaluate the efficacy of MEGF0444A in combination with carboplatin, paclitaxel, and bevacizumab in participants with advanced or recurrent non-squamous NSCLC, as measured by progression free survival (PFS).
    Protection of trial subjects
    This study was conducted in accordance with the United States Food and Drug Administration (USFDA) regulations, the International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP), and applicable local, state, and federal laws, as well as other applicable country laws.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Jun 2011
    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
    Australia: 3
    Country: Number of subjects enrolled
    United States: 33
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Czech Republic: 2
    Country: Number of subjects enrolled
    France: 24
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Hungary: 20
    Worldwide total number of subjects
    104
    EEA total number of subjects
    68
    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)
    57
    From 65 to 84 years
    47
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 104 participants who met the study selection criteria were enrolled and randomized to one of the two treatment arms, MEGF0444A and Placebo. Control arm (52 participants): Placebo + Paclitaxel + Carboplatin + Bevacizumab; Experimental arm (52 participants): MEGF044A + Paclitaxel + Carboplatin Bevacizumab.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MEGF0444A
    Arm description
    		 Participants received paclitaxel 200 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1, carboplatin (at doses to achieve an area under the concentration time curve [AUC] of 6 milligrams/milliliter*minute [mg/mL*min]) IV infusion on Day 1, and bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion on Day 1 of each 21-day cycle. Participants also received MEGF0444A at a fixed dose of 600 mg IV infusion on Day 1 of Cycle 1, followed by subsequent doses of 600 mg every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by MEGF0444A. Paclitaxel and carboplatin were administered until disease progression (DP) or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and MEGF0444A were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 6 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 6 cycles.

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Investigational medicinal product name
    MEGF0444A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants also received MEGF0444A at a fixed dose of 600 mg IV infusion on Day 1 of Cycle 1, followed by subsequent doses of 600 mg every 21 days until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Arm title
    		 Placebo
    Arm description
    		 Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1, carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1, and bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle. Participants also received placebo matched to MEGF0444A IV infusion on Day 1 of Cycle 1, followed by subsequent placebo administration every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by placebo. Paclitaxel and carboplatin were administered until DP or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and placebo were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 6 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 6 cycles.

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received placebo matched to MEGF0444A IV infusion on Day 1 of Cycle 1, followed by subsequent placebo administration every 21 days until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Number of subjects in period 1
    		MEGF0444A Placebo
    Started
    52
    52
    Treated
    52
    51
    Completed
    0
    0
    Not completed
    52
    52
         Consent withdrawn by subject
    1
    3
         Physician decision
    -
    1
         Randomized not treated
    -
    1
         Death
    23
    18
         Study terminated by sponsor
    23
    28
         Unspecified
    4
    1
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MEGF0444A
    Reporting group description
    		 Participants received paclitaxel 200 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1, carboplatin (at doses to achieve an area under the concentration time curve [AUC] of 6 milligrams/milliliter*minute [mg/mL*min]) IV infusion on Day 1, and bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion on Day 1 of each 21-day cycle. Participants also received MEGF0444A at a fixed dose of 600 mg IV infusion on Day 1 of Cycle 1, followed by subsequent doses of 600 mg every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by MEGF0444A. Paclitaxel and carboplatin were administered until disease progression (DP) or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and MEGF0444A were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1, carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1, and bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle. Participants also received placebo matched to MEGF0444A IV infusion on Day 1 of Cycle 1, followed by subsequent placebo administration every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by placebo. Paclitaxel and carboplatin were administered until DP or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and placebo were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Reporting group values
    		 MEGF0444A Placebo Total
    Number of subjects
    		 52 52 104
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.9 ( 8.6 ) 62.3 ( 9.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 19 18 37
        Male
    		 33 34 67

