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    Clinical Trial Results:
    A randomized, open-label, phase II study of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant therapy in subjects with resectable non-small cell lung cancer (CANOPY-N)

    Summary
    EudraCT number
    		 2018-004813-42
    Trial protocol
    		 ES   FR   HU   NL   GR   DE   BE  
    Global end of trial date
    15 Aug 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jun 2023
    First version publication date
    28 Jun 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CACZ885V2201C
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03968419
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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 Aug 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Aug 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective/endpoint was to assess the MPR rate (≤10% of residual viable tumor cells) on the resected specimen per central review at the time of surgery in all subjects randomized to canakinumab alone and in combination with pembrolizumab treatment arms.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Nov 2019
    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
    Belgium: 2
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Japan: 4
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Russian Federation: 11
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    Taiwan: 5
    Country: Number of subjects enrolled
    Turkey: 9
    Country: Number of subjects enrolled
    United States: 16
    Worldwide total number of subjects
    88
    EEA total number of subjects
    40
    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)
    31
    From 65 to 84 years
    57
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted in 29 centers across 12 countries.

    Pre-assignment
    Screening details
    		 Screening assessments were done within 28 days prior to randomization. A total of 163 participants were screened. Of them, 88 participants were randomized. After treatment completion or discontinuation, all subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Canakinumab monotherapy
    Arm description
    		 Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks

    Arm title
    		 Canakinumab + pembrolizumab
    Arm description
    		 Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion, Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks

    Arm title
    		 Pembrolizumab monotherapy
    Arm description
    		 Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion, Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks

    Number of subjects in period 1
    		Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Started
    35
    35
    18
    Completed
    35
    35
    17
    Not completed
    0
    0
    1
         Adverse event, non-fatal
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Canakinumab monotherapy
    Reporting group description
    		 Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Canakinumab + pembrolizumab
    Reporting group description
    		 Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Pembrolizumab monotherapy
    Reporting group description
    		 Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy Total
    Number of subjects
    		 35 35 18 88
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 15 11 5 31
        From 65-84 years
    		 20 24 13 57
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 65.5 ( 9.88 ) 67.1 ( 6.98 ) 66.1 ( 5.61 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 13 14 9 36
        Male
    		 22 21 9 52
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 20 25 12 57
        Asian
    		 7 3 2 12
        Black or African American
    		 1 1 0 2
        American Indian or Alaska Native
    		 0 1 0 1
        Unknown
    		 7 5 4 16

    End points

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    End points reporting groups
    Reporting group title
    Canakinumab monotherapy
    Reporting group description
    		 Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Canakinumab + pembrolizumab
    Reporting group description
    		 Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Pembrolizumab monotherapy
    Reporting group description
    		 Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Primary: Major Pathological Response (MPR) rate at the time of surgery in subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review

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    End point title
    		 Major Pathological Response (MPR) rate at the time of surgery in subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review [1] [2]
    End point description
    MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.
    End point type
    Primary
    End point timeframe
    At time of surgery (up to 6 weeks after first dose of study treatment)
    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: No statistical analyses were planned for this primary end point
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive canakinumab monotherapy or canakinumab in combination with pembrolizumab.
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab
    Number of subjects analysed
    35
    35
    Units: Percentage of participants
        number (confidence interval 95%)
    2.9 (0.07 to 14.92)
    17.1 (6.56 to 33.65)
    No statistical analyses for this end point

    Secondary: Canakinumab ADA incidence

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    End point title
    		 Canakinumab ADA incidence [3]
    End point description
    Canakinumab ADA incidence on treatment was calculated as the percentage of participants who were canakinumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and canakinumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
    End point type
    Secondary
    End point timeframe
    From baseline (Predose on Day 1 of Cycle 1) up to 130 days after last dose of study treatment (assessed up to 24.6 weeks). Cycle = 21 days
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive canakinumab (as monotherapy or in combination with pembrolizumab).
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab
    Number of subjects analysed
    35
    35
    Units: Participants
    1
    0
    No statistical analyses for this end point

    Secondary: Canakinumab antidrug antibodies (ADA) prevalence

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    End point title
    		 Canakinumab antidrug antibodies (ADA) prevalence [4]
    End point description
    Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline
    End point type
    Secondary
    End point timeframe
    Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive canakinumab (as monotherapy or in combination with pembrolizumab).
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab
    Number of subjects analysed
    35
    35
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Secondary: Pembrolizumab ADA prevalence

