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    Clinical Trial Results:
    A PHASE II, OPEN-LABEL, RANDOMIZED STUDY OF MEHD7945A VERSUS CETUXIMAB IN PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK WHO HAVE PROGRESSED DURING OR FOLLOWING PLATINUM BASED CHEMOTHERAPY

    Summary
    EudraCT number
    		 2011-005539-22
    Trial protocol
    		 BE   DE   GB   ES   HU   IT   BG  
    Global end of trial date
    22 Jun 2015

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

    Trial information

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    Trial identification
    Sponsor protocol code
    GO28076
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01577173
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, 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
    22 Jun 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jun 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    • To evaluate the efficacy, as measured by progression free survival (PFS), of MEHD7945A (administered every 2 weeks) versus cetuximab (administered weekly) in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) • To evaluate the efficacy, as measured by PFS, of MEHD7945A (administered every 2 weeks) versus cetuximab (administered weekly) in subjects with R/M SCCHN whose tumors express high levels of heregulin (HRG)
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Jul 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Bulgaria: 7
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Romania: 21
    Country: Number of subjects enrolled
    United States: 33
    Worldwide total number of subjects
    120
    EEA total number of subjects
    77
    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)
    72
    From 65 to 84 years
    48
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 121 subjects were randomized to treatment in the study. However, 1 subject received no study treatment; therefore 120 subjects were enrolled and received at least 1 dose of study treatment.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 MEHD7945A
    Arm description
    		 Subjects with R/M SCCHN who had progressed during or following platinum-based chemotherapy received MEHD7945A 1100 milligrams (mg) as an intravenous (IV) infusion every 2 weeks until disease progression or intolerable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEHD7945A
    Investigational medicinal product code
    Other name
    Duligotuzumab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received MEHD7945A 1100 mg as an IV infusion every 2 weeks.

    Arm title
    		 Cetuximab
    Arm description
    		 Subjects with R/M SCCHN who had progressed during or following platinum-based chemotherapy received cetuximab 400 milligrams per metre squared (mg/m^2) as an IV infusion for a loaded dose followed by cetuximab 250 mg/m^2 as an IV infusion once weekly until disease progression or intolerable toxicity.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Erbitux
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received cetuximab 400 mg/m^2 as a loaded dose followed by cetuximab 250 mg/m^2 weekly.

    Arm title
    		 Cetuximab then MEHD7945A
    Arm description
    		 Subjects with disease progression on the cetuximab arm could receive MEHD7945A upon confirmation of progressive disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEHD7945A
    Investigational medicinal product code
    Other name
    Duligotuzumab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received MEHD7945A 1100 mg as an IV infusion every 2 weeks after having confirmed progressive disease on cetuximab therapy.

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Erbitux
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received cetuximab 400 mg/m^2 as a loaded dose followed by cetuximab 250 mg/m^2 weekly.

    Number of subjects in period 1
    		MEHD7945A Cetuximab Cetuximab then MEHD7945A
    Started
    59
    37
    24
    Completed
    0
    0
    0
    Not completed
    59
    37
    24
         Death
    44
    30
    17
         Study terminated by sponsor
    7
    7
    5
         Lost to follow-up
    5
    -
    1
         Withdrawal by subject
    3
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 -

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 120 120
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.8 ( 10.1 ) -
    Gender categorical
    Units: Subjects
        Female
    		 19 19
        Male
    		 101 101

    End points

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    End points reporting groups
    Reporting group title
    MEHD7945A
    Reporting group description
    		 Subjects with R/M SCCHN who had progressed during or following platinum-based chemotherapy received MEHD7945A 1100 milligrams (mg) as an intravenous (IV) infusion every 2 weeks until disease progression or intolerable toxicity.

    Reporting group title
    Cetuximab
    Reporting group description
    		 Subjects with R/M SCCHN who had progressed during or following platinum-based chemotherapy received cetuximab 400 milligrams per metre squared (mg/m^2) as an IV infusion for a loaded dose followed by cetuximab 250 mg/m^2 as an IV infusion once weekly until disease progression or intolerable toxicity.

    Reporting group title
    Cetuximab then MEHD7945A
    Reporting group description
    		 Subjects with disease progression on the cetuximab arm could receive MEHD7945A upon confirmation of progressive disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    Subject analysis set title
    Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects randomized to cetuximab who did not cross-over, plus pre-crossover data for subjects randomized to cetuximab who crossed over to MEHD7945A.

    Subject analysis set title
    MEHD7945A, plus Cetuximab then MEHD7945A (Post)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects randomized to MEHD7945A, plus post-crossover data for subjects randomized to cetuximab who crossed over to MEHD7945A.

    Subject analysis set title
    Cetuximab, then MEHD7945A (Post)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Post-crossover data for subjects randomised to cetuximab who crossed over to MEHD7945A.

    Primary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS) [1] [2]
    End point description
    PFS was defined as the time from randomisation to documented disease progression assessed by the investigator using RECIST v1.1 or death from any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diametre of target lesions, the appearance of new lesions and increase of at least 5 millimetre (mm) in the sum of diametres of target lesions. All randomised subjects.
    End point type
    Primary
    End point timeframe
    From the time of randomisation until disease progression or death (approximately 3 years)
    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: Only descriptive data was planned to be reported.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: months
        median (confidence interval 90%)
    4.21 (2.79 to 4.67)
    4.01 (2.96 to 4.99)
    No statistical analyses for this end point

    Primary: PFS in Subjects whose Tumors Express High Levels of Heregulin

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    End point title
    		 PFS in Subjects whose Tumors Express High Levels of Heregulin [3] [4]
    End point description
    PFS was defined as the time from randomisation to documented disease progression assessed by the investigator using RECIST v1.1 or death from any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diametre of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diametres of target lesions. All randomised subjects and whose tumors expressed high levels of heregulin.
    End point type
    Primary
    End point timeframe
    From the time of randomisation until disease progression or death (approximately 3 years)
    Notes
    [3] - 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: Only descriptive data was planned to be reported.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    26
    28
    Units: months
        median (confidence interval 90%)
    2.79 (2.2 to 4.21)
    5.54 (4.01 to 7.66)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with an Objective Response

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    End point title
    		 Percentage of Subjects with an Objective Response [5]
    End point description
    Objective response was defined as a complete response (CR) or a partial response (PR) according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >=30% decrease under baseline of the sum of diametres of all target lesions. All randomised subjects.
    End point type
    Secondary
    End point timeframe
    Approximately 3 years
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: Percentage of Subjects
        number (confidence interval 90%)
    11.9 (6.35 to 20.74)
    14.5 (8.3 to 23.94)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Disease Control

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    End point title
    		 Percentage of Subjects with Disease Control [6]
    End point description
    Disease control was defined as a CR, PR, or stable disease (SD) according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as at >=30% decrease under baseline of the sum of diametres of all target lesions. SD was defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. All randomised subjects.
    End point type
    Secondary
    End point timeframe
    Approximately 3 years
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: Percentage of Subjects
        number (confidence interval 90%)
    76.3 (65.81 to 84.71)
    61.3 (50.7 to 71.57)
    No statistical analyses for this end point

    Secondary: Duration of Objective Response

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    End point title
    		 Duration of Objective Response [7]
    End point description
    Duration of objective response was defined as the time from the first occurrence of a documented objective response to documented disease progression or death from any cause, whichever occurred first. Objective response was defined as a CR or a PR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >=30% decrease under baseline of the sum of diametres of all target lesions. All randomised subjects.
    End point type
    Secondary
    End point timeframe
    From the first occurrence of objective response to disease progression or death from any cause (approximately 3 years)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: months
        median (confidence interval 90%)
    5.42 (3.98 to 5.55)
    4.3 (4.14 to 13.17)
    No statistical analyses for this end point

    Secondary: Time to Disease Progression

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    End point title
    		 Time to Disease Progression [8]
    End point description
    Time to disease progression is defined as the time from randomisation to documented disease progression. Progressive disease was defined as a 20% increase in the sum of the longest diametre of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diametres of target lesions. All randomised subjects.
    End point type
    Secondary
    End point timeframe
    From the time of randomisation until disease progression (approximately 3 years)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: months
        median (confidence interval 90%)
    4.63 (4.07 to 5.49)
    4.07 (3.38 to 5.55)
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival [9]
    End point description
    Overall survival was defined as the time from randomisation to death from any cause. All randomised subjects.
    End point type
    Secondary
    End point timeframe
    From the time of randomisation until death from any cause (approximately 3 years)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab, plus Cetuximab then MEHD7945A (Pre) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre)
    Number of subjects analysed
    59
    62
    Units: months
        median (confidence interval 90%)
    7.16 (5.29 to 9.23)
    8.67 (6.44 to 10.58)
    No statistical analyses for this end point

    Secondary: Number of Subjects with an Adverse Event (AE)

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    End point title
    		 Number of Subjects with an Adverse Event (AE) [10]
    End point description
    An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. The safety population included all subjects who received at least one dose of study medication.
    End point type
    Secondary
    End point timeframe
    Approximately 3 years
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A, Cetuximab, plus Cetuximab then MEHD7945A (Pre), MEHD7945A, plus Cetuximab then MEHD7945A (Post), Cetuximab, then MEHD7945A (Post) only.
    End point values
    		 MEHD7945A Cetuximab, plus Cetuximab then MEHD7945A (Pre) MEHD7945A, plus Cetuximab then MEHD7945A (Post) Cetuximab, then MEHD7945A (Post)
    Number of subjects analysed
    59
    61
    81
    22
    Units: subjects
    58
    59
    79
    21
    No statistical analyses for this end point

    Secondary: Minimum Plasma Concentration of MEHD7945A

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    End point title
    		 Minimum Plasma Concentration of MEHD7945A [11]
    End point description
    Subjects who had at least 1 pharmacokinetic assessment. Here ‘n’ signifies the number of subjects evaluable at specified time points. Here, 99999 indicates geometric mean and geometric co-efficient of variation because more than one-third values are less than reportable.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 8 Day 1
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab then MEHD7945A only.
    End point values
    		 MEHD7945A Cetuximab then MEHD7945A
    Number of subjects analysed
    59
    22
    Units: microgram per milliliter (mcg/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Pre-dose (n=59,21)
    99999 ( 99999 )
    99999 ( 99999 )
        Cycle 2 Day 1 Pre-dose (n=55,21)
    31.6 ( 49.3 )
    49.2 ( 51.5 )
        Cycle 3 Day 1 Pre-dose (n=54,17)
    53.8 ( 48.9 )
    52.9 ( 55 )
        Cycle 4 Day 1 Pre-dose (n=41,12)
    59.5 ( 49 )
    84.9 ( 46.1 )
        Cycle 8 Day 1 Pre-dose (n=13,5)
    51 ( 94.8 )
    115 ( 35.4 )
    No statistical analyses for this end point

    Secondary: Maximum Plasma Concentration of MEHD7945A

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    End point title
    		 Maximum Plasma Concentration of MEHD7945A [12]
    End point description
    Subjects who had at least 1 pharmacokinetic assessment. Here ‘n’ signifies the number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    30 minutes post-dose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 8 Day 1
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab then MEHD7945A only.
    End point values
    		 MEHD7945A Cetuximab then MEHD7945A
    Number of subjects analysed
    59
    22
    Units: microgram per milliliter (ug/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 30 minutes Post-dose (n=58,21)
    279 ( 23.2 )
    195 ( 35.3 )
        Cycle 2 Day 1 30 minutes Post-dose (n=54,21)
    311 ( 27.4 )
    362 ( 25 )
        Cycle 3 Day 1 30 minutes Post-dose (n=53,17)
    356 ( 23.1 )
    402 ( 25.1 )
        Cycle 4 Day 1 30 minutes Post-dose (n=40,12)
    344 ( 28.9 )
    447 ( 30.9 )
        Cycle 8 Day 1 30 minutes Post-dose (n=13,4)
    319 ( 38.6 )
    455 ( 12.3 )
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Positive Anti-MEHD7945A Sample

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    End point title
    		 Percentage of Subjects With a Positive Anti-MEHD7945A Sample [13]
    End point description
    Subjects’ samples were evaluated at baseline and at post-baseline for anti-therapeutic antibodies. The analysis population included any subject with an anti-therapeutic antibody sample at baseline and at least one post-baseline sample.
    End point type
    Secondary
    End point timeframe
    Baseline and any time post baseline (approximately 3 years)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data in the endpoint was planned to be reported for the reporting groups MEHD7945A and Cetuximab then MEHD7945A only.
    End point values
    		 MEHD7945A Cetuximab then MEHD7945A
    Number of subjects analysed
    59
    22
    Units: Percentage of Subjects
    number (not applicable)
        Baseline (n=58,17)
    8.6
    0
        Post-baseline (n=48,22)
    2.1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the randomisation of the first subject to the clinical cutoff date (22JUN2015) (Approximately 3 years)
    Adverse event reporting additional description
    An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. The safety population included all subjects who received at least one dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    All subjects
    Reporting group description
    		 Subjects with R/M SCCHN who had progressed during or following platinum-based chemotherapy received MEHD7945A and cetuximab as documented in the study.

    Serious adverse events
    		 All subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    46 / 120 (38.33%)
         number of deaths (all causes)
    7
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Face oedema
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Performance status decreased
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ulcer
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchiectasis
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    Atrioventricular block
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Epilepsy
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysphagia
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Oral dysaesthesia
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abscess neck
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Lung infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Pneumonia necrotising
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory tract infection
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 120 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    115 / 120 (95.83%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    18
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    20
    Hypotension
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    21
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    17 / 120 (14.17%)
         occurrences all number
    58
    Chest pain
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    14
    Chills
         subjects affected / exposed
    11 / 120 (9.17%)
         occurrences all number
    38
    Fatigue
         subjects affected / exposed
    39 / 120 (32.50%)
         occurrences all number
    132
    Mucosal inflammation
         subjects affected / exposed
    18 / 120 (15.00%)
         occurrences all number
    71
    Oedema peripheral
         subjects affected / exposed
    9 / 120 (7.50%)
         occurrences all number
    27
    Pain
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    28
    Pyrexia
         subjects affected / exposed
    23 / 120 (19.17%)
         occurrences all number
    74
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    22
    Dyspnoea
         subjects affected / exposed
    17 / 120 (14.17%)
         occurrences all number
    51
    Epistaxis
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    27
    Haemoptysis
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    21
    Productive cough
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    15
    Rhinorrhoea
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    12
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    11
    Insomnia
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    15
    Investigations
    Weight decreased
         subjects affected / exposed
    18 / 120 (15.00%)
         occurrences all number
    73
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    13
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    22
    Headache
         subjects affected / exposed
    22 / 120 (18.33%)
         occurrences all number
    90
    Presyncope
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences all number
    8
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 120 (11.67%)
         occurrences all number
    77
    Eye disorders
    Vision blurred
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    11
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    15
    Constipation
         subjects affected / exposed
    17 / 120 (14.17%)
         occurrences all number
    83
    Diarrhoea
         subjects affected / exposed
    46 / 120 (38.33%)
         occurrences all number
    184
    Dry mouth
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    15
    Dyspepsia
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    26
    Dysphagia
         subjects affected / exposed
    9 / 120 (7.50%)
         occurrences all number
    30
    Mouth ulceration
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    18
    Nausea
         subjects affected / exposed
    31 / 120 (25.83%)
         occurrences all number
    163
    Oral pain
         subjects affected / exposed
    6 / 120 (5.00%)
         occurrences all number
    20
    Stomatitis
         subjects affected / exposed
    13 / 120 (10.83%)
         occurrences all number
    44
    Vomiting
         subjects affected / exposed
    25 / 120 (20.83%)
         occurrences all number
    144
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    44
    Dermatitis acneiform
         subjects affected / exposed
    26 / 120 (21.67%)
         occurrences all number
    104
    Dry skin
         subjects affected / exposed
    19 / 120 (15.83%)
         occurrences all number
    62
    Erythema
         subjects affected / exposed
    10 / 120 (8.33%)
         occurrences all number
    56
    Nail discolouration
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences all number
    8
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    7 / 120 (5.83%)
         occurrences all number
    26
    Pruritus
         subjects affected / exposed
    11 / 120 (9.17%)
         occurrences all number
    43
    Rash
         subjects affected / exposed
    37 / 120 (30.83%)
         occurrences all number
    223
    Rash maculo-papular
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    42
    Skin fissures
         subjects affected / exposed
    19 / 120 (15.83%)
         occurrences all number
    74
    Skin ulcer
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    13
    Swelling face
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    20
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    11
    Back pain
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    20
    Muscle spasms
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    15
    Muscular weakness
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    20
    Myalgia
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    25
    Neck pain
         subjects affected / exposed
    10 / 120 (8.33%)
         occurrences all number
    31
    Pain in jaw
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    23
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    5 / 120 (4.17%)
         occurrences all number
    13
    Candida infection
         subjects affected / exposed
    3 / 120 (2.50%)
         occurrences all number
    11
    Conjunctivitis
         subjects affected / exposed
    13 / 120 (10.83%)
         occurrences all number
    66
    Oral candidiasis
         subjects affected / exposed
    4 / 120 (3.33%)
         occurrences all number
    13
    Paronychia
         subjects affected / exposed
    22 / 120 (18.33%)
         occurrences all number
    105
    Pharyngitis
         subjects affected / exposed
    2 / 120 (1.67%)
         occurrences all number
    8
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    21 / 120 (17.50%)
         occurrences all number
    68
    Dehydration
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    25
    Hypokalaemia
         subjects affected / exposed
    16 / 120 (13.33%)
         occurrences all number
    65
    Hypomagnesaemia
         subjects affected / exposed
    29 / 120 (24.17%)
         occurrences all number
    117
    Hypophosphataemia
         subjects affected / exposed
    8 / 120 (6.67%)
         occurrences all number
    29

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Aug 2012
    Study GO28076 had been amended primarily to address comments and recommendations received from study investigators regarding enrollment of patients who have failed platinum-based therapy and are not eligible for local focal therapy as well as reducing the wash-out period required for non-biologic therapies prior to initiating study treatment. Additional changes had been made to ensure enrollment of at least 80 HPV-negative patients and to align the duration of pregnancy prevention with the duration of safety follow-up.
    12 Feb 2013
    Study GO28076 had been amended primarily to update clinical data from the Phase I study, DAF4873g, as of 25 November 2012, including results from QT analyses (see Section 1.2.2) and to add triplicate electrocardiogram (ECG) monitoring for patients treated with MEHD7945A in Arms A and Ax.

    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.
    Study terminated early by Sponsor in Sep. 2014 due to primary analysis indicating primary endpoint of PFS improvement with MEHD47945A over Cetuximab was not met. One subject remained on MEHD7945A at the investigator’s request until June 2015.
    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.

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