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    Clinical Trial Results:
    A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib and spartalizumab vs capmatinib and placebo as 1st line treatment for advanced NSCLC patients with MET exon14 skipping mutations

    Summary
    EudraCT number
    		 2019-003097-11
    Trial protocol
    		 DE   FR   BE   IT  
    Global end of trial date
    26 Jan 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    22 Feb 2024
    First version publication date
    16 Dec 2023
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    CINC280J12201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04323436
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis, 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
    26 Jan 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jan 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives of the trial were: • Run-in part: To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab • Randomized part: To compare the efficacy of capmatinib in combination with spartalizumab versus capmatinib plus placebo
    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
    19 Aug 2020
    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: 8
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Japan: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    31
    EEA total number of subjects
    24
    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)
    6
    From 65 to 84 years
    24
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in 15 investigative sites in 9 countries.

    Pre-assignment
    Screening details
    		 Screening evaluations were performed within 28 days prior to the first dose of study treatment. The study enrollment was halted during the Run-in part per sponsor's decision. Following the study enrollment halt, spartalizumab treatment was discontinued and the Randomized part was not initiated.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    The run-in part (part 1) was open label. The randomized part (part 2) was not initiated.

    Arms
    Arm title
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Arm description
    		 Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab 400 mg intravenously every 28 days (Q4W) in the run-in part.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spartalizumab
    Investigational medicinal product code
    PDR001
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Spartalizumab 400 mg intravenously every 28 days (Q4W)

    Investigational medicinal product name
    Capmatinib
    Investigational medicinal product code
    INC280
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Capmatinib 400 mg orally twice daily (BID)

    Number of subjects in period 1
    		Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Started
    31
    Treated with capmatinib + spartalizumab
    28
    Treated with capmatinib only
    3
    Completed
    0
    Not completed
    31
         Physician decision
    2
         Subject decision
    3
         Transfer to another study or alternative treatment
    8
         Death
    1
         Adverse event
    7
         Progressive disease
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Reporting group description
    		 Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab 400 mg intravenously every 28 days (Q4W) in the run-in part.

    Reporting group values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W Total
    Number of subjects
    		 31 31
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 6 6
        From 65-84 years
    		 24 24
        85 years and over
    		 1 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 71.6 ± 9.50 -
    Sex: Female, Male
    Units: participants
        Female
    		 16 16
        Male
    		 15 15
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 23 23
        Black or African American
    		 1 1
        Asian
    		 6 6
        Unknown
    		 1 1

    End points

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    End points reporting groups
    Reporting group title
    Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Reporting group description
    		 Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab 400 mg intravenously every 28 days (Q4W) in the run-in part.

    Primary: Randomized part: Progression-Free Survival (PFS) by BIRC as per RECIST 1.1

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    End point title
    		 Randomized part: Progression-Free Survival (PFS) by BIRC as per RECIST 1.1 [1]
    End point description
    PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on blinded independent review committee (BIRC) assessment per RECIST v1.1.
    End point type
    Primary
    End point timeframe
    Up to 6 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The randomized part of the study was not initiated.
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Primary: Run-in part: Overall Response Rate (ORR) by investigator assessment as per RECIST 1.1

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    End point title
    		 Run-in part: Overall Response Rate (ORR) by investigator assessment as per RECIST 1.1 [2]
    End point description
    Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, 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
    Primary
    End point timeframe
    Up to approximately 2 years and 4 months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were planned for this endpoint
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    31
    Units: percentage of participants
        number (confidence interval 95%)
    35.5 (19.2 to 54.6)
    No statistical analyses for this end point

    Secondary: Run-in part: Disease Control Rate (DCR) by investigator assessment as per RECIST 1.1

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    End point title
    		 Run-in part: Disease Control Rate (DCR) by investigator assessment as per RECIST 1.1
    End point description
    DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response was based on local investigator assessment per RECIST v1.1. For RECIST v1.1, 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; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression).
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years and 4 months
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    31
    Units: percentage of participants
        number (confidence interval 95%)
    77.4 (58.9 to 90.4)
    No statistical analyses for this end point

    Secondary: Run-in part: Dose intensity of capmatinib

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    End point title
    		 Run-in part: Dose intensity of capmatinib
    End point description
    Dose intensity of capmatinib was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.
    End point type
    Secondary
    End point timeframe
    From first dose of capmatinib to last dose, up to 2.4 years
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    31
    Units: mg/day
        arithmetic mean (standard deviation)
    595.9 ± 173.6
    No statistical analyses for this end point

    Secondary: Run-in part: Dose intensity of spartalizumab

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    End point title
    		 Run-in part: Dose intensity of spartalizumab
    End point description
    Dose intensity of spartalizumab was calculated as actual cumulative dose in milligrams divided by duration of exposure in days and then multiplied by the duration of one cycle (28 days).
    End point type
    Secondary
    End point timeframe
    From first dose of spartalizumab to last dose, up to 0.9 years
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    28
    Units: mg/cycle
        arithmetic mean (standard deviation)
    365.6 ± 51.5
    No statistical analyses for this end point

    Secondary: Run-in part: Number of participants with dose reductions and dose interruptions of spartalizumab

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    End point title
    		 Run-in part: Number of participants with dose reductions and dose interruptions of spartalizumab
    End point description
    Number of participants with at least one dose reduction of spartalizumab and number of participants with at least one dose interruption of spartalizumab. Dose reductions were not allowed for spartalizumab.
    End point type
    Secondary
    End point timeframe
    From first dose of spartalizumab to last dose, up to 0.9 years
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    28
    Units: participants
        At least one dose reduction
    0
        At least one dose interruption
    7
    No statistical analyses for this end point

    Secondary: Run-in part: Number of participants with dose reductions and dose interruptions of capmatinib

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    End point title
    		 Run-in part: Number of participants with dose reductions and dose interruptions of capmatinib
    End point description
    Number of participants with at least one dose reduction of capmatinib and number of participants with at least one dose interruption of capmatinib.
    End point type
    Secondary
    End point timeframe
    From first dose of capmatinib to last dose, up to 2.4 years
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    31
    Units: participants
        At least one dose reduction
    19
        At least one dose interruption
    20
    No statistical analyses for this end point

    Secondary: Run-in part: Time to reach maximum plasma concentration (Tmax) of capmatinib

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    End point title
    		 Run-in part: Time to reach maximum plasma concentration (Tmax) of capmatinib
    End point description
    PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
    End point type
    Secondary
    End point timeframe
    pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    7
    Units: hours
        median (full range (min-max))
    1.75 (1.00 to 3.92)
    No statistical analyses for this end point

    Secondary: Run-in part: Maximum observed plasma concentration (Cmax) of capmatinib

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    End point title
    		 Run-in part: Maximum observed plasma concentration (Cmax) of capmatinib
    End point description
    Pharmacokinetic (PK) parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
    End point type
    Secondary
    End point timeframe
    pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    7
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    2730 ± 74.3
    No statistical analyses for this end point

    Secondary: Run-in part: Area under the plasma concentration-time curve from time zero to the end of a dosing interval (AUCtau) of capmatinib

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    End point title
    		 Run-in part: Area under the plasma concentration-time curve from time zero to the end of a dosing interval (AUCtau) of capmatinib
    End point description
    PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 12 hours. The portion of area under the curve between 8 hours and 12 hours post-dose was calculated by extrapolation based on terminal elimination slop.
    End point type
    Secondary
    End point timeframe
    pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    3
    Units: hr*ng/mL
        geometric mean (geometric coefficient of variation)
    12900 ± 96.1
    No statistical analyses for this end point

    Secondary: Run-in part: Progression-Free Survival (PFS) by investigator assessment as per RECIST 1.1

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    End point title
    		 Run-in part: Progression-Free Survival (PFS) by investigator assessment as per RECIST 1.1
    End point description
    PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on investigator assessment per RECIST v1.1. Progression is defined using RECIST v1.1 as at least 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years and 5 months
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    31
    Units: months
        median (confidence interval 95%)
    16.5 (7.4 to 999)
    No statistical analyses for this end point

    Secondary: Run-in part: Maximum observed serum concentration (Cmax) of spartalizumab

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    End point title
    		 Run-in part: Maximum observed serum concentration (Cmax) of spartalizumab
    End point description
    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
    End point type
    Secondary
    End point timeframe
    pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    9
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    135 ± 28.4
    No statistical analyses for this end point

    Secondary: Run-in part: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of capmatinib

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    End point title
    		 Run-in part: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of capmatinib
    End point description
    PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
    End point type
    Secondary
    End point timeframe
    pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    7
    Units: hr*ng/mL
        geometric mean (geometric coefficient of variation)
    10000 ± 61.8
    No statistical analyses for this end point

    Secondary: Run-in part: Area under the serum concentration-time curve from time zero to the end of a dosing interval (AUCtau) of spartalizumab

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    End point title
    		 Run-in part: Area under the serum concentration-time curve from time zero to the end of a dosing interval (AUCtau) of spartalizumab
    End point description
    PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 28 days.
    End point type
    Secondary
    End point timeframe
    pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    8
    Units: hr*µg/mL
        geometric mean (geometric coefficient of variation)
    49700 ± 47.8
    No statistical analyses for this end point

    Secondary: Run-in part: Time to reach maximum serum concentration (Tmax) of spartalizumab

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    End point title
    		 Run-in part: Time to reach maximum serum concentration (Tmax) of spartalizumab
    End point description
    PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
    End point type
    Secondary
    End point timeframe
    pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    9
    Units: hours
        median (full range (min-max))
    1.67 (0.917 to 164)
    No statistical analyses for this end point

    Secondary: Randomized part: Overall Survival (OS)

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    End point title
    		 Randomized part: Overall Survival (OS)
    End point description
    OS is defined as the time from date of start of treatment to date of death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 12 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Dose intensity of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Dose intensity of capmatinib and spartalizumab
    End point description
    Dose intensity is defined as the ratio of actual cumulative dose and duration of exposure.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: mg/day
        arithmetic mean (standard deviation)
    No statistical analyses for this end point

    Secondary: Randomized part: Number of participants with dose reductions and dose interruptions of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Number of participants with dose reductions and dose interruptions of capmatinib and spartalizumab
    End point description
    Number of participants with at least one dose reduction of capmatinib and spartalizumab and number of participants with at least one dose interruption of capmatinib and spartalizumab.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: participants
    No statistical analyses for this end point

    Secondary: Run-in part: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of spartalizumab

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    End point title
    		 Run-in part: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of spartalizumab
    End point description
    PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
    End point type
    Secondary
    End point timeframe
    pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
    End point values
    		 Run-in part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W
    Number of subjects analysed
    9
    Units: hr*µg/mL
        geometric mean (geometric coefficient of variation)
    52900 ± 64.6
    No statistical analyses for this end point

    Secondary: Randomized part: Progression-Free Survival (PFS) by investigator assessment as per RECIST 1.1

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    End point title
    		 Randomized part: Progression-Free Survival (PFS) by investigator assessment as per RECIST 1.1
    End point description
    PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on investigator assessment per RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Overall Response Rate (ORR) by BIRC and investigator assessment as per RECIST 1.1

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    End point title
    		 Randomized part: Overall Response Rate (ORR) by BIRC and investigator assessment as per RECIST 1.1
    End point description
    ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) and Partial Response (PR). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: percentage of participants
        number (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Disease Control Rate (DCR) by BIRC and investigator assessment as per RECIST 1.1

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    End point title
    		 Randomized part: Disease Control Rate (DCR) by BIRC and investigator assessment as per RECIST 1.1
    End point description
    DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: percentage of participants
        number (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Duration of Response (DOR) by BIRC and investigator assessment as per RECIST 1.1

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    End point title
    		 Randomized part: Duration of Response (DOR) by BIRC and investigator assessment as per RECIST 1.1
    End point description
    DOR is defined as the time from the date of first documented response (CR or PR) to the first documented progression per RECIST 1.1 or death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Change from baseline in EORTC QLQ-LC13

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    End point title
    		 Randomized part: Change from baseline in EORTC QLQ-LC13
    End point description
    EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from “not at all” to “very much”. Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: score on scale
        arithmetic mean (standard deviation)
    No statistical analyses for this end point

    Secondary: Randomized part: Change from baseline in EORTC QLQ-C30

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    End point title
    		 Randomized part: Change from baseline in EORTC QLQ-C30
    End point description
    The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden. The QLQ‐C30 summary score (0-100) is calculated as the mean of 13 of the 15 QLQ‐C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better health-related QoL.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: score on scale
        arithmetic mean (standard deviation)
    No statistical analyses for this end point

    Secondary: Randomized part: Change from baseline in EQ-5D-5L

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    End point title
    		 Randomized part: Change from baseline in EQ-5D-5L
    End point description
    The EQ-5D-5L is a standardized measure of health utility that provides a single index value for one’s health status. The EQ-5D-5L contains one item for each of five dimensions of health-related quality of life (HRQOL) (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Response options for each item vary from having no problems to extreme problems. Subject responses to the five dimensions of HRQOL reflect a specific health state that corresponds to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). A visual analog scale (ranging from 0 to 100) is also included to capture subject’s rating of their overall health status. Higher scores of the EQ-5D-5L represent better health states.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: score on scale
        arithmetic mean (standard deviation)
    No statistical analyses for this end point

    Secondary: Randomized part: Time to response (TTR) by BIRC and investigator assessment as per RECIST 1.1

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    End point title
    		 Randomized part: Time to response (TTR) by BIRC and investigator assessment as per RECIST 1.1
    End point description
    TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed, according to RECIST 1.1.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Maximum observed concentration (Cmax) of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Maximum observed concentration (Cmax) of capmatinib and spartalizumab
    End point description
    Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    No statistical analyses for this end point

    Secondary: Randomized part: Time to reach maximum concentration (Tmax) of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Time to reach maximum concentration (Tmax) of capmatinib and spartalizumab
    End point description
    Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) concentration following a dose.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: hours
        median (full range (min-max))
    No statistical analyses for this end point

    Secondary: Randomized part: Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire

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    End point title
    		 Randomized part: Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire
    End point description
    EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain in chest, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from “not at all” to “very much”. Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms. The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Time to definitive deterioration in global health status/QoL, shortness of breath and pain per EORTC QLQ-C30

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    End point title
    		 Randomized part: Time to definitive deterioration in global health status/QoL, shortness of breath and pain per EORTC QLQ-C30
    End point description
    The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden. The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: months
        median (confidence interval 95%)
    No statistical analyses for this end point

    Secondary: Randomized part: Area under the concentration-time curve from time zero to the end of a dosing interval (AUCtau) of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Area under the concentration-time curve from time zero to the end of a dosing interval (AUCtau) of capmatinib and spartalizumab
    End point description
    Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: hr*ng/mL
        geometric mean (geometric coefficient of variation)
    No statistical analyses for this end point

    Secondary: Randomized part: Number of participants with anti-spartalizumab antibodies

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    End point title
    		 Randomized part: Number of participants with anti-spartalizumab antibodies
    End point description
    Immunogenicity (IG) evaluated in serum samples. The assay to quantify and assess the IG was a validated homogeneous enzyme-linked immunosorbent assay (ELISA).
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose), up to 6 years
    End point values
    Number of subjects analysed
    Units: participants
    No statistical analyses for this end point

    Secondary: Randomized part: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of capmatinib and spartalizumab

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    End point title
    		 Randomized part: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of capmatinib and spartalizumab
    End point description
    Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods.
    End point type
    Secondary
    End point timeframe
    Up to 6 years
    End point values
    Number of subjects analysed
    Units: hr*ng/mL
        geometric mean (geometric coefficient of variation)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of spartalizumab+capmatinib (or capmatinib single agent for patients who did not receive spartalizumab) to 150 days after last dose of spartalizumab or 30 days after last dose of capmatinib, whichever was longer, up to 2 years and 5 months
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Capmatinib + Spartalizumab (Prior discontinuing spartalizumab)
    Reporting group description
    		 Run-in part. Capmatinib 400 mg BID in combination with spartalizumab 400 mg Q4W before the discontinuation of spartalizumab

    Reporting group title
    Capmatinib only
    Reporting group description
    		 Run-in part. Immediately following the discontinuation of spartalizumab (and enrollment halt), enrolled subjects who had not started study treatment received capmatinib single agent treatment from the start

    Reporting group title
    Capmatinib + Spartalizumab (After discontinuing spartalizumab)
    Reporting group description
    		 Run-in part. Capmatinib 400 mg BID in combination with spartalizumab 400 mg Q4W after the discontinuation of spartalizumab

    Serious adverse events
    		 Capmatinib + Spartalizumab (Prior discontinuing spartalizumab) Capmatinib only Capmatinib + Spartalizumab (After discontinuing spartalizumab)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 28 (39.29%)
    1 / 3 (33.33%)
    8 / 28 (28.57%)
         number of deaths (all causes)
    4
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Inferior vena cava syndrome
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    Encephalopathy
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (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
    Oedema peripheral
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (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
    Oedema
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device site haemorrhage
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatotoxicity
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    Drug-induced liver injury
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Osteomyelitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    Pneumonia
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    0 / 28 (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
    Clostridium colitis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         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 tract infection
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (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
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 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
    		 Capmatinib + Spartalizumab (Prior discontinuing spartalizumab) Capmatinib only Capmatinib + Spartalizumab (After discontinuing spartalizumab)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 28 (89.29%)
    3 / 3 (100.00%)
    18 / 28 (64.29%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    3
    Hypertension
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    1
    1
    1
    Chest pain
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    2
    3
    1
    Face oedema
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    0
    0
    Fatigue
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 3 (33.33%)
    3 / 28 (10.71%)
         occurrences all number
    3
    1
    6
    Oedema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    4 / 28 (14.29%)
         occurrences all number
    1
    0
    5
    Oedema peripheral
         subjects affected / exposed
    11 / 28 (39.29%)
    3 / 3 (100.00%)
    15 / 28 (53.57%)
         occurrences all number
    13
    12
    19
    Pyrexia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Swelling
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    Scrotal oedema
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 3 (66.67%)
    4 / 28 (14.29%)
         occurrences all number
    1
    2
    5
    Cough
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    3
    Asphyxia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Pneumonitis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    2
    Confusional state
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 28 (28.57%)
    1 / 3 (33.33%)
    6 / 28 (21.43%)
         occurrences all number
    11
    1
    4
    Amylase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 3 (0.00%)
    4 / 28 (14.29%)
         occurrences all number
    3
    0
    7
    Aspartate aminotransferase increased
         subjects affected / exposed
    9 / 28 (32.14%)
    1 / 3 (33.33%)
    6 / 28 (21.43%)
         occurrences all number
    13
    2
    10
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    1
    1
    2
    Blood bilirubin increased
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    5
    1
    2
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    4 / 28 (14.29%)
         occurrences all number
    1
    0
    4
    Blood creatinine increased
         subjects affected / exposed
    10 / 28 (35.71%)
    2 / 3 (66.67%)
    11 / 28 (39.29%)
         occurrences all number
    15
    2
    22
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    2
    1
    1
    Lipase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 3 (33.33%)
    5 / 28 (17.86%)
         occurrences all number
    3
    2
    8
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Platelet count decreased
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Weight decreased
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    3
    1
    0
    Weight increased
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    4 / 28 (14.29%)
         occurrences all number
    2
    1
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    3
    1
    2
    Dizziness
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    3
    1
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    2
    2
    1
    Anaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    1
    0
    3
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    8 / 28 (28.57%)
    2 / 3 (66.67%)
    1 / 28 (3.57%)
         occurrences all number
    8
    3
    1
    Diarrhoea
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    5 / 28 (17.86%)
         occurrences all number
    0
    3
    6
    Vomiting
         subjects affected / exposed
    5 / 28 (17.86%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    5
    0
    0
    Nausea
         subjects affected / exposed
    9 / 28 (32.14%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    11
    1
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    1
    1
    1
    Gastritis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    2
    0
    2
    Dry mouth
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Stomatitis
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    4 / 28 (14.29%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    4
    1
    1
    Pruritus
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Dermatitis acneiform
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Alopecia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Rash
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    4 / 28 (14.29%)
         occurrences all number
    1
    0
    6
    Arthralgia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    3
    0
    2
    Back pain
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    2
    1
    2
    Muscle spasms
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    Infections and infestations
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 3 (66.67%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 3 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    3
    Respiratory tract infection
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 3 (33.33%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 3 (66.67%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 28 (14.29%)
    1 / 3 (33.33%)
    2 / 28 (7.14%)
         occurrences all number
    4
    2
    5
    Hyperkalaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 3 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 3 (66.67%)
    5 / 28 (17.86%)
         occurrences all number
    1
    2
    10
    Hypokalaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    3
    Hyponatraemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 3 (0.00%)
    3 / 28 (10.71%)
         occurrences all number
    1
    0
    3
    Hypophosphataemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 3 (33.33%)
    1 / 28 (3.57%)
         occurrences all number
    0
    4
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Oct 2021
    The main purpose of this protocol amendment was to modify the study conduct and data analysis following the sponsor’s decision to halt study enrollment on 28-Jul-2021, as communicated to Health Authorities as per local requirements. The enrollment halt decision was based on lack of tolerability observed in capmatinib and spartalizumab combination treatment arm in the Part 1 of the trial. Immediately following the enrollment halt, below procedural changes were performed: • All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib, given the proven tolerability and efficacy of capmatinib monotherapy in this study indication. • Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start. In addition, blinded and independent centralized tumor assessment was no longer required. Updates in several sections were implemented.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/#/
    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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