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    End point title
    		 Pembrolizumab ADA prevalence [5]
    End point description
    Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline
    End point type
    Secondary
    End point timeframe
    Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive pembrolizumab (as monotherapy or in combination with canakinumab).
    End point values
    		 Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    18
    Units: Participants
    4
    3
    No statistical analyses for this end point

    Secondary: Pembrolizumab ADA incidence

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    End point title
    		 Pembrolizumab ADA incidence [6]
    End point description
    Pembrolizumab ADA incidence on treatment was calculated as the percentage of participants who were pembrolizumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and pembrolizumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
    End point type
    Secondary
    End point timeframe
    From baseline (Predose on Day 1 of Cycle 1) up to 26 days after last dose of study treatment (assessed up to 10.7 weeks). Cycle = 21 days
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive pembrolizumab (as monotherapy or in combination with canakinumab).
    End point values
    		 Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    18
    Units: Participants
    3
    4
    No statistical analyses for this end point

    Secondary: Overall response rate (ORR) based on local investigator assessment using RECIST v1.1

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    End point title
    		 Overall response rate (ORR) based on local investigator assessment using RECIST v1.1
    End point description
    ORR is defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per local investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
    End point type
    Secondary
    End point timeframe
    From date of randomization to date of surgery, assessed up to 6 weeks
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    35
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.00 to 10.00)
    8.6 (1.80 to 23.06)
    11.1 (1.38 to 34.71)
    No statistical analyses for this end point

    Secondary: Serum canakinumab concentration

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    End point title
    		 Serum canakinumab concentration [7]
    End point description
    Canakinumab serum concentrations were determined at the specified time points.
    End point type
    Secondary
    End point timeframe
    Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive canakinumab (as monotherapy or in combination with pembrolizumab).
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab
    Number of subjects analysed
    35
    35
    Units: microgram/miliLiter (ug/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1
    0 ( 0 )
    0 ( 0 )
        Cycle 2
    10.9 ( 32.9 )
    10.3 ( 41.0 )
    No statistical analyses for this end point

    Secondary: Serum pembrolizumab concentration

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    End point title
    		 Serum pembrolizumab concentration [8]
    End point description
    Pembrolizumab serum concentrations were determined at the specified time points.
    End point type
    Secondary
    End point timeframe
    Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive pembrolizumab (as monotherapy or in combination with canakinumab).
    End point values
    		 Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    34
    17
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 predose
    0 ( 0 )
    0 ( 0 )
        Cyle 1 0.5 hours post dose
    65.5 ( 23.8 )
    65.5 ( 19.9 )
        Cycle 2 predose
    16.0 ( 43.4 )
    35.5 ( 13.7 )
    No statistical analyses for this end point

    Secondary: Major Pathological Response (MPR) rate at the time of surgery in subjects randomized to pembrolizumab monotherapy based on central review

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    End point title
    		 Major Pathological Response (MPR) rate at the time of surgery in subjects randomized to pembrolizumab monotherapy based on central review [9]
    End point description
    MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects randomized to pembrolizumab monotherapy arm based on central review.
    End point type
    Secondary
    End point timeframe
    At time of surgery (up to 6 weeks after first dose)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive pembrolizumab monotherapy
    End point values
    		 Pembrolizumab monotherapy
    Number of subjects analysed
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    16.7 (3.58 to 41.42)
    No statistical analyses for this end point

    Secondary: Difference in Major Pathological Response (MPR) rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review

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    End point title
    		 Difference in Major Pathological Response (MPR) rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review [10]
    End point description
    MPR was defined as the percentage of participants with ≤10% residual viable tumor cells on surgical samples. MPR was assessed at the time of surgery based on central review. The difference in MPR rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review along with the Chang and Zhang confidence interval was assessed.
    End point type
    Secondary
    End point timeframe
    At time of surgery (up to 6 weeks after first dose of study treatment)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint specifically pertains to subjects who were randomized to receive pembrolizumab monotherapy or canakinumab in combination with pembrolizumab.
    End point values
    		 Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    17.1 (6.56 to 33.65)
    16.7 (3.58 to 41.42)
    Statistical analysis title
    		 Difference in MPR rate
    Comparison groups
    Pembrolizumab monotherapy v Canakinumab + pembrolizumab
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.56
         upper limit
    		 21.23

    Secondary: Surgical feasibility rate

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    End point title
    		 Surgical feasibility rate
    End point description
    Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 6 weeks after first dose
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    35
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    91.4 (76.94 to 98.20)
    97.1 (85.08 to 99.93)
    100 (81.47 to 100.00)
    No statistical analyses for this end point

    Secondary: Major Pathological Response (MPR) rate at the time of surgery in all subjects based on local review

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    End point title
    		 Major Pathological Response (MPR) rate at the time of surgery in all subjects based on local review
    End point description
    MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects based on local review.
    End point type
    Secondary
    End point timeframe
    At time of surgery (up to 6 weeks after first dose)
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    35
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.00 to 10.00)
    20.0 (8.44 to 36.94)
    22.2 (6.41 to 47.64)
    No statistical analyses for this end point

    Secondary: Major Pathological Response (MPR) rate based on the levels of biomarkers

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    End point title
    		 Major Pathological Response (MPR) rate based on the levels of biomarkers
    End point description
    MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR rate was analyzed by the biomarker subgroups at baseline. Biomarkers included PD-L1, CD8, hs-CRP and hs-IL-6.
    End point type
    Secondary
    End point timeframe
    From date of randomization up to 6 weeks after first dose
    End point values
    		 Canakinumab monotherapy Canakinumab + pembrolizumab Pembrolizumab monotherapy
    Number of subjects analysed
    35
    35
    18
    Units: Percentage of participants
    number (confidence interval 95%)
        PD-L1: <1%
    0 (0.00 to 26.46)
    7.1 (0.18 to 33.87)
    14.3 (0.36 to 57.87)
        PD-L1: 1-49%
    6.7 (0.17 to 31.95)
    15.4 (1.92 to 45.45)
    16.7 (0.42 to 64.12)
        PD-L1: >=50%
    0 (0.00 to 45.93)
    42.9 (9.90 to 81.59)
    0 (0.00 to 70.76)
        hs-CRP: <2mg/L
    12.5 (0.32 to 52.65)
    7.7 (0.19 to 36.03)
    37.5 (8.52 to 75.51)
        hs-CRP: >=2mg/L
    0 (0.0 to 13.23)
    22.7 (7.82 to 45.37)
    0 (0.00 to 33.63)
        hs-IL-6: <Q1 (2.52 mg/L)
    16.7 (0.42 to 64.12)
    12.5 (0.32 to 52.65)
    14.3 (0.36 to 57.87)
        hs-IL-6: >=Q1 (2.52 pg/mL) to <Q2 (5.36 pg/mL)
    0 (0.00 to 36.94)
    10 (0.25 to 44.50)
    33.3 (0.84 to 90.57)
        hs-IL-6: >=Q2 (5.36 pg/mL) to <Q3 (12.03 pg/mL)
    0 (0.00 to 36.94)
    28.6 (3.67 to 70.96)
    16.7 (0.42 to 64.12)
        hs-IL-6: >=Q3 (12.03 pg/mL)
    0 (0.00 to 30.85)
    20.0 (2.52 to 55.61)
    0 (0.00 to 97.50)
        CD8: <3%
    0 (0.00 to 26.46)
    13.0 (2.78 to 33.59)
    0 (0.00 to 52.18)
        CD8: >=3%
    0 (0.00 to 18.53)
    22.2 (2.81 to 60.01)
    33.3 (4.33 to 77.72)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From day of first dose of study medication to 130 days after last dose of study medication, up to 25.6 weeks
    Adverse event reporting additional description
    Any sign or symptom that occurs during the study treatment plus the 130 days post treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Canakinumab monotherapy
    Reporting group description
    		 Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Pembrolizumab monotherapy
    Reporting group description
    		 Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Reporting group title
    Canakinumab + pembrolizumab
    Reporting group description
    		 Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

    Serious adverse events
    		 Canakinumab monotherapy Pembrolizumab monotherapy Canakinumab + pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 35 (28.57%)
    4 / 18 (22.22%)
    9 / 35 (25.71%)
         number of deaths (all causes)
    3
    1
    2
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Procedural pain
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Postoperative respiratory failure
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Myocardial ischaemia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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 failure
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Gastrointestinal disorders
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (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
    Hepatobiliary disorders
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Dyspnoea
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (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
    Pleural effusion
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Pneumothorax
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Skin and subcutaneous tissue disorders
    Subcutaneous emphysema
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (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
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    3 / 35 (8.57%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyopneumothorax
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Infectious pleural effusion
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    COVID-19
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    0 / 35 (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
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Canakinumab monotherapy Pembrolizumab monotherapy Canakinumab + pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 35 (80.00%)
    14 / 18 (77.78%)
    27 / 35 (77.14%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    1
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    2
    1
    2
    Chest pain
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    2
    1
    2
    Fatigue
         subjects affected / exposed
    9 / 35 (25.71%)
    4 / 18 (22.22%)
    5 / 35 (14.29%)
         occurrences all number
    9
    4
    5
    Influenza like illness
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    0
    Pain
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    1
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 35 (11.43%)
    1 / 18 (5.56%)
    6 / 35 (17.14%)
         occurrences all number
    4
    1
    6
    Dysphonia
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    1
    1
    2
    Cough
         subjects affected / exposed
    4 / 35 (11.43%)
    2 / 18 (11.11%)
    6 / 35 (17.14%)
         occurrences all number
    5
    2
    6
    Productive cough
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    2
    0
    1
    Haemoptysis
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 18 (11.11%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    0
    1
    2
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    4 / 35 (11.43%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    5
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    2
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    2
    1
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    2
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    2
    1
    2
    Lipase increased
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    2
    1
    1
    Lymphocyte count decreased
         subjects affected / exposed
    4 / 35 (11.43%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    5
    1
    0
    SARS-CoV-2 test negative
         subjects affected / exposed
    2 / 35 (5.71%)
    3 / 18 (16.67%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    3
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 35 (2.86%)
    2 / 18 (11.11%)
    3 / 35 (8.57%)
         occurrences all number
    1
    2
    3
    Amylase increased
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    3
    1
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    1
    0
    3
    Bilirubin conjugated increased
         subjects affected / exposed
    4 / 35 (11.43%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    4
    1
    1
    SARS-CoV-2 test positive
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    2
    1
    1
    Weight decreased
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    1
    White blood cell count decreased
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    0
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 18 (11.11%)
    6 / 35 (17.14%)
         occurrences all number
    0
    2
    6
    Wound complication
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 35 (2.86%)
    2 / 18 (11.11%)
    1 / 35 (2.86%)
         occurrences all number
    1
    2
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    1
    0
    2
    Dysgeusia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    2 / 35 (5.71%)
         occurrences all number
    0
    1
    2
    Dizziness
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 35 (25.71%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    10
    1
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Constipation
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    3 / 35 (8.57%)
         occurrences all number
    2
    1
    3
    Diarrhoea
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 18 (0.00%)
    6 / 35 (17.14%)
         occurrences all number
    3
    0
    7
    Dry mouth
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 18 (11.11%)
    1 / 35 (2.86%)
         occurrences all number
    0
    2
    1
    Nausea
         subjects affected / exposed
    4 / 35 (11.43%)
    3 / 18 (16.67%)
    3 / 35 (8.57%)
         occurrences all number
    7
    3
    3
    Vomiting
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    2
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    Ecchymosis
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    4 / 35 (11.43%)
         occurrences all number
    1
    1
    4
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    5 / 35 (14.29%)
         occurrences all number
    0
    1
    5
    Hypothyroidism
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    3 / 35 (8.57%)
         occurrences all number
    0
    1
    3
    Musculoskeletal and connective tissue disorders
    Polyarthritis
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    1
    Myalgia
         subjects affected / exposed
    0 / 35 (0.00%)
    0 / 18 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    0
    0
    3
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    1
    Arthralgia
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    1
    Infections and infestations
    Enterocolitis infectious
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Erysipelas
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 18 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    0
    Post procedural infection
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Rash pustular
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Wound infection
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 35 (17.14%)
    0 / 18 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    6
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 18 (5.56%)
    4 / 35 (11.43%)
         occurrences all number
    1
    1
    4
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 18 (5.56%)
    0 / 35 (0.00%)
         occurrences all number
    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
    07 Apr 2020
    The main rationale for this amendment was to implement the request from the Health Authority to modify the target population for Major Pathological Response (MPR) from “evaluable subjects” to “randomized subjects”. Changes to inclusion/exclusion criteria were made to allow for more clarity and flexibility for the enrollment/randomization. The EOT visit window was changed to within 21 days after the permanent discontinuation of study treatment but before the surgery to provide more flexibility to the site and patient. The surgery-related safety was added as an exploratory objective.

    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
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    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
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