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    MEGF0444A
    Reporting group description
    		 Participants received paclitaxel 200 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1, carboplatin (at doses to achieve an area under the concentration time curve [AUC] of 6 milligrams/milliliter*minute [mg/mL*min]) IV infusion on Day 1, and bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion on Day 1 of each 21-day cycle. Participants also received MEGF0444A at a fixed dose of 600 mg IV infusion on Day 1 of Cycle 1, followed by subsequent doses of 600 mg every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by MEGF0444A. Paclitaxel and carboplatin were administered until disease progression (DP) or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and MEGF0444A were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1, carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1, and bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle. Participants also received placebo matched to MEGF0444A IV infusion on Day 1 of Cycle 1, followed by subsequent placebo administration every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by placebo. Paclitaxel and carboplatin were administered until DP or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and placebo were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Primary: Percentage of Participants With Disease Progression (DP) or Death

    		 Close Top of page
    End point title
    		 Percentage of Participants With Disease Progression (DP) or Death [1]
    End point description
    PFS was defined as time from randomization to the first occurrence of documented DP (according to Response Evaluation Criteria in Solid Tumors [RECIST], Version 1.1 [v 1.1]) or death from any cause on study, whichever occurred earlier, as determined by investigator. Death on study is defined as death from any cause within 30 days of last study treatment. Determination of DP for the purpose of treatment decisions and timing of the primary analysis was based on investigator assessment, using RECIST v 1.1. Tumor assessment was performed by RECIST v 1.1. DP was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression. Analysis population included all participants who were randomized.
    End point type
    Primary
    End point timeframe
    Baseline up to DP or death, whichever occurred first (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months])
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this outcome.
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    52
    52
    Units: Percentage of participants
        number (not applicable)
    75
    44.2
    No statistical analyses for this end point

    Primary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS was defined as time from randomization to the first occurrence of documented DP (according to RECIST v 1.1) or death from any cause on study, whichever occurred earlier, as determined by investigator. DP was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Median and the 95% confidence interval (CI) were estimated using Kaplan-Meier survival methodology. Analysis population included all participants who were randomized.
    End point type
    Primary
    End point timeframe
    Baseline up to DP or death, whichever occurred first (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months])
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    52
    52
    Units: Months
        median (confidence interval 95%)
    6.7 (5.68 to 7.43)
    8.1 (5.88 to 11.14)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The unstratified Cox proportional hazard model was used to estimate the hazard ratio (the magnitude of the treatment effect) and the corresponding 95% CI.
    Comparison groups
    Placebo v MEGF0444A
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0466
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.686
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.003
         upper limit
    		 2.835

    Secondary: Percentage of Participants With Objective Response (OR)

    		 Close Top of page
    End point title
    		 Percentage of Participants With Objective Response (OR)
    End point description
    Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) as per RECIST v 1.1. Confirmed responses: persist on repeat imaging study at least 4 weeks after initial documentation of response. CR: disappearance of all target and non-target lesions; normalization of tumor markers. Non-pathological lymph nodes: short axis measures less than (<) 10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. DP: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate absolute increase of at least 5 mm. Appearance of one or more new lesions is also considered progression. Analysis population included all participants who were randomized.
    End point type
    Secondary
    End point timeframe
    Baseline up to DP or death, whichever occurred first (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months])
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    52
    52
    Units: Percentage of participants
        number (not applicable)
    28.8
    55.8
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    MEGF0444A v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0095
    Method
    		 Logrank
    Confidence interval

    Secondary: Duration of Objective Response

    		 Close Top of page
    End point title
    		 Duration of Objective Response
    End point description
    Duration of objective response was defined as the first occurrence of objective response to DP or death due to any cause on study. DP was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to DP or death, whichever occurred first (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months])
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [2]
    0 [3]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [2] - Data not available due to early study termination.
    [3] - Data not available due to early study termination.
    No statistical analyses for this end point

