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    Clinical Trial Results:
    A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination with Novel Agents in Subjects with Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)

    Summary
    EudraCT number
    		 2018-002932-26
    Trial protocol
    		 FR   PT   ES   IT  
    Global end of trial date
    13 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jan 2022
    First version publication date
    28 Jan 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D9108C00002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03794544
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca Clinical Study Information Center
    Sponsor organisation address
    OneMedImmune Way, Gaithersburg, United States, MD 20878
    Public contact
    Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 18772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 18772409479, information.center@astrazeneca.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
    15 Sep 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Jan 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the antitumor activity of durvalumab alone and/or in combination with novel agents.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Mar 2019
    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
    Canada: 2
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United States: 65
    Worldwide total number of subjects
    84
    EEA total number of subjects
    16
    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)
    32
    From 65 to 84 years
    50
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 84 participants were enrolled across 7 countries worldwide.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Durvalumab 1500 mg
    Arm description
    		 Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg was administered IV Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Arm title
    		 Durvalumab 1500 mg + Oleclumab 3000 mg
    Arm description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    MEDI9447
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Oleclumab 3000 mg was administered IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg was administered IV Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Arm title
    		 Durvalumab 1500 mg + Monalizumab 750 mg
    Arm description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg was administered IV Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Investigational medicinal product name
    Monalizumab
    Investigational medicinal product code
    IPH2201
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Monalizumab 750 mg was administered IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Arm title
    		 Durvalumab 1500 mg + Danvatirsen 200 mg
    Arm description
    		 Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Danvatirsen
    Investigational medicinal product code
    AZD9150
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Danvatirsen 200 mg was administered IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1500 mg was administered IV Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.

    Number of subjects in period 1
    		Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Started
    27
    21
    20
    16
    Treated
    26
    21
    20
    16
    Completed
    26
    18
    19
    15
    Not completed
    1
    3
    1
    1
         Adverse event, serious fatal
    -
    -
    -
    1
         Consent withdrawn by subject
    1
    1
    -
    -
         Unspecified
    -
    1
    -
    -
         Lost to follow-up
    -
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Durvalumab 1500 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Oleclumab 3000 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Monalizumab 750 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Danvatirsen 200 mg
    Reporting group description
    		 Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg Total
    Number of subjects
    		 27 21 20 16 84
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 11 10 10 1 32
        From 65-84 years
    		 16 11 10 13 50
        85 years and over
    		 0 0 0 2 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 67.1 ( 9.0 ) 65.5 ( 7.5 ) 65.1 ( 6.3 ) 72.9 ( 7.9 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 13 9 6 6 34
        Male
    		 14 12 14 10 50
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 1 0 0 1 2
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 3 1 1 0 5
        White
    		 23 20 19 13 75
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 2 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 0 0 2 3
        Not Hispanic or Latino
    		 26 21 20 14 81
        Unknown or Not Reported
    		 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Durvalumab 1500 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Oleclumab 3000 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Monalizumab 750 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Danvatirsen 200 mg
    Reporting group description
    		 Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Primary: Major Pathological Response Rate

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    End point title
    		 Major Pathological Response Rate [1]
    End point description
    Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen. Intent-to-treat (ITT) population was analysed which included participants who were randomized and were analyzed according to their randomized treatment group.
    End point type
    Primary
    End point timeframe
    Day 1 through Day 42
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    27
    21
    20
    16
    Units: Percentage of participants
        number (confidence interval 95%)
    11.1 (2.4 to 29.2)
    19.0 (5.4 to 41.9)
    30.0 (11.9 to 54.3)
    31.3 (11.0 to 58.7)
    No statistical analyses for this end point

    Secondary: Pathological Complete Response (pCR) Rate

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    End point title
    		 Pathological Complete Response (pCR) Rate
    End point description
    The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen. The ITT population was analysed which included participants who were randomized and were analyzed according to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 42
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    27
    21
    20
    16
    Units: Percentage of participants
        number (confidence interval 95%)
    3.7 (0.1 to 19.0)
    9.5 (1.2 to 30.4)
    10.0 (1.2 to 31.7)
    12.5 (1.6 to 38.3)
    No statistical analyses for this end point

    Secondary: Feasibility to Surgery

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    End point title
    		 Feasibility to Surgery
    End point description
    Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1. As-treated population was analysed which included all participants who received any study drug and analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 29 to Day 42 after Week 1 Day 1
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    26
    21
    20
    16
    Units: Percentage of participants
        number (not applicable)
    84.6
    81.0
    90.0
    93.8
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed which included all participants who received any study drug and analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    From Day 1 through Day 105
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    26
    21
    20
    16
    Units: Participants
        Any TEAEs
    18
    19
    15
    13
        Any TESAEs
    3
    2
    1
    5
    No statistical analyses for this end point

    Secondary: Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities

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    End point title
    		 Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
    End point description
    Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis. As-treated population was analysed which included all participants who received any study drug and analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    From Day 1 through Day 105
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    26
    21
    20
    16
    Units: Participants
        Alanine aminotransferase increased
    0
    0
    0
    2
        Gamma glutamyl transferase increased
    0
    0
    0
    1
        Lipase increased
    1
    1
    1
    0
        Hyponatremia
    2
    0
    0
    0
        Lymphocyte count decreased
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as TEAEs

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs
    End point description
    Participants with abnormal vital sign reported as TEAEs are reported. As-treated population was analysed which included all participants who received any study drug and analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    From Day 1 through Day 105
    End point values
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Number of subjects analysed
    26
    21
    20
    16
    Units: Participants
        Palpitations
    1
    0
    0
    0
        Pyrexia
    1
    2
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 through Day 105
    Adverse event reporting additional description
    As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Durvalumab 1500 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Oleclumab 3000 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Monalizumab 750 mg
    Reporting group description
    		 Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Reporting group title
    Durvalumab 1500 mg + Danvatirsen 200 mg
    Reporting group description
    		 Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).

    Serious adverse events
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    5 / 16 (31.25%)
         number of deaths (all causes)
    0
    0
    0
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Bronchial anastomosis complication
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Procedural haemorrhage
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericarditis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemothorax
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary air leakage
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal infarct
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Immune-mediated arthritis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Durvalumab 1500 mg Durvalumab 1500 mg + Oleclumab 3000 mg Durvalumab 1500 mg + Monalizumab 750 mg Durvalumab 1500 mg + Danvatirsen 200 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 26 (69.23%)
    19 / 21 (90.48%)
    14 / 20 (70.00%)
    13 / 16 (81.25%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Fatigue
         subjects affected / exposed
    6 / 26 (23.08%)
    4 / 21 (19.05%)
    2 / 20 (10.00%)
    3 / 16 (18.75%)
         occurrences all number
    6
    4
    2
    3
    Facial pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Generalised oedema
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    2 / 16 (12.50%)
         occurrences all number
    1
    3
    1
    2
    Epistaxis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    3 / 16 (18.75%)
         occurrences all number
    3
    1
    0
    3
    Haemoptysis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Nasal obstruction
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    0
    1
    Productive cough
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Depression
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Emotional distress
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    1
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    International normalised ratio decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    1
    1
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Tri-iodothyronine increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Prothrombin time shortened
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    1
    1
    Weight decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Injury, poisoning and procedural complications
    Post procedural discomfort
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    5 / 26 (19.23%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    2 / 16 (12.50%)
         occurrences all number
    0
    0
    1
    2
    Sciatica
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Syncope
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vocal cord paresis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nephrogenic anaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Visual impairment
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    0
    0
    0
    2
    Haemorrhoids
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Nausea
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    2
    3
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toothache
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    1
    1
    Erythema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Onychoclasis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 21 (9.52%)
    2 / 20 (10.00%)
    2 / 16 (12.50%)
         occurrences all number
    0
    2
    2
    2
    Rash maculo-papular
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    1
    1
    Rash
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Scar pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash pruritic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin discolouration
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    1
    1
    Arthralgia
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Bone pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Chest wall mass
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Muscle tightness
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Muscular weakness
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    Chest wall abscess
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Covid-19
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Nov 2018
    Doses should be omitted, and therapy may be discontinued at the discretion of the investigator, for toxicities that occurred in participants treated with durvalumab + oleclumab (>= Grade 2 pulmonary oedema or >= Grade 3 peripheral oedema). Electrocardiogram (ECG) assessments were added pre dose and immediately after the end of danvatirsen infusion on Week 0 Day 1 and Week 3 Day 1, respectively, and as clinically indicated. Pharmacokinetic assessments were added on Week 3, Day 1 to align with ECG assessments. The SRC would assess feasibility to surgery for all treatment arms and added safety measures in the event that one participant per treatment arm experienced a delay in receiving planned surgery.
    18 Jan 2019
    Participant population was revised to include participants with N2 disease (one single nodal station <= 3 cm only). Forced expiratory volume in one second and Diffusing capacity of the lungs for carbon monoxide requirements were revised from >= 60% to >= 50%. Participants who had a curative treated malignancy with no known active disease for > 2 years before enrolment on the study were eligible to enroll into this study. Monalizumab dose preparation, administration, and manufacturing process was updated.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    13 Apr 2020
    The trial was interrupted due to COVID-19 pandemic.
    07 May 2020

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The pharmacokinetic and immunogenicity samples are still being analyzed. Results for these outcome measures will be posted by 30Jun2022.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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