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    Clinical Trial Results:
    An open Phase I/II study of immunization with the recMAGE-A3 + AS15 Antigen Specific Cancer Immunotherapeutic in association with dacarbazine in patients with MAGE-A3 positive unresectable and progressive metastatic cutaneous melanoma

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    2008-001918-25
    Trial protocol
    FR   BE  
    Global end of trial date
    17 Nov 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Feb 2016
    First version publication date
    13 Feb 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    111714
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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 May 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Nov 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Nov 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Co-primary objectives of this study were to characterize in the overall population and in the gene signature (GS) subsets: - The safety of MAGE-A3 ASCI study product in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma, with emphasis on any possible toxic effects. - The specific humoral and cellular immune response induced by the MAGE-A3 ASCI study product in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma.
    Protection of trial subjects
    The patients will be observed closely for at least 30 minutes following the administration of treatments, with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    26 May 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    France: 38
    Worldwide total number of subjects
    48
    EEA total number of subjects
    48
    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)
    47
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the patients and signing informed consent forms.

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

    Arms
    Arm title
    MAGE-A3 Group
    Arm description
    Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles
    Arm type
    Experimental

    Investigational medicinal product name
    Other name
    Investigational medicinal product code
    Other name
    recMAGE-A3 recombinant protein + immunological Adjuvant System
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Administration as follows: 12 administrations in Cycle 1, at 3-week intervals (Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31 and 34) and 8 doses of a standard intravenous chemotherapy regimen consisting of dacarbazine and prophylactic anti-emetic medications administered over one hour on Weeks 1, 4, 7, 10, 13, 16, 19 and 22; 4 administrations in Cycle 2, at 6-week intervals (Weeks 38, 44, 50 and 56); 4 administrations in Cycle 3 at 3-month intervals and 4 administrations i at 6-month intervals.

    Investigational medicinal product name
    Darcabazine
    Investigational medicinal product code
    Other name
    Chemotherapy
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    During Cycle 1, 8 doses of a standard intravenous chemotherapy regimen consisting of dacarbazine administered over one hour on Weeks 1, 4, 7, 10, 13, 16, 19 and 22;

    Investigational medicinal product name
    Anti-emetic medication
    Investigational medicinal product code
    Other name
    A serotonin 5-HT3 receptor antagonist (e.g. ondansetron, dolasetron or granisetron)
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administration prior to each course of chemotherapy, according to standard procedures at the site.

    Investigational medicinal product name
    Anti-emetic medication
    Investigational medicinal product code
    Other name
    A serotonin 5-HT3 receptor antagonist (e.g. ondansetron, dolasetron or granisetron)
    Pharmaceutical forms
    Pillules
    Routes of administration
    Oral use
    Dosage and administration details
    Administration at 6 hours after each course of chemotherapy, according to standard procedures at the site.

    Number of subjects in period 1
    MAGE-A3 Group
    Started
    48
    Completed
    1
    Not completed
    47
         Death
    28
         Ongoing (unknown completion status)
    11
         Others
    6
         Lost to follow-up
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MAGE-A3 Group
    Reporting group description
    Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles

    Reporting group values
    MAGE-A3 Group Total
    Number of subjects
    48 48
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    55.44 ± 15.99 -
    Gender categorical
    Units: Subjects
        Female
    21 21
        Male
    27 27
    Subject analysis sets

    Subject analysis set title
    GS+ Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Subject analysis set title
    GS- Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Subject analysis set title
    Unknown GS Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients with unknown status as regards GS signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Subject analysis sets values
    GS+ Group GS- Group Unknown GS Group
    Number of subjects
    32
    15
    1
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.8 ± 15.4
    56.1 ± 18
    66 ± 0
    Gender categorical
    Units: Subjects
        Female
    16
    5
    0
        Male
    16
    10
    1

    End points

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    End points reporting groups
    Reporting group title
    MAGE-A3 Group
    Reporting group description
    Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles

    Subject analysis set title
    GS+ Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Subject analysis set title
    GS- Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Subject analysis set title
    Unknown GS Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subset of patients with unknown status as regards GS signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

    Primary: Number of patients reported with unsolicited adverse events (AEs) that were causally related to treatment administration by maximum grade.

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    End point title
    Number of patients reported with unsolicited adverse events (AEs) that were causally related to treatment administration by maximum grade. [1]
    End point description
    The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the treatment.
    End point type
    Primary
    End point timeframe
    Within the 31-day (Days 0-30) post-administration period.
    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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Patients
        Any event, Grade 3
    3
        Any event, Grade 4
    1
        Any Blood and lymphatic system disorders, Grade 3
    1
        Any Blood and lymphatic system disorders, Grade 4
    1
        Anaemia, Grade 3
    0
        Anaemia, Grade 4
    0
        Lymphopenia, Grade 3
    0
        Lymphopenia, Grade 4
    0
        Neutropenia, Grade 3
    1
        Neutropenia, Grade 4
    1
        Thrombocytopenia, Grade 3
    0
        Thrombocytopenia, Grade 4
    1
        Any Cardiac disorders, Grade 3
    0
        Any Cardiac disorders, Grade 4
    0
        Tachycardia, Grade 3
    0
        Tachycardia, Grade 4
    0
        Any Gastrointestinal disorders, Grade 3
    0
        Any Gastrointestinal disorders, Grade 4
    0
        Constipation, Grade 3
    0
        Constipation, Grade 4
    0
        Diarrhoea, Grade 3
    0
        Diarrhoea, Grade 4
    0
        Dyspepsia, Grade 3
    0
        Dyspepsia, Grade 4
    0
        Nausea, Grade 3
    0
        Nausea, Grade 4
    0
        Paraesthesia oral, Grade 3
    0
        Paraesthesia oral, Grade 4
    0
        Vomiting, Grade 3
    0
        Vomiting, Grade 4
    0
        Any Gen. disord. and adm. site conditions, Grade 3
    1
        Any Gen. disord. and adm. site conditions, Grade 4
    0
        Asthenia, Grade 3
    0
        Asthenia, Grade 4
    0
        Chills, Grade 3
    0
        Chills, Grade 4
    0
        Fatigue, Grade 3
    0
        Fatigue, Grade 4
    0
        Influenza like illness, Grade 3
    0
        Influenza like illness, Grade 4
    0
        Injection site erythema, Grade 3
    0
        Injection site erythema, Grade 4
    0
        Injection site inflammation, Grade 3
    1
        Injection site inflammation, Grade 4
    0
        Injection site oedema, Grade 3
    0
        Injection site oedema, Grade 4
    0
        Injection site pain, Grade 3
    0
        Injection site pain, Grade 4
    0
        Injection site reaction, Grade 3
    0
        Injection site reaction, Grade 4
    0
        Mucosal dryness, Grade 3
    0
        Mucosal dryness, Grade 4
    0
        Oedema peripheral, Grade 3
    0
        Oedema peripheral, Grade 4
    0
        Pyrexia, Grade 3
    0
        Pyrexia, Grade 4
    0
        Any Investigations, Grade 3
    1
        Any Investigations, Grade 4
    0
        Haemoglobin decreased, Grade 3
    1
        Haemoglobin decreased, Grade 4
    0
        Any Metabolism and nutrition disorders, Grade 3
    0
        Any Metabolism and nutrition disorders, Grade 4
    0
        Decreased appetite, Grade 3
    0
        Decreased appetite, Grade 4
    0
        Any Musculoskeletal and conn. Tiss. Diso., Grade 3
    0
        Any Musculoskeletal and conn. Tiss. Diso., Grade 4
    0
        Arthralgia, Grade 3
    0
        Arthralgia, Grade 4
    0
        Myalgia, Grade 3
    0
        Myalgia, Grade 4
    0
        Pain in extremity, Grade 3
    0
        Pain in extremity, Grade 4
    0
        Any Nervous system disorders, Grade 3
    0
        Any Nervous system disorders, Grade 4
    0
        Burning sensation, Grade 3
    0
        Burning sensation, Grade 4
    0
        Headache, Grade 3
    0
        Headache, Grade 4
    0
        Paraesthesia, Grade 3
    0
        Paraesthesia, Grade 4
    0
        Presyncope, Grade 3
    0
        Presyncope, Grade 4
    0
        Any Psychiatric disorders, Grade 3
    0
        Any Psychiatric disorders, Grade 4
    0
        Insomnia, Grade 3
    0
        Insomnia, Grade 4
    0
        Any Resp., thoracic and mediastinal. dis., Grade 3
    0
        Any Resp., thoracic and mediastinal. dis., Grade 4
    0
        Rhinitis allergic, Grade 3
    0
        Rhinitis allergic, Grade 4
    0
        Any Skin and subcutaneous tissue disorder, Grade 3
    0
        Any Skin and subcutaneous tissue disorder, Grade 4
    0
        Alopecia, Grade 3
    0
        Alopecia, Grade 4
    0
        Eczema, Grade 3
    0
        Eczema, Grade 4
    0
        Photosensitivity reaction, Grade 3
    0
        Photosensitivity reaction, Grade 4
    0
        Pruritus, Grade 3
    0
        Pruritus, Grade 4
    0
        Any Vascular disorders, Grade 3
    0
        Any Vascular disorders, Grade 4
    0
        Hypotension, Grade 3
    0
        Hypotension, Grade 4
    0
    No statistical analyses for this end point

    Primary: Number of patients reported with serious adverse events (SAEs)

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    End point title
    Number of patients reported with serious adverse events (SAEs) [2]
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.
    End point type
    Primary
    End point timeframe
    During the entire study period.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Patients
        Any SAEs
    10
    No statistical analyses for this end point

    Primary: Number of seroconverted patients for anti-MAGE-A3

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    End point title
    Number of seroconverted patients for anti-MAGE-A3 [3]
    End point description
    Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27.
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    1
    Units: Patients
        Anti-MAGE-A3, W13
    28
    19
    8
    1
    No statistical analyses for this end point

    Primary: Anti-MAGE-A3 antibody concentrations

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    End point title
    Anti-MAGE-A3 antibody concentrations [4]
    End point description
    Anti-MAGE-A3 antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL)
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group
    Number of subjects analysed
    28
    19
    8
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-MAGE-A3, W13
    2778.7 (1638.3 to 4712.8)
    2650.8 (1425.5 to 4929.2)
    4046.9 (1206.5 to 13574.7)
    No statistical analyses for this end point

    Primary: Number of patients with treatment response for anti-MAGE-A3 antibodies

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    End point title
    Number of patients with treatment response for anti-MAGE-A3 antibodies [5]
    End point description
    Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [5] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    1
    Units: Patients
        Anti-MAGE-A3, W13
    28
    19
    8
    1
    No statistical analyses for this end point

    Primary: Anti-MAGE-A3 antibody concentrations (CMI)

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    End point title
    Anti-MAGE-A3 antibody concentrations (CMI) [6]
    End point description
    Analysis of MAGE-A3 cellular response was not performed.
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [6] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    1
    Units: Patients
        Anti-MAGE-A3, W13
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of seroconverted patients for protein D

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    End point title
    Number of seroconverted patients for protein D [7]
    End point description
    Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-PD antibody concentrations ≥ 100 EL.U/mL
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [7] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    19
    Units: Patients
        Anti-PD, W13
    28
    19
    8
    1
    No statistical analyses for this end point

    Primary: Concentrations of antibodies against protein D (Anti-PD)

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    End point title
    Concentrations of antibodies against protein D (Anti-PD) [8]
    End point description
    Anti-PD antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL). “0”, “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [8] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    1
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PD, W13
    9979.6 (6470 to 15393)
    10437 (5932.8 to 18361)
    10853.6 (4823.4 to 24422.7)
    2176 (-9999 to 9999)
    No statistical analyses for this end point

    Primary: Number of patients with treatment response for anti-PD

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    End point title
    Number of patients with treatment response for anti-PD [9]
    End point description
    Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 100 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration
    End point type
    Primary
    End point timeframe
    Post Dose 4 at Week 13 (W13).
    Notes
    [9] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    28
    19
    8
    1
    Units: Patients
        Anti-PD, W13
    28
    19
    8
    1
    No statistical analyses for this end point

    Secondary: Percentage (%) of patients with objective tumor response (OR) to MAGE-A3 ASCI study treatment

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    End point title
    Percentage (%) of patients with objective tumor response (OR) to MAGE-A3 ASCI study treatment
    End point description
    Response assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs), and followed up until disease progression. Up to 5 MLs per organ & 10 in total were identified as TLs and measured at baseline, selected based on size (those with the longest diameter [LD]) and measurability; a sum of LDs for all TLs was calculated and reported as baseline sum LD, which was used to characterize objective tumor response (OR), OR being defined as either complete response (CR) and/or partial response (PR) post MAGE-A3 ASCI treatment. After identification, MLs and TLs were assessed as regards CR and PR definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. For RECIST criteria details, refer to Therasse P, et al., J Nat Cancer Inst 2000; 92: 205–216).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    48
    32
    15
    1
    Units: % of patients
        OR
    4
    4
    0
    0
        CR
    1
    1
    0
    0
        PR
    3
    3
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage (%) of patients with stable disease (SD) response to MAGE-A3 ASCI study treatment

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    End point title
    Percentage (%) of patients with stable disease (SD) response to MAGE-A3 ASCI study treatment
    End point description
    Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. TLs and NTLs were assessed as regards matching or not SD-related definitions, 1) SD definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (see above for reference) for TLs >= 20 mm and TLs both >= and < 20 mm, e. a. a) for TLs: SD = Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since treatment start. and b) for NTLs: SD = Persistence of one or more NTL; 2) following below criteria for TLs < 20mm e. a. a) for TLs: PR/SD = Neither sufficient shrinkage to qualify for CR nor sufficient increase, to qualify for PD taking as references the smallest sum LD since treatment start, and b) for NTLs: PR/SD = Persistence of one or more NTL.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    48
    32
    15
    1
    Units: % of patients
        SD
    5
    4
    0
    1
        SD/PR
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Duration of stable disease (SD) response to MAGE-A3 ASCI study treatment

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    End point title
    Duration of stable disease (SD) response to MAGE-A3 ASCI study treatment
    End point description
    Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. Stable disease was defined as follows: 1) In case of target lesions (TL) greater than or equal to (≥) 20 mm: neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as references the sum of Longest Diameter (LD) of TL recorded previously but not necessarily at baseline; 2) In case of TL both less than 20 mm and ≥ 20 mm: Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since the start of the treatment. The minimal time interval required between 2 measurements for determination of SD was at least 12 weeks. “-9999” & “9999” are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
    End point values
    GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    6
    2
    1
    Units: Time expressed in months
    median (confidence interval 95%)
        SD Duration
    5.6 (5.3 to 8.3)
    7.7 (7.2 to 8.3)
    5.1 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage (%) of patients with mixed response (MxR) to MAGE-A3 ASCI study treatment

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    End point title
    Percentage (%) of patients with mixed response (MxR) to MAGE-A3 ASCI study treatment
    End point description
    Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. MLs were assessed as regards matching below MxR definitions. In case of evaluability per RECIST: a) MxR Type 1= at least (a.l.) 30% decrease in LD in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL, and = SD/PR with new lesion. In case of non-evaluability per RECIST: a) MxR Type 1 = a clear decrease in diameters occurring in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of (baseline) TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL = SD/PR with new lesion.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    48
    32
    15
    1
    Units: % of patients
        MxR: SD/PR with new lesion
    10
    6
    4
    0
        MxR: SD/PD with target lesion regression
    1
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Time to treatment failure (TTF), by Gene Signature

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    End point title
    Time to treatment failure (TTF), by Gene Signature
    End point description
    TTF was defined as withdrawal from treatment with the MAGE-A3 ASCI study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression or death
    End point values
    GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    32
    15
    1
    Units: Time expressed in months
    median (confidence interval 95%)
        TTF
    2.8 (2.1 to 4.9)
    2.3 (2.1 to 3)
    4.3 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) for the overall population

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    End point title
    Progression-free survival (PFS) for the overall population
    End point description
    PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression or death
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Time expressed in months
    median (confidence interval 95%)
        PFS
    2.8 (2.8 to 3)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) by Gene Signature

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    End point title
    Progression-free survival (PFS) by Gene Signature
    End point description
    PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of disease progression or death
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    48
    32
    15
    1
    Units: Time expressed in months
    median (confidence interval 95%)
        PFS
    2.8 (2.8 to 3)
    2.8 (2.8 to 3.4)
    2.8 (2.2 to 3.3)
    5.1 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) after slow progressive disease (SPD) by Gene Signature

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    End point title
    Progression-free survival (PFS) after slow progressive disease (SPD) by Gene Signature
    End point description
    PFS after initial SPD was defined and calculated as the time from the time point at which the disease was the most advanced during the treatment to either a new progression of the disease or the date to death, whichever occurred first as another secondary outcome of this study. In that case, the largest diameter during the course of treatment was to be used as reference measurement. This outcome was defined to take into account the delay to induce an active immune response and the strict rules set up in this study to allow pursuing investigational treatment in case of SPD. PFS after SPD analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at 1st report of new disease progression or death, largest diameter reported for lesions assessed during the course of treatment being used as reference measurement.
    End point values
    GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    32
    15
    1
    Units: Time expressed in months
    median (confidence interval 95%)
        PFS after SPD
    2.8 (2.8 to 5.3)
    2.8 (2.2 to 3.3)
    5.1 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Overall survival (OS) by Gene Signature

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    End point title
    Overall survival (OS) by Gene Signature
    End point description
    OS was defined as the time from first treatment to the date of death. OS analysis was performed using the non-parametric Kaplan-Meier method. “0”, “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing.
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death
    End point values
    MAGE-A3 Group GS+ Group GS- Group Unknown GS Group
    Number of subjects analysed
    48
    32
    15
    1
    Units: Time expressed in months
    median (confidence interval 95%)
        OS
    9.4 (5.8 to 15.8)
    11.4 (7.3 to 17.1)
    5.3 (3.3 to 10.5)
    0 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Alanine aminotransferase (ALT) values by maximum grade

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    End point title
    Number of patients with abnormal Alanine aminotransferase (ALT) values by maximum grade
    End point description
    The status of each patient as regards ALT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        ALT - SCR G0; SE G0
    34
        ALT - SCR G0; SE G1
    3
        ALT - SCR G0; SE G2
    1
        ALT - SCR G0; SE G3
    1
        ALT - SCR G0; SE G4
    0
        ALT - SCR G0; SE UNK
    1
        ALT - SCR G1; SE G0
    3
        ALT - SCR G1; SE G1
    2
        ALT - SCR G1; SE G2
    1
        ALT - SCR G1; SE G3
    0
        ALT - SCR G1; SE G4
    0
        ALT - SCR G1; SE UNK
    1
        ALT - SCR G2; SE G0
    0
        ALT - SCR G2; SE G1
    1
        ALT - SCR G2; SE G2
    0
        ALT - SCR G2; SE G3
    0
        ALT - SCR G2; SE G4
    0
        ALT - SCR G2; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Aspartate aminotransferase (AST) values by maximum grade

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    End point title
    Number of patients with abnormal Aspartate aminotransferase (AST) values by maximum grade
    End point description
    The status of each patient as regards AST laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        AST - SCR G0; SE G0
    36
        AST - SCR G0; SE G1
    2
        AST - SCR G0; SE G2
    1
        AST - SCR G0; SE G3
    0
        AST - SCR G0; SE G4
    1
        AST - SCR G0; SE UNK
    1
        AST - SCR G1; SE G0
    2
        AST - SCR G1; SE G1
    3
        AST - SCR G1; SE G2
    1
        AST - SCR G1; SE G3
    0
        AST - SCR G1; SE G4
    0
        AST - SCR G1; SE UNK
    1
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Alkaline Phosphatase (ALK) values by maximum grade

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    End point title
    Number of patients with abnormal Alkaline Phosphatase (ALK) values by maximum grade
    End point description
    The status of each patient as regards ALK laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        ALK - SCR G0; SE G0
    31
        ALK - SCR G0; SE G1
    11
        ALK - SCR G0; SE G2
    0
        ALK - SCR G0; SE G3
    0
        ALK - SCR G0; SE G4
    0
        ALK - SCR G0; SE UNK
    1
        ALK - SCR G1; SE G0
    1
        ALK - SCR G1; SE G1
    3
        ALK - SCR G1; SE G2
    0
        ALK - SCR G1; SE G3
    0
        ALK - SCR G1; SE G4
    0
        ALK - SCR G1; SE UNK
    1
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Bilirubine (BIL) values by maximum grade

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    End point title
    Number of patients with abnormal Bilirubine (BIL) values by maximum grade
    End point description
    The status of each patient as regards BIL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK) and Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        BIL - SCR UNK; SE G0
    1
        BIL - SCR UNK; SE G1
    0
        BIL - SCR UNK; SE G2
    0
        BIL - SCR UNK; SE G3
    0
        BIL - SCR UNK; SE G4
    0
        BIL - SCR UNK; SE UNK
    0
        BIL - SCR G0; SE G0
    39
        BIL - SCR G0; SE G1
    3
        BIL - SCR G0; SE G2
    0
        BIL - SCR G0; SE G3
    0
        BIL - SCR G0; SE G4
    0
        BIL - SCR G0; SE UNK
    5
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Creatinine (CREA) values by maximum grade

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    End point title
    Number of patients with abnormal Creatinine (CREA) values by maximum grade
    End point description
    The status of each patient as regards CREA laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        CREA - SCR G0; SE G0
    40
        CREA - SCR G0; SE G1
    4
        CREA - SCR G0; SE G2
    1
        CREA - SCR G0; SE G3
    0
        CREA - SCR G0; SE G4
    1
        CREA - SCR G0; SE UNK
    2
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal gamma-glutamyl transpeptidase (GGT) values by maximum grade

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    End point title
    Number of patients with abnormal gamma-glutamyl transpeptidase (GGT) values by maximum grade
    End point description
    The status of each patient as regards GGT laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G3. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        GGT - SCR G0; SE G0
    20
        GGT - SCR G0; SE G1
    11
        GGT - SCR G0; SE G2
    4
        GGT - SCR G0; SE G3
    0
        GGT - SCR G0; SE G4
    0
        GGT - SCR G0; SE UNK
    2
        GGT - SCR G1; SE G0
    2
        GGT - SCR G1; SE G1
    2
        GGT - SCR G1; SE G2
    0
        GGT - SCR G1; SE G3
    0
        GGT - SCR G1; SE G4
    0
        GGT - SCR G1; SE UNK
    0
        GGT - SCR G3; SE G0
    0
        GGT - SCR G3; SE G1
    0
        GGT - SCR G3; SE G2
    0
        GGT - SCR G3; SE G3
    1
        GGT - SCR G3; SE G4
    0
        GGT - SCR G3; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Hemoglobin (HGB) values by maximum grade

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    End point title
    Number of patients with abnormal Hemoglobin (HGB) values by maximum grade
    End point description
    The status of each patient as regards HGB laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        HGB - SCR G0; SE G0
    22
        HGB - SCR G0; SE G1
    14
        HGB - SCR G0; SE G2
    5
        HGB - SCR G0; SE G3
    1
        HGB - SCR G0; SE G4
    0
        HGB - SCR G0; SE UNK
    2
        HGB - SCR G1; SE G0
    2
        HGB - SCR G1; SE G1
    2
        HGB - SCR G1; SE G2
    0
        HGB - SCR G1; SE G3
    0
        HGB - SCR G1; SE G4
    0
        HGB - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Hypercalcemia (HCA) values by maximum grade

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    End point title
    Number of patients with abnormal Hypercalcemia (HCA) values by maximum grade
    End point description
    The status of each patient as regards HCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        HCA - SCR UNK; SE G0
    2
        HCA - SCR UNK; SE G1
    1
        HCA - SCR UNK; SE G2
    0
        HCA - SCR UNK; SE G3
    0
        HCA - SCR UNK; SE G4
    0
        HCA - SCR UNK; SE UNK
    0
        HCA - SCR G0; SE G0
    37
        HCA - SCR G0; SE G1
    0
        HCA - SCR G0; SE G2
    0
        HCA - SCR G0; SE G3
    0
        HCA - SCR G0; SE G4
    0
        HCA - SCR G0; SE UNK
    6
        HCA - SCR G1; SE G1
    1
        HCA - SCR G1; SE G2
    1
        HCA - SCR G1; SE G3
    0
        HCA - SCR G1; SE G4
    0
        HCA - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Hyperkalemia (HKA) values by maximum grade

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    End point title
    Number of patients with abnormal Hyperkalemia (HKA) values by maximum grade
    End point description
    The status of each patient as regards HKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        HKA - SCR G0; SE G0
    42
        HKA - SCR G0; SE G1
    2
        HKA - SCR G0; SE G2
    0
        HKA - SCR G0; SE G3
    0
        HKA - SCR G0; SE G4
    0
        HKA - SCR G0; SE UNK
    1
        HKA - SCR G1; SE G0
    1
        HKA - SCR G1; SE G1
    0
        HKA - SCR G1; SE G2
    0
        HKA - SCR G1; SE G3
    0
        HKA - SCR G1; SE G4
    0
        HKA - SCR G1; SE UNK
    1
        HKA - SCR G2; SE G0
    1
        HKA - SCR G2; SE G1
    0
        HKA - SCR G2; SE G2
    0
        HKA - SCR G2; SE G3
    0
        HKA - SCR G2; SE G4
    0
        HKA - SCR G2; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Hypernatremia (HNA) values by maximum grade

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    End point title
    Number of patients with abnormal Hypernatremia (HNA) values by maximum grade
    End point description
    The status of each patient as regards HNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        HNA - SCR G0; SE G0
    44
        HNA - SCR G0; SE G1
    0
        HNA - SCR G0; SE G2
    0
        HNA - SCR G0; SE G3
    0
        HNA - SCR G0; SE G4
    0
        HNA - SCR G0; SE UNK
    2
        HNA - SCR G1; SE G0
    2
        HNA - SCR G1; SE G1
    0
        HNA - SCR G1; SE G2
    0
        HNA - SCR G1; SE G3
    0
        HNA - SCR G1; SE G4
    0
        HNA - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal hypoalbuminemia(hAL) values by maximum grade

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    End point title
    Number of patients with abnormal hypoalbuminemia(hAL) values by maximum grade
    End point description
    The status of each patient as regards hAL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        hAL - SCR UNK; SE G0
    1
        hAL - SCR UNK; SE G1
    0
        hAL - SCR UNK; SE G2
    1
        hAL - SCR UNK; SE G3
    0
        hAL - SCR UNK; SE G4
    0
        hAL - SCR UNK; SE UNK
    1
        hAL - SCR G0; SE G0
    26
        hAL - SCR G0; SE G1
    4
        hAL - SCR G0; SE G2
    2
        hAL - SCR G0; SE G3
    0
        hAL - SCR G0; SE G4
    0
        hAL - SCR G0; SE UNK
    4
        hAL - SCR G1; SE G1
    4
        hAL - SCR G1; SE G2
    3
        hAL - SCR G1; SE G3
    0
        hAL - SCR G1; SE G4
    0
        hAL - SCR G1; SE UNK
    2
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal hypocalcemia(hCA) values by maximum grade

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    End point title
    Number of patients with abnormal hypocalcemia(hCA) values by maximum grade
    End point description
    The status of each patient as regards hCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        hCA - SCR UNK; SE G0
    1
        hCA - SCR UNK; SE G1
    1
        hCA - SCR UNK; SE G2
    0
        hCA - SCR UNK; SE G3
    0
        hCA - SCR UNK; SE G4
    1
        hCA - SCR UNK; SE UNK
    0
        hCA - SCR G0; SE G0
    27
        hCA - SCR G0; SE G1
    7
        hCA - SCR G0; SE G2
    0
        hCA - SCR G0; SE G3
    0
        hCA - SCR G0; SE G4
    0
        hCA - SCR G0; SE UNK
    5
        hCA - SCR G1; SE G0
    0
        hCA - SCR G1; SE G1
    5
        hCA - SCR G1; SE G2
    0
        hCA - SCR G1; SE G3
    0
        hCA - SCR G1; SE G4
    0
        hCA - SCR G1; SE UNK
    1
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal hypokalemia (hKA) values by maximum grade

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    End point title
    Number of patients with abnormal hypokalemia (hKA) values by maximum grade
    End point description
    The status of each patient as regards hKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        hKA - SCR G0; SE G0
    42
        hKA - SCR G0; SE G1
    1
        hKA - SCR G0; SE G2
    0
        hKA - SCR G0; SE G3
    0
        hKA - SCR G0; SE G4
    0
        hKA - SCR G0; SE UNK
    1
        hKA - SCR G1; SE G0
    3
        hKA - SCR G1; SE G1
    0
        hKA - SCR G1; SE G2
    0
        hKA - SCR G1; SE G3
    0
        hKA - SCR G1; SE G4
    0
        hKA - SCR G1; SE UNK
    1
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal hyponatremia (hNA) values by maximum grade

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    End point title
    Number of patients with abnormal hyponatremia (hNA) values by maximum grade
    End point description
    The status of each patient as regards hNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        hNA - SCR G0; SE G0
    33
        hNA - SCR G0; SE G1
    10
        hNA - SCR G0; SE G2
    0
        hNA - SCR G0; SE G3
    1
        hNA - SCR G0; SE G4
    0
        hNA - SCR G0; SE UNK
    2
        hNA - SCR G1; SE G0
    1
        hNA - SCR G1; SE G1
    1
        hNA - SCR G1; SE G2
    0
        hNA - SCR G1; SE G3
    0
        hNA - SCR G1; SE G4
    0
        hNA - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Leukocytes (LEU) values by maximum grade

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    End point title
    Number of patients with abnormal Leukocytes (LEU) values by maximum grade
    End point description
    The status of each patient as regards LEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        LEU - SCR G0; SE G0
    37
        LEU - SCR G0; SE G1
    6
        LEU - SCR G0; SE G2
    0
        LEU - SCR G0; SE G3
    1
        LEU - SCR G0; SE G4
    0
        LEU - SCR G0; SE UNK
    2
        LEU - SCR G1; SE G0
    0
        LEU - SCR G1; SE G1
    1
        LEU - SCR G1; SE G2
    1
        LEU - SCR G1; SE G3
    0
        LEU - SCR G1; SE G4
    0
        LEU - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Lymphopenia (LYM) values by maximum grade

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    End point title
    Number of patients with abnormal Lymphopenia (LYM) values by maximum grade
    End point description
    The status of each patient as regards LYM laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        LYM - SCR G0; SE G0
    18
        LYM - SCR G0; SE G1
    13
        LYM - SCR G0; SE G2
    6
        LYM - SCR G0; SE G3
    0
        LYM - SCR G0; SE G4
    0
        LYM - SCR G0; SE UNK
    2
        LYM - SCR G1; SE G0
    2
        LYM - SCR G1; SE G1
    4
        LYM - SCR G1; SE G2
    3
        LYM - SCR G1; SE G3
    0
        LYM - SCR G1; SE G4
    0
        LYM - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Neutrophils (NEU) values by maximum grade

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    End point title
    Number of patients with abnormal Neutrophils (NEU) values by maximum grade
    End point description
    The status of each patient as regards NEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        NEU - SCR G0; SE G0
    39
        NEU - SCR G0; SE G1
    4
        NEU - SCR G0; SE G2
    1
        NEU - SCR G0; SE G3
    2
        NEU - SCR G0; SE G4
    0
        NEU - SCR G0; SE UNK
    2
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Partial Thromboplastin Time (PTT) values by maximum grade

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    End point title
    Number of patients with abnormal Partial Thromboplastin Time (PTT) values by maximum grade
    End point description
    The status of each patient as regards PTT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        PTT - SCR G0; SE G0
    35
        PTT - SCR G0; SE G1
    3
        PTT - SCR G0; SE G2
    0
        PTT - SCR G0; SE G3
    1
        PTT - SCR G0; SE G4
    0
        PTT - SCR G0; SE UNK
    7
        PTT - SCR G1; SE G0
    0
        PTT - SCR G1; SE G1
    1
        PTT - SCR G1; SE G2
    0
        PTT - SCR G1; SE G3
    1
        PTT - SCR G1; SE G4
    0
        PTT - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with abnormal Platelets(PLT) values by maximum grade

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    End point title
    Number of patients with abnormal Platelets(PLT) values by maximum grade
    End point description
    The status of each patient as regards PLT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
    End point type
    Secondary
    End point timeframe
    From study start to study end, each patient being censored out of the analysis at time of death.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        PLT - SCR G0; SE G0
    39
        PLT - SCR G0; SE G1
    5
        PLT - SCR G0; SE G2
    1
        PLT - SCR G0; SE G3
    0
        PLT - SCR G0; SE G4
    0
        PLT - SCR G0; SE UNK
    2
        PLT - SCR G1; SE G0
    1
        PLT - SCR G1; SE G1
    0
        PLT - SCR G1; SE G2
    0
        PLT - SCR G1; SE G3
    0
        PLT - SCR G1; SE G4
    0
        PLT - SCR G1; SE UNK
    0
    No statistical analyses for this end point

    Secondary: Number of patients with any adverse events (AEs) and with AEs by maximum grade

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    End point title
    Number of patients with any adverse events (AEs) and with AEs by maximum grade
    End point description
    An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.
    End point type
    Secondary
    End point timeframe
    Within the 31-day follow-up period post treatment administration.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        Patients with any AEs
    48
        Patients with G1 AEs
    14
        Patients with G2 AEs
    19
        Patients with G3 AEs
    12
        Patients with G4 AEs
    3
        Patients with G5 AEs
    0
    No statistical analyses for this end point

    Secondary: Number of patients with any serious adverse events (SAEs) and with AEs by maximum grade

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    End point title
    Number of patients with any serious adverse events (SAEs) and with AEs by maximum grade
    End point description
    SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient, is a Grade 4 AE according to the CTCAE, version3.0. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.
    End point type
    Secondary
    End point timeframe
    Within the 31-day follow-up period post treatment administration.
    End point values
    MAGE-A3 Group
    Number of subjects analysed
    48
    Units: Subjects
        Patients with any SAEs
    10
        Patients with G1 SAEs
    1
        Patients with G2 SAEs
    2
        Patients with G3 SAEs
    5
        Patients with G4 SAEs
    2
        Patients with G5 SAEs
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs: From screening (SCR) up to study end; AEs: Within the 31-day follow-up period post treatment administration, up to study end.
    Adverse event reporting additional description
    The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    MAGE-A3 Group
    Reporting group description
    Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles

    Serious adverse events
    MAGE-A3 Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 48 (20.83%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    MAGE-A3 Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    48 / 48 (100.00%)
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    25 / 48 (52.08%)
         occurrences all number
    25
    Injection site pain
         subjects affected / exposed
    18 / 48 (37.50%)
         occurrences all number
    18
    Pyrexia
         subjects affected / exposed
    14 / 48 (29.17%)
         occurrences all number
    14
    Injection site reaction
         subjects affected / exposed
    9 / 48 (18.75%)
         occurrences all number
    9
    Influenza like illness
         subjects affected / exposed
    9 / 48 (18.75%)
         occurrences all number
    9
    Fatigue
         subjects affected / exposed
    9 / 48 (18.75%)
         occurrences all number
    9
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    22 / 48 (45.83%)
         occurrences all number
    22
    Constipation
         subjects affected / exposed
    14 / 48 (29.17%)
         occurrences all number
    14
    Vomiting
         subjects affected / exposed
    13 / 48 (27.08%)
         occurrences all number
    13
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    11 / 48 (22.92%)
         occurrences all number
    11

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jul 2008
    The changes following this Amendment concern: • The threshold value of LDH as inclusion criterion • The procedures to be performed at each visit for treatment administration
    02 Mar 2009
    The changes following this amendment concern: • The possibility of taking a new tumor biopsy in case the results of the analysis of the biopsies originally taken are inconclusive. • Clarification that MAGE-A3 testing and gene profiling of newly dissected tumors in case of disease progression require specific informed consent by the patients. • Clarification of the number of target lesions
    16 Oct 2009
    The changes following this amendment concern: • The number of patients to be enrolled has been increased from 20 to 40 in order to assess the gene profile data in patients who also receive chemotherapy. A pre-specified gene signature was identified in previous studies, but has not yet been assessed in patients receiving chemotherapy. Based on existing data, it is estimated that approximately 50% of patients will have a pre-specified gene signature. Therefore, the sample size should be doubled to have approximately 20 patients with and 20 patients without the pre-specified gene signature. Final analyses will be assessed in the overall population and in subsets with or without the pre-specified gene signature. As many patients currently enrolled in the study have agreed to allow gene profiling of their tumor sample it will remain an optional procedure. • The duration of follow-up for survival, disease progression and SAEs related to study participation and concurrent medication has been extended from 4 to 5 years after first treatment administration to obtain continued information regarding the patients’ health status after the treatment phase. • Overall survival has been added as a secondary endpoint.
    16 Jul 2010
    The changes following this amendment concern the avoidance of repeating procedures (biopsy and tumor imaging) during the screening phase, which may already have been performed recently prior to screening as part of local routine practice or in relation to another research study. It has also been made clear that any second-line therapy and not only second-line chemotherapy after the study treatment is of interest.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    18 Jul 2014
    Early end of trial notification after termination of long term follow up due to lack of scientific justification to continue collect information.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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