    Secondary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival
    End point description
    Overall survival was defined as the time from randomization until death from any cause. All deaths were included, without regard to whether they occur on study or following treatment discontinuation. Overall survival was censored at the date of last contact for participants who were alive. Analysis population included all participants who were randomized. The number 99999 signified data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline until death (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months], and thereafter every 3 months until death [up to approximately 2.75 years])
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    52
    52
    Units: Months
        median (confidence interval 95%)
    99999 (9.69 to 99999)
    12.4 (11.89 to 12.52)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The unstratified Cox proportional hazard model was used to estimate the hazard ratio (the magnitude of the treatment effect) and the corresponding 95% CI.
    Comparison groups
    MEGF0444A v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8465
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.076
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.525
         upper limit
    		 2.206

    Secondary: Percentage of Participants Who Died

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Died
    End point description
    Analysis population included all participants who were randomized.
    End point type
    Secondary
    End point timeframe
    Baseline until death (assessed at baseline, Day 15 of each cycle [21-day cycles], end of treatment or early termination [up to 24 months], and thereafter every 3 months until death [up to approximately 2.75 years])
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    52
    52
    Units: Percentage of participants
        number (not applicable)
    28.8
    28.8
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores

    		 Close Top of page
    End point title
    		 Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores
    End point description
    EORTC QLQ-C30: included global health status/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global QOL/functional scales indicates better level of QOL/functioning, or a higher score for symptom scale indicates greater degree of symptoms. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to early termination or end of treatment (up to 24 months)
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: Units on a scale
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [4] - Data not available due to early study termination.
    [5] - Data not available due to early study termination.
    No statistical analyses for this end point

    Secondary: Change From Baseline in EORTC QLQ Lung Cancer Module 13 (LC-13)

    		 Close Top of page
    End point title
    		 Change From Baseline in EORTC QLQ Lung Cancer Module 13 (LC-13)
    End point description
    EORTC QLQ-LC13: consisted of 13 questions with one symptom scale for dyspnea of 3 items and 10 single items (cough, haemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain, pain medication). Questions used 4-point scale (1 'Not at all' to 4 'Very much'. Scores were averaged and transformed to 0-100 scale; higher score = greater degree of symptoms. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to early termination or end of treatment (up to 24 months)
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: Units on a scale
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [6] - Data not available due to early study termination.
    [7] - Data not available due to early study termination.
    No statistical analyses for this end point

    Secondary: Delay in Deterioration of Disease Symptoms of Cough, Dyspnea, Pain

    		 Close Top of page
    End point title
    		 Delay in Deterioration of Disease Symptoms of Cough, Dyspnea, Pain
    End point description
    Delay in deterioration of disease symptoms was defined as time taken for clinically meaningful change (greater than or equal to [>/=] 10 points) in each of the symptoms: cough, dyspnea and pain. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to early termination or end of treatment (up to 24 months)
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [8]
    0 [9]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [8] - Data not available due to early study termination.
    [9] - Data not available due to early study termination.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Clinically Meaningful Impact on Global Health Status/QOL and Functional Scales by EORTC QLQ-C30 Improvement Category

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinically Meaningful Impact on Global Health Status/QOL and Functional Scales by EORTC QLQ-C30 Improvement Category
    End point description
    EORTC QLQ-C30: included global health status/QOL, functional scales (physical, role, cognitive, emotional, and social). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); health status/QOL questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global QOL/functional scales indicates better level of QOL/functioning. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to early termination or end of treatment (up to 24 months)
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [10]
    0 [11]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [10] - Data not available due to early study termination.
    [11] - Data not available due to early study termination.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Clinically Meaningful Treatment-Related Symptoms

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinically Meaningful Treatment-Related Symptoms
    End point description
    Clinically meaningful treatment-related symptoms was defined as participants reporting “quite a bit” or “very much” symptoms for the symptom scales. Symptom scale (fatigue, pain, nausea/vomiting) scores averaged, transformed to 0-100 scale; higher score=greater degree of symptoms. Data not available as the study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    End point type
    Secondary
    End point timeframe
    Baseline up to early termination or end of treatment (up to 24 months)
    End point values
    		 MEGF0444A Placebo
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Percentage of Participants
        number (not applicable)
    Notes
    [12] - Data not available due to early study termination.
    [13] - Data not available due to early study termination.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Day 1 Cycle 1) up to end of treatment or early termination (up to 24 months)
    Adverse event reporting additional description
    Safety population included all randomized participants who received at least one dose of study treatment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    MEGF0444A
    Reporting group description
    		 Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1, carboplatin (at doses to achieve an AUC of 6 mg/mL*min] IV infusion on Day 1, and bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle. Participants also received MEGF0444A at a fixed dose of 600 mg IV infusion on Day 1 of Cycle 1, followed by subsequent doses of 600 mg every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by MEGF0444A. Paclitaxel and carboplatin were administered until DP or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and MEGF0444A were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received paclitaxel 200 mg/m^2 IV infusion on Day 1, carboplatin (at doses to achieve an AUC of 6 mg/mL*min) IV infusion on Day 1, and bevacizumab 15 mg/kg IV infusion on Day 1 of each 21-day cycle. Participants also received placebo matched to MEGF0444A IV infusion on Day 1 of Cycle 1, followed by subsequent placebo administration every 21 days. The preferred order of study treatment administration was paclitaxel, carboplatin, and bevacizumab, followed by placebo. Paclitaxel and carboplatin were administered until DP or unacceptable toxicity, for a maximum of 6 cycles; bevacizumab and placebo were administered until DP or unacceptable toxicity, for a maximum of 24 months (34 cycles).

    Serious adverse events
    		 MEGF0444A Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    29 / 52 (55.77%)
    30 / 51 (58.82%)
         number of deaths (all causes)
    24
    18
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    5 / 52 (9.62%)
    4 / 51 (7.84%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lung lobectomy
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracotomy
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         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
    General physical health deterioration
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 52 (1.92%)
    4 / 51 (7.84%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 52 (3.85%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cough
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Inflammatory marker increased
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         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
    Femur fracture
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis radiation
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    3 / 52 (5.77%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Anaemia
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 52 (3.85%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         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
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 52 (3.85%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Febrile infection
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MEGF0444A Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    50 / 52 (96.15%)
    49 / 51 (96.08%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 52 (17.31%)
    13 / 51 (25.49%)
         occurrences all number
    10
    19
    Hypotension
         subjects affected / exposed
    2 / 52 (3.85%)
    3 / 51 (5.88%)
         occurrences all number
    2
    5
    Flushing
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    4
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    17 / 52 (32.69%)
    17 / 51 (33.33%)
         occurrences all number
    37
    33
    Fatigue
         subjects affected / exposed
    24 / 52 (46.15%)
    18 / 51 (35.29%)
         occurrences all number
    31
    27
    Pyrexia
         subjects affected / exposed
    7 / 52 (13.46%)
    3 / 51 (5.88%)
         occurrences all number
    9
    3
    Chest pain
         subjects affected / exposed
    5 / 52 (9.62%)
    3 / 51 (5.88%)
         occurrences all number
    5
    4
    Mucosal inflammation
         subjects affected / exposed
    4 / 52 (7.69%)
    4 / 51 (7.84%)
         occurrences all number
    5
    4
    Pain
         subjects affected / exposed
    5 / 52 (9.62%)
    3 / 51 (5.88%)
         occurrences all number
    6
    3
    Chills
         subjects affected / exposed
    5 / 52 (9.62%)
    2 / 51 (3.92%)
         occurrences all number
    6
    2
    Oedema Peripheral
         subjects affected / exposed
    4 / 52 (7.69%)
    2 / 51 (3.92%)
         occurrences all number
    4
    3
    Gait disturbance
         subjects affected / exposed
    3 / 52 (5.77%)
    0 / 51 (0.00%)
         occurrences all number
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    13 / 52 (25.00%)
    13 / 51 (25.49%)
         occurrences all number
    14
    16
    Epistaxis
         subjects affected / exposed
    13 / 52 (25.00%)
    12 / 51 (23.53%)
         occurrences all number
    19
    14
    Cough
         subjects affected / exposed
    11 / 52 (21.15%)
    5 / 51 (9.80%)
         occurrences all number
    12
    5
    Oropharyngeal pain
         subjects affected / exposed
    4 / 52 (7.69%)
    4 / 51 (7.84%)
         occurrences all number
    4
    5
    Productive cough
         subjects affected / exposed
    5 / 52 (9.62%)
    2 / 51 (3.92%)
         occurrences all number
    6
    2
    Dysphonia
         subjects affected / exposed
    2 / 52 (3.85%)
    4 / 51 (7.84%)
         occurrences all number
    2
    5
    Haemoptysis
         subjects affected / exposed
    4 / 52 (7.69%)
    2 / 51 (3.92%)
         occurrences all number
    4
    2
    Dyspnoea exertional
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    4
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    3 / 52 (5.77%)
    8 / 51 (15.69%)
         occurrences all number
    3
    8
    Insomnia
         subjects affected / exposed
    1 / 52 (1.92%)
    12 / 51 (23.53%)
         occurrences all number
    1
    12
    Depression
         subjects affected / exposed
    2 / 52 (3.85%)
    3 / 51 (5.88%)
         occurrences all number
    2
    4
    Investigations
    Weight decreased
         subjects affected / exposed
    6 / 52 (11.54%)
    9 / 51 (17.65%)
         occurrences all number
    7
    9
    Neutrophil count decreased
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 51 (5.88%)
         occurrences all number
    1
    5
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 51 (5.88%)
         occurrences all number
    1
    3
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    15 / 52 (28.85%)
    16 / 51 (31.37%)
         occurrences all number
    21
    18
    Peripheral sensory neuropathy
         subjects affected / exposed
    6 / 52 (11.54%)
    7 / 51 (13.73%)
         occurrences all number
    12
    14
    Polyneuropathy
         subjects affected / exposed
    8 / 52 (15.38%)
    4 / 51 (7.84%)
         occurrences all number
    17
    8
    Headache
         subjects affected / exposed
    8 / 52 (15.38%)
    5 / 51 (9.80%)
         occurrences all number
    16
    5
    Dysgeusia
         subjects affected / exposed
    2 / 52 (3.85%)
    11 / 51 (21.57%)
         occurrences all number
    2
    13
    Paraesthesia
         subjects affected / exposed
    6 / 52 (11.54%)
    3 / 51 (5.88%)
         occurrences all number
    7
    7
    Dizziness
         subjects affected / exposed
    4 / 52 (7.69%)
    6 / 51 (11.76%)
         occurrences all number
    5
    7
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    21 / 52 (40.38%)
    24 / 51 (47.06%)
         occurrences all number
    45
    51
    Thrombocytopenia
         subjects affected / exposed
    13 / 52 (25.00%)
    20 / 51 (39.22%)
         occurrences all number
    24
    37
    Anaemia
         subjects affected / exposed
    15 / 52 (28.85%)
    16 / 51 (31.37%)
         occurrences all number
    20
    27
    Leukopenia
         subjects affected / exposed
    3 / 52 (5.77%)
    6 / 51 (11.76%)
         occurrences all number
    3
    8
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    18 / 52 (34.62%)
    24 / 51 (47.06%)
         occurrences all number
    33
    39
    Diarrhoea
         subjects affected / exposed
    21 / 52 (40.38%)
    16 / 51 (31.37%)
         occurrences all number
    41
    19
    Constipation
         subjects affected / exposed
    18 / 52 (34.62%)
    17 / 51 (33.33%)
         occurrences all number
    19
    22
    Vomiting
         subjects affected / exposed
    9 / 52 (17.31%)
    11 / 51 (21.57%)
         occurrences all number
    10
    16
    Dyspepsia
         subjects affected / exposed
    3 / 52 (5.77%)
    5 / 51 (9.80%)
         occurrences all number
    3
    5
    Haemorrhoids
         subjects affected / exposed
    3 / 52 (5.77%)
    5 / 51 (9.80%)
         occurrences all number
    3
    5
    Abdominal pain
         subjects affected / exposed
    2 / 52 (3.85%)
    5 / 51 (9.80%)
         occurrences all number
    2
    5
    Abdominal pain upper
         subjects affected / exposed
    2 / 52 (3.85%)
    4 / 51 (7.84%)
         occurrences all number
    3
    5
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    23 / 52 (44.23%)
    22 / 51 (43.14%)
         occurrences all number
    25
    25
    Rash
         subjects affected / exposed
    4 / 52 (7.69%)
    6 / 51 (11.76%)
         occurrences all number
    4
    8
    Night sweats
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    4
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    6 / 52 (11.54%)
    5 / 51 (9.80%)
         occurrences all number
    8
    8
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 52 (23.08%)
    12 / 51 (23.53%)
         occurrences all number
    19
    22
    Pain in extremity
         subjects affected / exposed
    9 / 52 (17.31%)
    9 / 51 (17.65%)
         occurrences all number
    11
    12
    Myalgia
         subjects affected / exposed
    6 / 52 (11.54%)
    11 / 51 (21.57%)
         occurrences all number
    8
    12
    Muscular weakness
         subjects affected / exposed
    3 / 52 (5.77%)
    6 / 51 (11.76%)
         occurrences all number
    3
    10
    Muscle spasms
         subjects affected / exposed
    5 / 52 (9.62%)
    3 / 51 (5.88%)
         occurrences all number
    6
    4
    Back pain
         subjects affected / exposed
    4 / 52 (7.69%)
    3 / 51 (5.88%)
         occurrences all number
    4
    5
    Bone pain
         subjects affected / exposed
    3 / 52 (5.77%)
    3 / 51 (5.88%)
         occurrences all number
    6
    3
    Musculoskeletal pain
         subjects affected / exposed
    5 / 52 (9.62%)
    2 / 51 (3.92%)
         occurrences all number
    7
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    3
    1
    Neck pain
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    3
    1
    Spinal pain
         subjects affected / exposed
    3 / 52 (5.77%)
    1 / 51 (1.96%)
         occurrences all number
    3
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 52 (7.69%)
    2 / 51 (3.92%)
         occurrences all number
    4
    4
    Rhinitis
         subjects affected / exposed
    4 / 52 (7.69%)
    0 / 51 (0.00%)
         occurrences all number
    7
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 52 (3.85%)
    4 / 51 (7.84%)
         occurrences all number
    2
    5
    Urinary tract infection
         subjects affected / exposed
    3 / 52 (5.77%)
    2 / 51 (3.92%)
         occurrences all number
    5
    2
    Pneumonia
         subjects affected / exposed
    4 / 52 (7.69%)
    1 / 51 (1.96%)
         occurrences all number
    4
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    20 / 52 (38.46%)
    17 / 51 (33.33%)
         occurrences all number
    30
    25
    Dehydration
         subjects affected / exposed
    6 / 52 (11.54%)
    4 / 51 (7.84%)
         occurrences all number
    11
    9
    Hypokalaemia
         subjects affected / exposed
    4 / 52 (7.69%)
    6 / 51 (11.76%)
         occurrences all number
    9
    13
    Hypomagnesaemia
         subjects affected / exposed
    5 / 52 (9.62%)
    4 / 51 (7.84%)
         occurrences all number
    14
    7
    Hyponatraemia
         subjects affected / exposed
    2 / 52 (3.85%)
    6 / 51 (11.76%)
         occurrences all number
    3
    7
    Hyperglycaemia
         subjects affected / exposed
    0 / 52 (0.00%)
    3 / 51 (5.88%)
         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
    17 Sep 2012
    This amendment included study conduct modifications arising from the updated safety experience.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    06 Jun 2013
    The protocol specified primary analysis conducted after the occurrence of approximately 60 PFS events demonstrated no evidence of efficacy with the addition of MEGF0444A to the reference regimen in participants with NSCLC and subsequently the study was terminated by the sponsors.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated because of lack of efficacy of study drug in participants with NSCLC.
    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-Fri May 02 07:29:04 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA