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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    Combination therapy with Nivolumab and PD-L1/IDO peptide vaccine with Montanide to patients with metastatic malignant melanoma

    Summary
    EudraCT number
    		 2016-004527-23
    Trial protocol
    		 DK  
    Global end of trial date
    31 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jan 2023
    First version publication date
    19 Jan 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MM1636
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03047928
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    National Center for Cancer Immune Therapy
    Sponsor organisation address
    Borgmester Ib Juuls Vej 25C, 5th floor, Herlev Hospital, Denmark, 2730
    Public contact
    Trial Executive, National Center for Cancer Immune Therapy (CCIT-DK), inge.marie.svane@regionh.dk
    Scientific contact
    Trial Executive, National Center for Cancer Immune Therapy (CCIT-DK), cathrine.lund.lorentzen@regionh.dk
    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
    31 Dec 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Dec 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Dec 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To asses safety and tolerability of combination therapy with Nivolumab and the PD-L1/IDO peptide vaccine with the adjuvant Montanide in patients with metastatic malignant melanoma
    Protection of trial subjects
    Trial subjects were evaluated by the PI or another doctor from the CCIT-DK at every appointment regarding the clinical trial. During the trial period, the patients could call the PI directly if they had any concerns or questions.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 30
    Worldwide total number of subjects
    30
    EEA total number of subjects
    30
    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)
    7
    From 65 to 84 years
    22
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 All patients were recruited from Danish oncology centers between 2017-2022.

    Pre-assignment
    Screening details
    		 Patients eligible for therapy were screening at Herlev Hospital according to in- and exclusion criteria described in the protocol.

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

    Arms
    Arm title
    		 Arm A
    Arm description
    		 Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 14 days for 24 cycles. Patients with ongoing responses could continue nivolumab (6 mg/kg, monthly) for two years or until progressive disease.

    Investigational medicinal product name
    IDO/PD-L1 vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    IDO/PD-L1 vaccine consisted of: 100 μg of 21-amino-acid peptide sequences from IDO (DTLLKALLEIASCLEKALQVF) and 100 μg of 19-amino-acid peptide sequences from PD-L1 (FMTYWHLLNAFTVTVPKDL)

    Number of subjects in period 1
    		Arm A
    Started
    30
    Completed
    30
    Period 2
    Period 2 title
    period 2
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm B
    Arm description
    		 Extension cohort. Progressive disease ON anti-PD-1 monotherapy.Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 14 days for 24 cycles. Patients with ongoing responses could continue nivolumab (6 mg/kg, monthly) for two years or until progressive disease.

    Investigational medicinal product name
    IDO/PD-L1 vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    IDO/PD-L1 vaccine consisted of: 100 μg of 21-amino-acid peptide sequences from IDO (DTLLKALLEIASCLEKALQVF) and 100 μg of 19-amino-acid peptide sequences from PD-L1 (FMTYWHLLNAFTVTVPKDL)

    Arm title
    		 Arm C
    Arm description
    		 Extension cohort. Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy. Subjects should not have discontinued antibody therapy due to serious and/or lifethreatening toxicity. At the end of trial, four of ten expected patients were included and treated in Arm C.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3 mg/kg every 14 days for 24 cycles. Patients with ongoing responses could continue nivolumab (6 mg/kg, monthly) for two years or until progressive disease.

    Investigational medicinal product name
    IDO/PD-L1 vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    IDO/PD-L1 vaccine consisted of: 100 μg of 21-amino-acid peptide sequences from IDO (DTLLKALLEIASCLEKALQVF) and 100 μg of 19-amino-acid peptide sequences from PD-L1 (FMTYWHLLNAFTVTVPKDL)

    Number of subjects in period 2 [1]
    		Arm B Arm C
    Started
    14
    4
    Completed
    10
    4
    Not completed
    4
    0
         Adverse event, non-fatal
    2
    -
         included in another trial
    1
    -
         Protocol deviation
    1
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number of subjects in the original cohort (Cohort A) was 30. Two cohorts (B and C) with ten patients in each cohort were amended

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.

    Reporting group values
    		 Arm A Total
    Number of subjects
    		 30 30
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 7 7
        From 65-84 years
    		 22 22
        85 years and over
    		 1 1
    Gender categorical
    Units: Subjects
        Female
    		 14 14
        Male
    		 16 16

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.
    Reporting group title
    Arm B
    Reporting group description
    		 Extension cohort. Progressive disease ON anti-PD-1 monotherapy.Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.

    Reporting group title
    Arm C
    Reporting group description
    		 Extension cohort. Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy. Subjects should not have discontinued antibody therapy due to serious and/or lifethreatening toxicity. At the end of trial, four of ten expected patients were included and treated in Arm C.

    Primary: Adverse events

    		 Close Top of page
    End point title
    		 Adverse events [1]
    End point description
    The primary endpoint is adverse events (AE) assessed by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. The SAEs are listed under "Advderse Events"
    End point type
    Primary
    End point timeframe
    December 2017 - December 2022
    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: There were no statistical analyses specified for this primary end point
    End point values
    		 Arm A
    Number of subjects analysed
    30
    Units: CTCAE 4.0 (0-5)
    30
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    December 2017 - December 2022
    Adverse event reporting additional description
    The primary endpoint is adverse events (AE) assessed by Common Terminology Criteria for Adverse Events (CTCAE) 4.0
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.

    Reporting group title
    Arm B
    Reporting group description
    		 Extension cohort. Progressive disease ON anti-PD-1 monotherapy.Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.

    Reporting group title
    Arm C
    Reporting group description
    		 Extension cohort. Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy. Subjects should not have discontinued antibody therapy due to serious and/or lifethreatening toxicity. At the end of trial, four of ten expected patients were included and treated in Arm C.

    Serious adverse events
    		 Arm A Arm B Arm C
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 30 (36.67%)
    2 / 14 (14.29%)
    1 / 4 (25.00%)
         number of deaths (all causes)
    12
    6
    2
         number of deaths resulting from adverse events
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tonsillar disorder
    Additional description: Tonsillectomy due to PET positive focus in tonsil. The process was bening.
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocarditis
    Additional description: suspected tretament realted myocarditis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebellar embolism
    Additional description: due to arterosclerosis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
    Additional description: treatment related
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gallbladder disorder
    Additional description: ESWL treatment (had received several ESWL treatments prior to trial therapy)
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
    Additional description: Suspected melaena. No ulcer was found on gastroscopy. Resolved within a few days.
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
    Additional description: treatment related
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    pneumonitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
    Additional description: The patient was know with adrenal insufficiency. Admitted with influenza which led to uncontrolled adrenal insufficiency.
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophysitis
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Hip fracture
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Staphylococcal infection
    Additional description: Bacteremia.
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
    Additional description: e. coli bacterimia (probably caused by a urinary tract infection)
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Arm A Arm B Arm C
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 30 (100.00%)
    10 / 14 (71.43%)
    4 / 4 (100.00%)
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    17 / 30 (56.67%)
    3 / 14 (21.43%)
    3 / 4 (75.00%)
         occurrences all number
    17
    3
    3
    Infusion related reaction
    Additional description: related to nivolumab
         subjects affected / exposed
    5 / 30 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    5
    0
    0
    Granuloma skin
    Additional description: at injection site
         subjects affected / exposed
    20 / 30 (66.67%)
    5 / 14 (35.71%)
    1 / 4 (25.00%)
         occurrences all number
    20
    5
    1
    Injection related reaction
         subjects affected / exposed
    23 / 30 (76.67%)
    4 / 14 (28.57%)
    2 / 4 (50.00%)
         occurrences all number
    23
    4
    2
    Injection site erythema
    Additional description: redness at injection site
         subjects affected / exposed
    7 / 30 (23.33%)
    1 / 14 (7.14%)
    2 / 4 (50.00%)
         occurrences all number
    7
    1
    2
    Injection site pruritus
    Additional description: pruritus
         subjects affected / exposed
    4 / 30 (13.33%)
    3 / 14 (21.43%)
    1 / 4 (25.00%)
         occurrences all number
    4
    3
    1
    Injection site pain
    Additional description: pain
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    4
    0
    1
    Injection site discomfort
    Additional description: myalgia
         subjects affected / exposed
    5 / 30 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    5
    0
    0
    Ear and labyrinth disorders
    Hearing disability
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Dry eye
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Dry mouth
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    5
    1
    0
    Nausea
         subjects affected / exposed
    8 / 30 (26.67%)
    3 / 14 (21.43%)
    1 / 4 (25.00%)
         occurrences all number
    8
    3
    1
    Stomatitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    4
    4
    4
    Abdominal pain
         subjects affected / exposed
    4 / 30 (13.33%)
    2 / 14 (14.29%)
    1 / 4 (25.00%)
         occurrences all number
    4
    2
    1
    colitis
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    Constipation
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
         occurrences all number
    2
    1
    1
    Diarrhoea
         subjects affected / exposed
    9 / 30 (30.00%)
    2 / 14 (14.29%)
    1 / 4 (25.00%)
         occurrences all number
    9
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    7 / 30 (23.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    7
    1
    0
    Pleural effusion
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Pneumonitis
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    8 / 30 (26.67%)
    2 / 14 (14.29%)
    0 / 4 (0.00%)
         occurrences all number
    8
    5
    0
    Vitiligo
         subjects affected / exposed
    4 / 30 (13.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    4
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    16 / 30 (53.33%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
         occurrences all number
    16
    1
    1
    Dry skin
         subjects affected / exposed
    8 / 30 (26.67%)
    3 / 14 (21.43%)
    1 / 4 (25.00%)
         occurrences all number
    8
    3
    1
    Endocrine disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Amylase increased
         subjects affected / exposed
    6 / 30 (20.00%)
    2 / 14 (14.29%)
    0 / 4 (0.00%)
         occurrences all number
    6
    2
    0
    Hypophysitis
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    Adrenal insufficiency
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    5 / 30 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    5
    0
    0
    Arthralgia
         subjects affected / exposed
    11 / 30 (36.67%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    11
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Sep 2018
    Two new patient cohorts were added to the trial: Cohort B: Extension cohort (10 patients). Progressive disease ON anti-PD-1 monotherapy.Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy. Cohort C: Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy. Subjects should not have discontinued antibody therapy due to serious and/or lifethreatening toxicity

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/34887574
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 00:18:02 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA