Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44234   clinical trials with a EudraCT protocol, of which   7336   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Study to Determine the Efficacy of Adjuvant Durvalumab in Combination with Platinum-based Chemotherapy in Completely Resected Stage II-III NSCLC (MERMAID-1)

    Summary
    EudraCT number
    		 2020-000556-35
    Trial protocol
    		 GB   NL   DK   BG   HU   DE   BE   SE   PL   CZ   GR   IT   FR   RO  
    Global end of trial date
    31 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Sep 2024
    First version publication date
    08 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D910LC00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04385368
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Forskargatan 18, Södertälje, Sweden, 151 85
    Public contact
    Global Clinical Lead, AstraZeneca AB, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca AB, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Aug 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of durvalumab + standard of care (SoC) chemotherapy compared to placebo + SoC chemotherapy as measured by disease-free survival (DFS) in all participants.
    Protection of trial subjects
    This study was conducted in accordance with the protocol and with the following: consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonization Good Clinical Practice Guidelines, and applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Jul 2020
    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
    Argentina: 1
    Country: Number of subjects enrolled
    United States: 6
    Country: Number of subjects enrolled
    Viet Nam: 1
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Greece: 5
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Türkiye: 4
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    Australia: 2
    Country: Number of subjects enrolled
    Brazil: 3
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    India: 3
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Japan: 14
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Country: Number of subjects enrolled
    Russian Federation: 5
    Country: Number of subjects enrolled
    Thailand: 2
    Worldwide total number of subjects
    89
    EEA total number of subjects
    36
    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)
    43
    From 65 to 84 years
    46
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This Phase III, multicenter, randomized, double-blind, placebo-controlled study was conducted in participants with completely resected stage II to III non-small cell lung cancer (NSCLC) at 63 sites across 25 countries from 17 July 2020 to 31 August 2023.

    Pre-assignment
    Screening details
    		 A total of 89 participants were randomized in a 1:1 ratio to durvalumab given concurrently with SoC chemotherapy followed by durvalumab monotherapy, or to a matched placebo given concurrently with SoC chemotherapy followed by placebo.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Durvalumab + SoC
    Arm description
    		 Participants received durvalumab 1500 milligrams (mg) via intravenous (IV) infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (area under the serum drug concentration-time curve [AUC] 6) and paclitaxel 200 milligram per square meter (mg/m^2) via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    MEDI4736
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab was provided as 500-mg vial solution for infusion after dilution, 50 milligrams per milliliter (mg/mL). Participants received durvalumab 1500 mg via IV infusion over 60 minutes on Day 1 of each 3-week cycle for 14 cycles, unless protocol-specified discontinuation criterion was met.

    Investigational medicinal product name
    Pemetrexed + Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed (500 mg/m^2) and carboplatin (AUC 5) on Day 1 of each 3-week cycle for 4 cycles.

    Investigational medicinal product name
    Pemetrexed + Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed (500 mg/m^2) and cisplatin (75 mg/m^2) on Day 1 of each 3-week cycle for 4 cycles.

    Investigational medicinal product name
    Carboplatin + Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel (200 mg/m^2) and carboplatin (AUC 6) on Day 1 of each 3-week cycle for 4 cycles.

    Arm title
    		 Placebo + SoC
    Arm description
    		 Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Matching placebo was provided as vial solution for infusion after dilution. Participants received matching placebo via IV infusion over 60 minutes on Day 1 of each 3-week cycle for 14 cycles, unless protocol-specified discontinuation criterion was met.

    Investigational medicinal product name
    Carboplatin + Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel (200 mg/m^2) and carboplatin (AUC 6) on Day 1 of each 3-week cycle for 4 cycles.

    Investigational medicinal product name
    Pemetrexed + Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed (500 mg/m^2) and cisplatin (75 mg/m^2) on Day 1 of each 3-week cycle for 4 cycles.

    Investigational medicinal product name
    Pemetrexed + Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed (500 mg/m^2) and carboplatin (AUC 5) on Day 1 of each 3-week cycle for 4 cycles.

    Number of subjects in period 1
    		Durvalumab + SoC Placebo + SoC
    Started
    45
    44
    Completed
    33
    36
    Not completed
    12
    8
         Physician decision
    3
    -
         Consent withdrawn by subject
    4
    3
         Death
    5
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Durvalumab + SoC
    Reporting group description
    		 Participants received durvalumab 1500 milligrams (mg) via intravenous (IV) infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (area under the serum drug concentration-time curve [AUC] 6) and paclitaxel 200 milligram per square meter (mg/m^2) via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Reporting group title
    Placebo + SoC
    Reporting group description
    		 Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Reporting group values
    		 Durvalumab + SoC Placebo + SoC Total
    Number of subjects
    		 45 44 89
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 65.5 ( 8.78 ) 64.5 ( 7.37 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 17 15 32
        Male
    		 28 29 57
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 9 18 27
        White
    		 35 22 57
        Not reported
    		 1 3 4
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 4 1 5
        Not Hispanic or Latino
    		 40 43 83
        Missing
    		 1 0 1
    Subject analysis sets

    Subject analysis set title
    Durvalumab + SoC: MRD+ Analysis Set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received durvalumab 1500 mg via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Subject analysis set title
    Placebo + SoC: MRD+ Analysis Set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Subject analysis sets values
    		 Durvalumab + SoC: MRD+ Analysis Set Placebo + SoC: MRD+ Analysis Set
    Number of subjects
    12
    11
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    69.3 ( 7.41 )
    67.4 ( 6.22 )
    Sex: Female, Male
    Units: participants
        Female
    6
    3
        Male
    6
    8
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    0
    0
        Asian
    2
    4
        White
    10
    7
        Not reported
    0
    0
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    0
    0
        Not Hispanic or Latino
    12
    11
        Missing
    0
    0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Durvalumab + SoC
    Reporting group description
    		 Participants received durvalumab 1500 milligrams (mg) via intravenous (IV) infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (area under the serum drug concentration-time curve [AUC] 6) and paclitaxel 200 milligram per square meter (mg/m^2) via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Reporting group title
    Placebo + SoC
    Reporting group description
    		 Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Subject analysis set title
    Durvalumab + SoC: MRD+ Analysis Set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received durvalumab 1500 mg via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Subject analysis set title
    Placebo + SoC: MRD+ Analysis Set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Primary: Disease-free Survival (DFS) in Full Analysis Set (FAS) (Using Investigator Assessments According to Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1])

    		 Close Top of page
    End point title
    		 Disease-free Survival (DFS) in Full Analysis Set (FAS) (Using Investigator Assessments According to Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1]) [1]
    End point description
    DFS was defined as the time from the date of randomization until either of the following events, whichever occurred first: disease recurrence using Investigator RECIST 1.1 assessments (i.e., local or regional recurrence, distant recurrence, second primary NSCLC) or death from any cause. The FAS included all randomized participants. 9999 indicates that median and upper limit of confidence interval were not estimable due to insufficient number of participants with events at study closure and due to limited duration of follow-up.
    End point type
    Primary
    End point timeframe
    Every 12 weeks (q12w) ± 1 week until appearance of RECIST 1.1-defined disease recurrence or until primary DFS analysis, up to 33.28 months
    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: As the endpoint was descriptive in nature, no statistical analysis was reported.
    End point values
    		 Durvalumab + SoC Placebo + SoC
    Number of subjects analysed
    45
    44
    Units: months
        median (confidence interval 95%)
    9999 (14.062 to 9999)
    9999 (21.914 to 9999)
    No statistical analyses for this end point

    Secondary: DFS in Minimal Residual Disease-positive (MRD+) Analysis Set (Using Investigator Assessments According to RECIST 1.1)

    		 Close Top of page
    End point title
    		 DFS in Minimal Residual Disease-positive (MRD+) Analysis Set (Using Investigator Assessments According to RECIST 1.1)
    End point description
    DFS was defined as the time from the date of randomization until either of the following events, whichever occurred first: disease recurrence using Investigator RECIST 1.1 assessments (i.e., local or regional recurrence, distant recurrence, second primary NSCLC) or death from any cause. The MRD+ analysis set included all participants in the FAS who were MRD+, as determined by results from the post-surgical plasma sample based on the assay that was used at the time of randomization assay. 9999 indicates that median and/or upper limit of confidence interval were not estimable due to insufficient number of participants with events at study closure and due to limited duration of follow-up.
    End point type
    Secondary
    End point timeframe
    Every 12 weeks (q12w) ± 1 week until appearance of RECIST 1.1-defined disease recurrence or until primary DFS analysis, up to 33.28 months
    End point values
    		 Durvalumab + SoC: MRD+ Analysis Set Placebo + SoC: MRD+ Analysis Set
    Number of subjects analysed
    12
    11
    Units: months
        median (confidence interval 95%)
    16.7 (2.661 to 9999)
    9999 (5.585 to 9999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) in FAS

    		 Close Top of page
    End point title
    		 Overall Survival (OS) in FAS
    End point description
    OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The FAS included all randomized participants. 9999 indicates that median, upper and lower limit of confidence interval were not estimable due to insufficient number of participants with events at study closure and due to limited duration of follow-up.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until death due to any cause, up to 35 months
    End point values
    		 Durvalumab + SoC Placebo + SoC
    Number of subjects analysed
    45
    44
    Units: months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: OS in MRD+ Analysis Set

    		 Close Top of page
    End point title
    		 OS in MRD+ Analysis Set
    End point description
    OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The MRD+ analysis set included all participants in the FAS who were MRD+, as determined by results from the post-surgical plasma sample based on the assay that was used at the time of randomization assay. 9999 indicates that median and upper limit of confidence interval were not estimable due to insufficient number of participants with events at study closure and due to limited duration of follow-up.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until death due to any cause, up to 35 months
    End point values
    		 Durvalumab + SoC: MRD+ Analysis Set Placebo + SoC: MRD+ Analysis Set
    Number of subjects analysed
    12
    11
    Units: months
        median (confidence interval 95%)
    9999 (9.331 to 9999)
    9999 (13.372 to 9999)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events(TEAEs) were collected from first dose of study treatment up to 90 days after last dose of study treatment, 19.1 months. All-cause mortality was assessed from start of randomization up to completion of study, 35 months.
    Adverse event reporting additional description
    The safety analysis set consisted of all randomized participants who received at least 1 dose of study treatment (durvalumab/placebo and/or SoC chemotherapy).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo + SoC
    Reporting group description
    		 Participants received matching placebo via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by matching placebo continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Reporting group title
    Durvalumab + SoC
    Reporting group description
    		 Participants received durvalumab 1500 mg via IV infusion in combination with SoC chemotherapy on Day 1 of each 3-week cycle for up to 4 cycles, followed by durvalumab monotherapy continued on Day 1 of each 4-week cycle for up to 10 additional cycles until unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. For participants with tumors of squamous histology, permitted SoC chemotherapy was a combination of carboplatin (AUC 6) and paclitaxel 200 mg/m^2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles. For participants with tumors of non-squamous tumor histology, permitted SoC chemotherapy regimens were pemetrexed 500 mg/m^2 in combination with either cisplatin 75 mg/m^2 or carboplatin AUC 5, all via IV infusion on Day 1 of each 3-week cycle, for 4 cycles.

    Serious adverse events
    		 Placebo + SoC Durvalumab + SoC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 44 (22.73%)
    14 / 45 (31.11%)
         number of deaths (all causes)
    5
    6
         number of deaths resulting from adverse events
    1
    1
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Parkinson's disease
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 45 (4.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 45 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Nausea
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypopituitarism
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 45 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + SoC Durvalumab + SoC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 44 (100.00%)
    43 / 45 (95.56%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 44 (9.09%)
    3 / 45 (6.67%)
         occurrences all number
    4
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    12 / 44 (27.27%)
    15 / 45 (33.33%)
         occurrences all number
    13
    18
    Asthenia
         subjects affected / exposed
    4 / 44 (9.09%)
    7 / 45 (15.56%)
         occurrences all number
    4
    10
    Pyrexia
         subjects affected / exposed
    2 / 44 (4.55%)
    6 / 45 (13.33%)
         occurrences all number
    3
    7
    Oedema peripheral
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    3
    3
    Malaise
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 45 (2.22%)
         occurrences all number
    3
    4
    Respiratory, thoracic and mediastinal disorders
    Hiccups
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 45 (4.44%)
         occurrences all number
    5
    2
    Dyspnoea
         subjects affected / exposed
    4 / 44 (9.09%)
    4 / 45 (8.89%)
         occurrences all number
    4
    5
    Cough
         subjects affected / exposed
    5 / 44 (11.36%)
    7 / 45 (15.56%)
         occurrences all number
    5
    9
    Productive cough
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    3
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 44 (9.09%)
    6 / 45 (13.33%)
         occurrences all number
    4
    7
    Investigations
    Weight decreased
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 45 (4.44%)
         occurrences all number
    3
    2
    Platelet count decreased
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 45 (6.67%)
         occurrences all number
    3
    5
    Neutrophil count decreased
         subjects affected / exposed
    5 / 44 (11.36%)
    8 / 45 (17.78%)
         occurrences all number
    9
    15
    White blood cell count decreased
         subjects affected / exposed
    2 / 44 (4.55%)
    7 / 45 (15.56%)
         occurrences all number
    5
    10
    Nervous system disorders
    Peripheral sensory neuropathy
         subjects affected / exposed
    6 / 44 (13.64%)
    1 / 45 (2.22%)
         occurrences all number
    6
    1
    Paraesthesia
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    4
    4
    Neuropathy peripheral
         subjects affected / exposed
    5 / 44 (11.36%)
    7 / 45 (15.56%)
         occurrences all number
    5
    7
    Headache
         subjects affected / exposed
    4 / 44 (9.09%)
    8 / 45 (17.78%)
         occurrences all number
    6
    9
    Dysgeusia
         subjects affected / exposed
    2 / 44 (4.55%)
    4 / 45 (8.89%)
         occurrences all number
    4
    4
    Dizziness
         subjects affected / exposed
    2 / 44 (4.55%)
    4 / 45 (8.89%)
         occurrences all number
    4
    4
    Anosmia
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    12 / 44 (27.27%)
    15 / 45 (33.33%)
         occurrences all number
    13
    21
    Neutropenia
         subjects affected / exposed
    3 / 44 (6.82%)
    8 / 45 (17.78%)
         occurrences all number
    5
    10
    Thrombocytopenia
         subjects affected / exposed
    1 / 44 (2.27%)
    5 / 45 (11.11%)
         occurrences all number
    1
    6
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    4
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    3 / 44 (6.82%)
    5 / 45 (11.11%)
         occurrences all number
    7
    8
    Stomatitis
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    3
    3
    Nausea
         subjects affected / exposed
    18 / 44 (40.91%)
    19 / 45 (42.22%)
         occurrences all number
    35
    32
    Gastrooesophageal reflux disease
         subjects affected / exposed
    7 / 44 (15.91%)
    1 / 45 (2.22%)
         occurrences all number
    7
    1
    Dry mouth
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 45 (6.67%)
         occurrences all number
    1
    3
    Abdominal pain
         subjects affected / exposed
    2 / 44 (4.55%)
    5 / 45 (11.11%)
         occurrences all number
    2
    8
    Abdominal pain upper
         subjects affected / exposed
    5 / 44 (11.36%)
    0 / 45 (0.00%)
         occurrences all number
    6
    0
    Constipation
         subjects affected / exposed
    17 / 44 (38.64%)
    12 / 45 (26.67%)
         occurrences all number
    24
    15
    Diarrhoea
         subjects affected / exposed
    7 / 44 (15.91%)
    11 / 45 (24.44%)
         occurrences all number
    7
    15
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    9 / 44 (20.45%)
    13 / 45 (28.89%)
         occurrences all number
    10
    13
    Dry skin
         subjects affected / exposed
    3 / 44 (6.82%)
    4 / 45 (8.89%)
         occurrences all number
    3
    4
    Pruritus
         subjects affected / exposed
    6 / 44 (13.64%)
    6 / 45 (13.33%)
         occurrences all number
    8
    8
    Rash
         subjects affected / exposed
    5 / 44 (11.36%)
    8 / 45 (17.78%)
         occurrences all number
    5
    9
    Rash maculo-papular
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    3
    3
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 44 (0.00%)
    6 / 45 (13.33%)
         occurrences all number
    0
    6
    Hypothyroidism
         subjects affected / exposed
    1 / 44 (2.27%)
    6 / 45 (13.33%)
         occurrences all number
    1
    6
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 45 (6.67%)
         occurrences all number
    1
    4
    Back pain
         subjects affected / exposed
    3 / 44 (6.82%)
    5 / 45 (11.11%)
         occurrences all number
    3
    6
    Arthralgia
         subjects affected / exposed
    8 / 44 (18.18%)
    7 / 45 (15.56%)
         occurrences all number
    13
    7
    Pain in extremity
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 45 (4.44%)
         occurrences all number
    5
    3
    Myalgia
         subjects affected / exposed
    5 / 44 (11.36%)
    4 / 45 (8.89%)
         occurrences all number
    12
    4
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 45 (4.44%)
         occurrences all number
    3
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 45 (6.67%)
         occurrences all number
    1
    3
    COVID-19
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    3
    3
    Metabolism and nutrition disorders
    Hypomagnesaemia
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 45 (6.67%)
         occurrences all number
    4
    3
    Decreased appetite
         subjects affected / exposed
    7 / 44 (15.91%)
    9 / 45 (20.00%)
         occurrences all number
    11
    14

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Apr 2021
    Removed secondary objectives and endpoints that were no longer considered necessary to analyze. Removed never smokers from the eligible population to reduce the probability of screen failure due to failure to meet the 50 variants required for MRD assessment. Changes were made to aspects of the screening procedures for simplification and clarification to provide flexibility during screening; and to reflect real world practice.
    06 May 2021
    Updated numbering in sections: Exclusion Criteria and Lifestyle Restrictions. Updated SAS definition. Clarified regarding prohibited prior radiotherapy.
    02 Aug 2022
    Revised planned analyses of objectives and endpoints based on the reduced sample size, following study enrollment closure on 25 May 2022. Removed text for long-term survival follow up. Updated end of study definition to account for early closure of study enrollment.

    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.
    Sponsor closed enrollment early due to changes in treatment landscape. Interpretation of efficacy results is inconclusive due to small sample size, resulting in wide confidence intervals, and limited follow-up. No new safety concerns were identified.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA