Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A multicentre randomised phase III trial comparing pembrolizumab versus standard chemotherapy for advanced pre-treated malignant pleural mesothelioma

    Summary
    EudraCT number
    		 2016-002062-31
    Trial protocol
    		 GB   ES  
    Global end of trial date
    21 Aug 2019

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ETOP9-15PROMISE-meso
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02991482
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Sharp & Dohme number: 3475-594
    Sponsors
    Sponsor organisation name
    European Thoracic Oncology Platform
    Sponsor organisation address
    Effingerstr. 40, Bern, Germany, 3008
    Public contact
    ETOP Coordinating Office, ETOP, +41 31 511 94 00, regulatoryoffice@etop-eu.org
    Scientific contact
    ETOP Coordinating Office, ETOP, +41 31 511 94 00, regulatoryoffice@etop-eu.org
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Aug 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Feb 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Aug 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate whether pre-treated mesothelioma patients treated with pembrolizumab have a better outcome in terms of progression-free survival (PFS), as assessed by independent radiological review, compared to standard, institutional-choice chemotherapy (gemcitabine or vinorelbine).
    Protection of trial subjects
    Pembrolizumab was withheld for all grade ≥3 (grade 2 for pneumonitis) drug-related toxicities including laboratory abnormalities, and severe or life-threatening adverse events (AEs). Pembrolizumab infusion reaction treatment guidelines were provided. Patients received appropriate supportive care measures as deemed necessary by the treating investigator (treatment delay and supportive care guidelines for pembrolizumab related AEs were also provided). Patients who experienced a recurrence of the same Serious Adverse Event at the same grade or greater with rechallenge of pembrolizumab, discontinued trial medication. At documented disease progression according to RECIST 1.1 criteria, patients in the control arm were allowed to receive pembrolizumab, if they met the cross-over criteria (ECOG PS 0 or 1, absence of progressive tumour at critical anatomical sites requiring urgent alternative medical intervention).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Apr 2017
    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
    Spain: 10
    Country: Number of subjects enrolled
    United Kingdom: 107
    Country: Number of subjects enrolled
    Switzerland: 27
    Worldwide total number of subjects
    144
    EEA total number of subjects
    117
    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)
    41
    From 65 to 84 years
    103
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 In total, 144 patients were randomised to either Pembrolizumab or to chemotherapy arms in a time duration of 12 months (first patient was randomised in September 2017; last patient was randomised in August 2018).

    Pre-assignment
    Screening details
    		 As of February 2019, 151 patients were captured in iBiobank. Of them, 7 were considered ineligible mainly due to life expectancy of <3 months or ECOG PS >1.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This is an open-label trial: the patient, the trial site personnel, the sponsor and/or designee are not blinded to treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pembrolizumab
    Arm description
    		 Pembrolizumab, 200 mg fixed dose i.v. on day 1 of every 3-week (±3 days) cycle until progression of disease determined according to RECIST 1.1 criteria or lack of tolerability or until further protocol treatment is declined by the patient, for a maximum of 2 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Pembrolizumab was administered at 200 mg fixed dose i.v. on day 1 of every 3-week (±3 days) cycle until progression of disease determined according to RECIST 1.1 criteria or lack of tolerability or until further protocol treatment is declined by the patient, for a maximum of 2 years. In case of clinical benefit, with physician and patient agreement, pembrolizumab treatment can continue beyond documented disease progression according to RECIST 1.1 criteria until a maximum of 2 years on pembrolizumab treatment is reached.

    Arm title
    		 Chemotherapy
    Arm description
    		 Vinorelbine (p.o.) or vinorelbine (i.v.) or gemcitabine on a per-patient basis prior to randomisation.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Vinorelbine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Vinorelbine i.v. 30 mg/m2 i.v., day 1 and day 8 of every 3-week (±3 days) cycle. A maximum number of treatment cycles was not mandated.

    Investigational medicinal product name
    Vinorelbine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Vinorelbine 60/80 mg/m2 p.o., day 1 and day 8 of every 3-week (±3 days) cycle. A maximum number of treatment cycles was not mandated.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Gemcitabine 1000 mg/m2 i.v., day 1 and day 8 of every 3-week (±3 days) cycle. A maximum number of treatment cycles was not mandated.

    Number of subjects in period 1
    		Pembrolizumab Chemotherapy
    Started
    73
    71
    Completed
    8
    5
    Not completed
    65
    66
         Patient decision
    1
    1
         Physician decision
    -
    6
         Disease progression
    56
    47
         Adverse event, non-fatal
    1
    6
         Death
    4
    4
         Patient feeling too unwell
    1
    -
         Clinical deterioration
    1
    -
         Death prior to study drug initiation
    1
    -
         Worsening of performance status
    -
    1
         Consent withdrawal prior to study drug initiation
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Pembrolizumab, 200 mg fixed dose i.v. on day 1 of every 3-week (±3 days) cycle until progression of disease determined according to RECIST 1.1 criteria or lack of tolerability or until further protocol treatment is declined by the patient, for a maximum of 2 years.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Vinorelbine (p.o.) or vinorelbine (i.v.) or gemcitabine on a per-patient basis prior to randomisation.

    Reporting group values
    		 Pembrolizumab Chemotherapy Total
    Number of subjects
    		 73 71 144
    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
        median (full range (min-max))
    		 69 (52 to 83) 71 (53 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 15 11 26
        Male
    		 58 60 118
    Region of enrolment
    Units: Subjects
        United Kingdom
    		 54 53 107
        Switzerland
    		 13 14 27
        Spain
    		 6 4 10
    Histologic subtype
    Units: Subjects
        Epithelioid
    		 66 62 128
        Non-epithelioid
    		 7 9 16
    Smoking history
    Units: Subjects
        Current
    		 5 4 9
        Former (≥100 cigarettes in the whole life)
    		 34 28 62
        Never (0-99 cigarettes in the whole life)
    		 33 39 72
        Unknown/Missing
    		 1 0 1
    ECOG Performance Status
    Of note, although an ECOG performance status (PS) of 0 or 1 was mandatory to be included in the study, one patient was allowed to enter the study with ECOG PS of 2 due to leg braces.
    Units: Subjects
        Zero
    		 21 14 35
        One
    		 51 57 108
        Two
    		 1 0 1
    EORTC score
    Units: Subjects
        Good prognosis
    		 45 54 99
        Poor prognosis
    		 28 17 45
    Prior treatment
    Units: Subjects
        Carboplatin/Pemetrexed
    		 27 27 54
        Cisplatin/Pemetrexed
    		 24 22 46
        Platinum+/-Pemetrexed+/-Other
    		 13 17 30
        Cisplatin/Pemetrexed and Carboplatin/Pemetrexed
    		 7 1 8
        Missing
    		 2 4 6
    PD-L1 score
    Units: Subjects
        <1%
    		 36 30 66
        1-20%
    		 20 18 38
        ≥20%
    		 11 14 25
        Not evaluable
    		 2 4 6
        Not scored
    		 4 5 9

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Pembrolizumab
    Reporting group description
    		 Pembrolizumab, 200 mg fixed dose i.v. on day 1 of every 3-week (±3 days) cycle until progression of disease determined according to RECIST 1.1 criteria or lack of tolerability or until further protocol treatment is declined by the patient, for a maximum of 2 years.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Vinorelbine (p.o.) or vinorelbine (i.v.) or gemcitabine on a per-patient basis prior to randomisation.

    Primary: Progression Free Survival (PFS) as assessed by independent radiological review

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) as assessed by independent radiological review
    End point description
    PFS is defined as the time from the date of randomization until documented progression by independent radiological review or death, if progression was not documented. If no PFS event was recorded, last tumor assessment date was considered as the censoring date.
    End point type
    Primary
    End point timeframe
    Time from randomization of the first patient until database cutoff date for the primary PFS analysis (Sep 2017 - Feb 2019; approximately 1.5 years).
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    73
    71
    Units: months
        median (confidence interval 95%)
    2.5 (2.1 to 4.2)
    3.4 (2.2 to 4.3)
    Statistical analysis title
    		 Statistical analysis of the primary endpoint
    Comparison groups
    Pembrolizumab v Chemotherapy
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.53
    Notes
    [1] - Logrank stratified by histologic subtype

    Secondary: Objective response rate by independent radiological review

    		 Close Top of page
    End point title
    		 Objective response rate by independent radiological review
    End point description
    Defined as the best overall response (complete or partial) by independent radiological review, across all assessment time-points from randomization to the end of trial treatment, determined by RECIST 1.1 criteria.
    End point type
    Secondary
    End point timeframe
    Time from randomization of the first patient until termination of trial treatment.
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    73
    71
    Units: percentage
        number (confidence interval 95%)
    21.9 (13.1 to 33.1)
    5.6 (1.6 to 13.8)
    No statistical analyses for this end point

    Secondary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    Defined as time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date.
    End point type
    Secondary
    End point timeframe
    Time from randomization of the first patient until database cutoff date for the OS analysis (Sep 2017 - Aug 2019; approximately 2 years).
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    73
    71
    Units: months
        median (confidence interval 95%)
    10.7 (7.6 to 15.0)
    12.4 (7.4 to 16.1)
    No statistical analyses for this end point

    Secondary: Time to treatment failure

    		 Close Top of page
    End point title
    		 Time to treatment failure
    End point description
    Time from from randomisation to discontinuation of treatment for any reason, including progression of disease, treatment toxicity, refusal or death. Censoring will occur at the last follow-up date.
    End point type
    Secondary
    End point timeframe
    Time from randomization of the first patient until database cutoff date for the primary PFS analysis (Sep 2017 - Feb 2019; approximately 1.5 years).
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    73
    71
    Units: months
        median (confidence interval 95%)
    2.8 (2.1 to 4.2)
    2.3 (2.1 to 3.9)
    No statistical analyses for this end point

    Secondary: Safety and tolerability

    		 Close Top of page
    End point title
    		 Safety and tolerability
    End point description
    The safety and tolerability of pembrolizumab treatment will be assessed through analysis of the worst grade of toxicity/adverse events according to CTCAE v4.0 criteria observed over the whole treatment period.
    End point type
    Secondary
    End point timeframe
    Adverse events are collected from study treatment initiation to 30 days after treatment is ceased for any reason. Serious adverse events and events of clinical interest are collected within 90 days after last dose of trial treatment.
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    72
    70
    Units: Subjects
        Any AE
    70
    65
        Treatment related AE
    50
    52
        Treatment related AE of grade 3-5
    14
    18
        Treatment related AE leading to death
    1
    1
        Treatment realted AE leading to treatment stop
    5
    5
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) assessed by investigator

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) assessed by investigator
    End point description
    Investigator assessed PFS, from the date of randomisation until documented progression or death, if progression is not documented. Censoring occurs at the last tumor assessment.
    End point type
    Secondary
    End point timeframe
    Time from randomization of the first patient until database cutoff date for the primary PFS analysis (Sep 2017 - Feb 2019; approximately 1.5 years).
    End point values
    		 Pembrolizumab Chemotherapy
    Number of subjects analysed
    73
    71
    Units: Months
        median (confidence interval 95%)
    3.5 (2.1 to 4.2)
    3.7 (2.2 to 4.3)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were collected from study treatment initiation until 30 days after all trial treatment discontinuation. Serious adverse events and events of clinical interest were collected within 90 days after last treatment dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Pembrolizumab arm (safety cohort)
    Reporting group description
    		 Safety cohort consists of patients that have received at least one dose of trial treatment.

    Reporting group title
    Chemotherapy (safety cohort)
    Reporting group description
    		 Safety cohort consists of patients that have received at least one dose of trial treatment.

    Serious adverse events
    		 Pembrolizumab arm (safety cohort) Chemotherapy (safety cohort)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    27 / 72 (37.50%)
    22 / 70 (31.43%)
         number of deaths (all causes)
    47
    16
         number of deaths resulting from adverse events
    Vascular disorders
    Thromboembolic event
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophysitis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    4 / 72 (5.56%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alkaline phosphatase increased
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart failure
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 70 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhea
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Lung infection
         subjects affected / exposed
    4 / 72 (5.56%)
    8 / 70 (11.43%)
         occurrences causally related to treatment / all
    1 / 4
    4 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchial infection
         subjects affected / exposed
    2 / 72 (2.78%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter related infection
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection NOS
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-neutropaenic infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcemia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalemia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pembrolizumab arm (safety cohort) Chemotherapy (safety cohort)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    70 / 72 (97.22%)
    65 / 70 (92.86%)
    Investigations
    GGT increased
         subjects affected / exposed
    5 / 72 (6.94%)
    1 / 70 (1.43%)
         occurrences all number
    5
    1
    Weight loss
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 70 (4.29%)
         occurrences all number
    5
    3
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 72 (5.56%)
    4 / 70 (5.71%)
         occurrences all number
    4
    4
    Neutrophil count decreased
         subjects affected / exposed
    0 / 72 (0.00%)
    10 / 70 (14.29%)
         occurrences all number
    0
    10
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 72 (5.56%)
    6 / 70 (8.57%)
         occurrences all number
    4
    6
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 70 (5.71%)
         occurrences all number
    1
    4
    Paresthesia
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 70 (5.71%)
         occurrences all number
    1
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    28 / 72 (38.89%)
    32 / 70 (45.71%)
         occurrences all number
    28
    32
    Pain
         subjects affected / exposed
    19 / 72 (26.39%)
    19 / 70 (27.14%)
         occurrences all number
    19
    19
    Edema limbs
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 70 (5.71%)
         occurrences all number
    6
    4
    Flu like symptoms
         subjects affected / exposed
    5 / 72 (6.94%)
    2 / 70 (2.86%)
         occurrences all number
    5
    2
    Fever
         subjects affected / exposed
    2 / 72 (2.78%)
    5 / 70 (7.14%)
         occurrences all number
    2
    5
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    3 / 72 (4.17%)
    11 / 70 (15.71%)
         occurrences all number
    3
    11
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    17 / 72 (23.61%)
    23 / 70 (32.86%)
         occurrences all number
    17
    23
    Nausea
         subjects affected / exposed
    16 / 72 (22.22%)
    24 / 70 (34.29%)
         occurrences all number
    16
    24
    Diarrhea
         subjects affected / exposed
    16 / 72 (22.22%)
    26 / 70 (37.14%)
         occurrences all number
    16
    26
    Vomiting
         subjects affected / exposed
    10 / 72 (13.89%)
    8 / 70 (11.43%)
         occurrences all number
    10
    8
    Mucositis oral
         subjects affected / exposed
    5 / 72 (6.94%)
    9 / 70 (12.86%)
         occurrences all number
    5
    9
    Dry mouth
         subjects affected / exposed
    3 / 72 (4.17%)
    4 / 70 (5.71%)
         occurrences all number
    3
    4
    Abdominal pain
         subjects affected / exposed
    2 / 72 (2.78%)
    8 / 70 (11.43%)
         occurrences all number
    2
    8
    Oral thrush
         subjects affected / exposed
    4 / 72 (5.56%)
    2 / 70 (2.86%)
         occurrences all number
    4
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnea
         subjects affected / exposed
    20 / 72 (27.78%)
    10 / 70 (14.29%)
         occurrences all number
    20
    10
    Cough
         subjects affected / exposed
    16 / 72 (22.22%)
    3 / 70 (4.29%)
         occurrences all number
    16
    3
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    11 / 72 (15.28%)
    2 / 70 (2.86%)
         occurrences all number
    11
    2
    Dry skin
         subjects affected / exposed
    11 / 72 (15.28%)
    3 / 70 (4.29%)
         occurrences all number
    11
    3
    Pruritus
         subjects affected / exposed
    10 / 72 (13.89%)
    3 / 70 (4.29%)
         occurrences all number
    10
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    8 / 72 (11.11%)
    5 / 70 (7.14%)
         occurrences all number
    8
    5
    Depression
         subjects affected / exposed
    3 / 72 (4.17%)
    4 / 70 (5.71%)
         occurrences all number
    3
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 72 (9.72%)
    2 / 70 (2.86%)
         occurrences all number
    7
    2
    Back pain
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 70 (4.29%)
         occurrences all number
    5
    3
    Myalgia
         subjects affected / exposed
    5 / 72 (6.94%)
    0 / 70 (0.00%)
         occurrences all number
    5
    0
    Chest wall pain
         subjects affected / exposed
    0 / 72 (0.00%)
    4 / 70 (5.71%)
         occurrences all number
    0
    4
    Infections and infestations
    Lung infection
         subjects affected / exposed
    6 / 72 (8.33%)
    2 / 70 (2.86%)
         occurrences all number
    6
    2
    Urinary tract infection
         subjects affected / exposed
    5 / 72 (6.94%)
    2 / 70 (2.86%)
         occurrences all number
    5
    2
    Bronchial infection
         subjects affected / exposed
    4 / 72 (5.56%)
    2 / 70 (2.86%)
         occurrences all number
    4
    2
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    12 / 72 (16.67%)
    21 / 70 (30.00%)
         occurrences all number
    12
    21
    Hypoalbuminemia
         subjects affected / exposed
    4 / 72 (5.56%)
    2 / 70 (2.86%)
         occurrences all number
    4
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 06:44:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA