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    Clinical Trial Results:
    A phase III randomized, controlled, open-label, multicenter, global study of capmatinib in combination with osimertinib versus platinum - pemetrexed based doublet chemotherapy in patients with locally advanced or metastatic NSCLC harboring EGFR activating mutations who have progressed on prior EGFR‑TKI therapy and whose tumors are T790M mutation negative and harbor MET amplification (GEOMETRY-E)

    Summary
    EudraCT number
    		 2020-003677-21
    Trial protocol
    		 DE   ES   SI   PL   IT   BG   HU   HR  
    Global end of trial date
    27 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Oct 2023
    First version publication date
    20 Oct 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CINC280L12301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04816214
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Study Director, Novartis, +41 6133241111, novartis.email@novartis.com
    Scientific contact
    Study Director, Novartis, +41 6133241111, 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
    27 Dec 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Dec 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The study aimed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR mutation, T790M negative, MET amplified, who progressed following EGFR tyrosine kinase inhibitors (TKIs). A run-in part was conducted to determine the recommended dose of capmatinib and osimertinib for the randomized part. On 11-May-2022, Novartis decided to halt enrollment for this study due to a business consideration unrelated to any safety concerns. Ongoing patients in the run-in part were allowed to continue treatment through other post-trial drug supply options, as applicable. On 27-Dec-2022 the last patient was transitioned off the study, and following the study protocol this date was declared the Global end of trial date. Randomized part was not initiated.
    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
    22 Sep 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 2
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Worldwide total number of subjects
    6
    EEA total number of subjects
    0
    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)
    4
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 In the Run-in part, subjects were enrolled at 4 investigative sites in 3 countries. The study was terminated early based on Sponsor's decision unrelated to safety concerns and the randomized part of the study was not initiated.

    Pre-assignment
    Screening details
    		 A total of 23 subjects were screened of which 6 subjects were enrolled in the run-in part of the study.

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

    Arms
    Arm title
    		 Run-in Part: Capmatinib + Osimertinib
    Arm description
    		 Subjects received a starting dose of capmatinib 400 mg, orally, twice daily (BID) in combination with osimertinib 80 mg, orally, once daily (QD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Capmatinib
    Investigational medicinal product code
    Other name
    INC280
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg of capmatinib administered BID

    Investigational medicinal product name
    Osimertinib
    Investigational medicinal product code
    Other name
    Tagrisso, Tagrix
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    80 mg of osimertinib administered QD

    Number of subjects in period 1
    		Run-in Part: Capmatinib + Osimertinib
    Started
    6
    Completed
    0
    Not completed
    6
         Death
    1
         Progressive Disease
    4
         Study Terminated by Sponsor
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Run-in Part: Capmatinib + Osimertinib
    Reporting group description
    		 Subjects received a starting dose of capmatinib 400 mg, orally, twice daily (BID) in combination with osimertinib 80 mg, orally, once daily (QD)

    Reporting group values
    		 Run-in Part: Capmatinib + Osimertinib Total
    Number of subjects
    		 6 6
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.7 ± 7.76 -
    Gender categorical
    Units: Subjects
        Female
    		 4 4
        Male
    		 2 2
    Race
    Units: Subjects
        Asian
    		 6 6

    End points

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    End points reporting groups
    Reporting group title
    Run-in Part: Capmatinib + Osimertinib
    Reporting group description
    		 Subjects received a starting dose of capmatinib 400 mg, orally, twice daily (BID) in combination with osimertinib 80 mg, orally, once daily (QD)

    Primary: Run-in Part: Number of Partipants With Dose Limiting Toxicities (DLTs)

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    End point title
    		 Run-in Part: Number of Partipants With Dose Limiting Toxicities (DLTs) [1]
    End point description
    A DLT was defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, progressive disease, inter-current illness, or concomitant medications, that despite optimal therapeutic intervention that occurred within the first 21 days of treatment with capmatinib in combination with osimertinib. FAS included all participants who received any component of the study treatment.
    End point type
    Primary
    End point timeframe
    Up to 21 Days (3 weeks)
    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: Only descriptive statistical analysis was planned to be reported for this endpoint.
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: subjects
    0
    No statistical analyses for this end point

    Secondary: Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug

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    End point title
    		 Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug
    End point description
    Number of participants with at least one dose interruption and dose reduction were reported for each study drug. Safety set included all participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From the first dose until last dose of study treatment, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: subjects
        Dose Interruption: Capmatinib
    5
        Dose Interruption: Osimertinib
    4
        Dose Reduction: Capmatinib
    3
        Dose Reduction: Osimertinib
    0
    No statistical analyses for this end point

    Secondary: Run-in Part: Dose Intensity of Each Study Drug

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    End point title
    		 Run-in Part: Dose Intensity of Each Study Drug
    End point description
    Dose intensity was computed as the ratio of actual cumulative dose (milligrams) received and actual duration of exposure (weeks) to study drug. Safety set included all participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From the first dose until last dose of study treatment, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: milligrams per week (mg/week)
    arithmetic mean (standard deviation)
        Capmatinib
    5042.8 ± 947.28
        Osimertinib
    534.9 ± 41.29
    No statistical analyses for this end point

    Secondary: Run-in Part: Median Duration of Exposure to Each Study Drug

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    End point title
    		 Run-in Part: Median Duration of Exposure to Each Study Drug
    End point description
    Duration of exposure is defined as the time (in weeks) between the first and the last dose of study treatment. Safety set included all participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From the first dose until last dose of study treatment, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: weeks
    median (full range (min-max))
        Capmatinib
    23.5 (1 to 39)
        Osimertinib
    24.0 (1 to 39)
    No statistical analyses for this end point

    Secondary: Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib

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    End point title
    		 Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib
    End point description
    Blood samples were collected. Cmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. PK analysis set included all participants who provided at least one evaluable PK concentration. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Day 1 (n=6)
    5510 ± 2380
        Day 15 (n=5)
    5750 ± 1050
    No statistical analyses for this end point

    Secondary: Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

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    End point title
    		 Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
    End point description
    Blood samples were colllected. Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. PK analysis set included all participants who provided at least one evaluable PK concentration. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    5
    Units: ng/mL
    arithmetic mean (standard deviation)
        Osimertinib: Day 1 (n=5)
    99.5 ± 57.0
        Osimertinib: Day 15 (n=5)
    265 ± 113
        AZ5104: Day 1 (n=5)
    4.86 ± 3.22
        AZ5104: Day 15 (n=5)
    22.0 ± 9.23
        AZ7550: Day 1 (n=5)
    3.61 ± 1.53
        AZ7550: Day 15 (n=4)
    33.0 ± 11.9
    No statistical analyses for this end point

    Secondary: Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib

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    End point title
    		 Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib
    End point description
    Blood samples were colllected. Tmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. Actual recorded sampling times were considered for the calculations. PK analysis set included all participants who provided at least one evaluable PK concentration. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: hours
    median (full range (min-max))
        Day 1 (n=6)
    1.92 (0.983 to 3.021)
        Day 15 (n=5)
    1.00 (0.917 to 1.82)
    No statistical analyses for this end point

    Secondary: Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

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    End point title
    		 Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
    End point description
    Blood samples were collected. Tmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. Actual recorded sampling times were considered for the calculations. PK analysis set included all participants who provided at least one evaluable PK concentration. ‘Number of participants analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    5
    Units: hours
    median (full range (min-max))
        Osimertinib: Day 1 (n=5)
    6.00 (2.90 to 23.1)
        Osimertinib: Day 15 (n=5)
    4.00 (0.00 to 7.33)
        AZ5104: Day 1 (n=5)
    23.1 (22.3 to 23.5)
        AZ5104: Day 15 (n=5)
    4.00 (0.00 to 7.13)
        AZ7550: Day 1 (n=5)
    5.68 (2.90 to 23.1)
        AZ7550: Day 15 (n=4)
    2.25 (0.00 to 6.00)
    No statistical analyses for this end point

    Secondary: Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib

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    End point title
    		 Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib
    End point description
    Blood samples were collected. AUClast of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. PK analysis set included all participants who provided at least one evaluable PK concentration. ‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: nanograms*hours/milliliter (ng*hr/mL)
    arithmetic mean (standard deviation)
        Day 1 (n=6)
    20100 ± 6080
        Day 15 (n=5)
    21300 ± 7050
    No statistical analyses for this end point

    Secondary: Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

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    End point title
    		 Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
    End point description
    Blood samples were collected. AUClast of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. PK analysis set included all participants who provided at least one evaluable PK concentration.‘Number of subjects analysed’ indicates the number of participants with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of participants with data available at specified timepoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    5
    Units: ng*hr/mL
    arithmetic mean (standard deviation)
        Osimertinib: Day 1 (n=5)
    1790 ± 1030
        Osimertinib: Day 15 (n=5)
    1380 ± 900
        AZ5104: Day 1 (n=5)
    82.9 ± 59.4
        AZ5104: Day 15 (n=5)
    136 ± 56.8
        AZ7550: Day 1 (n=5)
    47.1 ± 46.3
        AZ7550: Day 15 (n=4)
    112 ± 111
    No statistical analyses for this end point

    Secondary: Run-in Part: Overall Response Rate (ORR) as per investigator assessment

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    End point title
    		 Run-in Part: Overall Response Rate (ORR) as per investigator assessment
    End point description
    ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator judgment and according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1). Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the sum of longest diameters (SLD) of the target lesions or no new lesions or no progression of non-target lesions. Full Analysis Set (FAS) included all participants who received any component of the study treatment.
    End point type
    Secondary
    End point timeframe
    Up to end of study, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: percentage of subjects
        number (confidence interval 95%)
    50.0 (11.8 to 88.2)
    No statistical analyses for this end point

    Secondary: Run-in Part: Duration of Response (DOR) as per investigator assessment

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    End point title
    		 Run-in Part: Duration of Response (DOR) as per investigator assessment
    End point description
    DOR was defined as the time from first documented response of CR or PR to the date of first documented progressive disease (PD) or death due to any cause. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions. FAS included all participants who received any component of the study treatment. ‘Number of subjects analysed’ indicates the number of participants with CR or PR. 9999= Upper limit of 95% confidence interval (CI) was not estimable due to an insufficient number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Up to disease progression or death or end of study, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    3
    Units: months
        median (confidence interval 95%)
    6.93 (2.50 to 9999)
    No statistical analyses for this end point

    Secondary: Run-in Part: Time to Response (TTR) as per investigator assessment

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    End point title
    		 Run-in Part: Time to Response (TTR) as per investigator assessment
    End point description
    TTR was defined as the duration of time between the date of first dose of treatment and the date of the first documented response of either CR or PR as per investigator judgment and according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions. FAS included all participants who received any component of the study treatment. ‘Number of subjects analysed’ indicates the number of participants with CR or PR. 9999= Median and the upper limit of 95% CI were not estimable due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From first dose of treatment up to end of study, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    3
    Units: months
        median (confidence interval 95%)
    9999 (1.41 to 9999)
    No statistical analyses for this end point

    Secondary: Run-in Part: Disease Control Rate (DCR) as per investigator assessment

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    End point title
    		 Run-in Part: Disease Control Rate (DCR) as per investigator assessment
    End point description
    DCR was defined as the percentage of participants with a BOR of CR, PR and stable disease (SD) as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. FAS included all participants who received any component of the study treatment.
    End point type
    Secondary
    End point timeframe
    From randomisation up to end of study, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: percentage of subjects
        number (confidence interval 95%)
    66.7 (22.3 to 95.7)
    No statistical analyses for this end point

    Secondary: Run-in Part: Progression-Free Survival (PFS) as per investigator assessment

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    End point title
    		 Run-in Part: Progression-Free Survival (PFS) as per investigator assessment
    End point description
    PFS was defined as the time (in months) from first dose of treatment to the date of the first documented PD or death due to any cause as per investigator judgment and according to RECIST v1.1. PFS was censored if no PFS event (progression or death) was observed. Progression was defined as a ≥20% increase in SLD compared to smallest SLD in the study, or progression of non-target lesions or new lesions. FAS included all participants who received any component of the study treatment. 9999= The upper limit of 95% CI was not estimable due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From first dose of treatment until first documented progression or death or end of study, assessed up to 39 weeks
    End point values
    		 Run-in Part: Capmatinib + Osimertinib
    Number of subjects analysed
    6
    Units: months
        median (confidence interval 95%)
    4.58 (0.99 to 9999)
    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 treatment until 30 days after last dose of study treatment, assessed up to 39 weeks
    Adverse event reporting additional description
    Safety set included all participants who received at least one dose of study treatment. Due to early study termination, the randomized part of the study was not conducted. Hence safety data was not collected in the randomized part of the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Run-in Part: Capmatinib + Osimertinib
    Reporting group description
    		 Subjects received a starting dose of capmatinib 400 mg, orally, BID in combination with osimertinib 80 mg, orally, QD for a maximum of 39 weeks.

    Serious adverse events
    		 Run-in Part: Capmatinib + Osimertinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 6 (33.33%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    COVID-19
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Run-in Part: Capmatinib + Osimertinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 6 (83.33%)
    General disorders and administration site conditions
    Peripheral swelling
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Oedema peripheral
         subjects affected / exposed
    4 / 6 (66.67%)
         occurrences all number
    5
    Fatigue
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Chills
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Investigations
    Lipase increased
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Amylase increased
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 6 (33.33%)
         occurrences all number
    4
    Diarrhoea
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    2
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Dry skin
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    3 / 6 (50.00%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Infections and infestations
    Paronychia
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    COVID-19
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 6 (50.00%)
         occurrences all number
    3
    Decreased appetite
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Sep 2021
    Amendment 1: • Revised inclusion and exclusion criteria: Removed the requirements of T790M negative results for subjects previously treated with osimertinib; Allowed subjects who had previously received 3rd generation EGFR TKIs other than osimertinib to participate in this study; Excluded subjects with known druggable molecular alterations, known EGFR T790M positive status, and who received live vaccines within 30 days prior to the first dose of study treatment. • Updated the biomarker collection schedule for the randomisation part to add one additional time point (Cycle 1 Day 1) and adjusted the schedule of sample collections to start at Cycle 2 instead of Cycle 4.

    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.
    The study was terminated as Novartis decided to halt enrolment on 11 May 2022. This was a business decision and not related to any safety concerns.
    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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