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   44364   clinical trials with a EudraCT protocol, of which   7388   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 II, Non-comparative, Open label, Multi-centre, International Study of MEDI4736, in Patients with Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum based Chemotherapy Regimen (ATLANTIC)

    Summary
    EudraCT number
    		 2013-005427-16
    Trial protocol
    		 IT   CZ   DE   GB   HU   BE   AT   ES   PL  
    Global end of trial date
    26 Mar 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Oct 2025
    First version publication date
    24 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D4191C00003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02087423
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, United States, MD 20878
    Public contact
    Phillip Dennis, MD, PhD, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Phillip Dennis, MD, PhD, AstraZeneca, ClinicalTrialTransparency@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
    07 Nov 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Jun 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Mar 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of durvalumab (MEDI4736) treatment in terms of Objective Response Rate (ORR) in programmed cell death ligand-1 (PD-L1) positive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Feb 2014
    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
    Italy: 70
    Country: Number of subjects enrolled
    France: 60
    Country: Number of subjects enrolled
    Belgium: 34
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    Germany: 28
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    Poland: 3
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 55
    Country: Number of subjects enrolled
    Japan: 46
    Country: Number of subjects enrolled
    Singapore: 13
    Country: Number of subjects enrolled
    Taiwan: 11
    Country: Number of subjects enrolled
    Philippines: 4
    Country: Number of subjects enrolled
    United States: 49
    Country: Number of subjects enrolled
    Thailand: 4
    Country: Number of subjects enrolled
    Canada: 16
    Worldwide total number of subjects
    444
    EEA total number of subjects
    229
    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)
    265
    From 65 to 84 years
    178
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 First patient in: 25 Feb 2014; Last patient in: 28 Dec 2015. Primary Analysis data cut-off (DCO): 03 Jun 2016; Final Analysis DCO: 7 Nov 2017. Patients were treated with durvalumab (10 milligrams [mg] / kilogram [kg] every 2 weeks [Q2W] intravenously [iv]). 101 sites in 16 countries treated patients in this study.

    Pre-assignment
    Screening details
    		 Patients were enrolled in 3 cohorts. Cohort enrolment was dependent upon epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) status and PD-L1 expression level (percent of tumor cells [TC] with membrane staining).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1 (EGFR/ALK+)
    Arm description
    		 Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received durvalumab 10 mg/kg Q2W iv.

    Arm title
    		 Cohort 2
    Arm description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received durvalumab 10 mg/kg Q2W iv.

    Arm title
    		 Cohort 3 (TC >= 90%)
    Arm description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received durvalumab 10 mg/kg Q2W iv.

    Number of subjects in period 1
    		Cohort 1 (EGFR/ALK+) Cohort 2 Cohort 3 (TC >= 90%)
    Started
    111
    265
    68
    Completed 12 months of treatment
    18
    60
    26
    Completed
    0
    0
    0
    Not completed
    111
    265
    68
         Terminated from study at final DCO
    23
    36
    25
         Consent withdrawn by subject
    20
    20
    3
         Death
    68
    207
    40
         Lost to follow-up
    -
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1 (EGFR/ALK+)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Reporting group title
    Cohort 3 (TC >= 90%)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).

    Reporting group values
    		 Cohort 1 (EGFR/ALK+) Cohort 2 Cohort 3 (TC >= 90%) Total
    Number of subjects
    		 111 265 68 444
    Age Categorical
    age groups of <=18, between 18 and 65, >=65,
    Units: Subjects
        <=18 years
    		 0 0 0 0
        Between 18 and 65 years
    		 66 155 44 265
        >=65 years
    		 45 110 24 179
    Age Continuous
    Units: years
        median (standard deviation)
    		 61.0 ( 11.45 ) 62.0 ( 9.35 ) 61.0 ( 10.58 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 70 103 29 202
        Male
    		 41 162 39 242
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 44 212 42 298
        Black or African American
    		 1 2 2 5
        Asian
    		 66 51 24 141
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 6 19 2 27
        Not Hispanic or Latino
    		 105 246 66 417
    Weight group
    Units: Subjects
        <70 kg
    		 81 146 40 267
        Between 70 and 90 kg
    		 27 97 21 145
        >90 kg
    		 3 22 7 32
    WHO performance status
    Units: Subjects
        (0) Normal activity
    		 45 86 19 150
        (1) Restricted activity
    		 65 178 49 292
        (2) In bed <=50% of the time
    		 1 1 0 2
        (3) In bed >50% of the time
    		 0 0 0 0
        (4) 100% bed ridden
    		 0 0 0 0
    Histology type
    Units: Subjects
        Squamous
    		 1 55 20 76
        Non-squamous
    		 110 210 48 368
    AJCC staging at initial diagnosis
    Per tumor, node, metastasis (TNM) staging system as specified by American Joint Committee on Cancer (AJCC). The staging is determined by a number of different parameters and the higher the staging the worse the prognosis for survival.
    Units: Subjects
        Stage IA
    		 2 3 0 5
        Stage IB
    		 0 4 0 4
        Stage II
    		 0 1 0 1
        Stage IIA
    		 1 1 1 3
        Stage IIB
    		 0 5 0 5
        Stage III
    		 0 1 0 1
        Stage IIIA
    		 9 13 5 27
        Stage IIIB
    		 8 28 9 45
        Stage IV
    		 90 208 53 351
        Missing
    		 1 1 0 2
    Best response to previous therapy
    based on the last therapy received prior to entering the study
    Units: Subjects
        complete response
    		 0 1 0 1
        partial response
    		 31 39 18 88
        stable disease
    		 34 86 18 138
        progression
    		 38 114 26 178
        non-evaluable
    		 2 15 2 19
        not applicable
    		 6 10 4 20
    Time from informed consent to first dose
    Units: Subjects
        <=14 days
    		 21 68 7 96
        Between 14 and 21 days
    		 24 73 13 110
        between 21 and 42 days
    		 65 111 45 221
        > 42 days
    		 1 13 3 17
    Overall disease classification
    either patient has any metastatic site of disease or has only locally advanced sites of disease
    Units: Subjects
        Metastatic
    		 102 245 61 408
        Locally advanced
    		 9 20 7 36
    PD-L1 expression level
    % of tumor cells with membrane staining for PD-L1
    Units: Subjects
        Positive (>=25%)|
    		 77 149 68 294
        Negative (<25%)|
    		 30 95 0 125
        Unknown|
    		 3 21 0 24
        Missing|
    		 1 0 0 1
    Smoking history
    Patients who checked options Cigarettes, Cigarillos, Cigars, Pipe Tobacco, or Tobacco for Smoking are considered smokers.
    Units: Subjects
        Non-smoker
    		 65 39 9 113
        Smoker
    		 46 225 59 330
        Missing
    		 0 1 0 1
    Number of regimens of previous anti-cancer therapy
    Units: Number of regimens
        median (standard deviation)
    		 3 ( 2.00 ) 3 ( 1.38 ) 2 ( 0.80 ) -
    Weight
    Units: kg
        median (standard deviation)
    		 59 ( 14.15 ) 68 ( 14.52 ) 66 ( 15.79 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1 (EGFR/ALK+)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Reporting group title
    Cohort 2
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Reporting group title
    Cohort 3 (TC >= 90%)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).

    Subject analysis set title
    Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%) (FAS - evaluable per ICR)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK mutation positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). Patients with PD-L1 TC>=90% are included in this group. Analysis population: "Full analysis set (FAS) - evaluable for response per Independent Central Review (ICR)" set, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

    Subject analysis set title
    Cohort 1 (EGFR/ALK+) PD-L1- (<25%) (FAS - evaluable per ICR)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK mutation positive and retrospectively or prospectively determined to be PD-L1 low/neg (TC <25%). Analysis population: "FAS – evaluable for response per ICR" set, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

    Subject analysis set title
    Cohort 2 PD-L1+ (>=25%) (FAS - evaluable per ICR)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). Patients with PD-L1 TC>=90% are included in this group. Analysis population: "FAS – evaluable for response per ICR" set, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

    Subject analysis set title
    Cohort 2 PD-L1- (<25%) (FAS - evaluable per ICR)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 low/neg (TC <25%). Analysis population: "FAS – evaluable for response per ICR" set, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

    Subject analysis set title
    Cohort 3 (TC>=90%) (FAS - evaluable per ICR)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC>=90%). Analysis population: "FAS – evaluable for response per ICR" set, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the ICR.

    Subject analysis set title
    Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%) (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK mutation positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). Patients with PD-L1 TC>=90% are included in this group. Analysis population: FAS, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

    Subject analysis set title
    Cohort 1 (EGFR/ALK+) PD-L1- (<25%) (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK mutation positive and retrospectively or prospectively determined to be PD-L1 low/neg (TC <25%). Analysis population: FAS, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

    Subject analysis set title
    Cohort 2 PD-L1+ (>=25%) (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). Patients with PD-L1 TC>=90% are included in this group. Analysis population: FAS, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

    Subject analysis set title
    Cohort 2 PD-L1- (<25%) (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 low/neg (TC <25%). Analysis population: FAS, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

    Subject analysis set title
    Cohort 3 (TC>=90%) (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC>=90%). Analysis population: FAS, which included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

    Primary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    Patients commenced treatment with durvalumab on Day 1 and continued on a Q2W schedule for a maximum of 12 months. Tumor assessments using computed tomography / magnetic resonance imaging were performed every 8 weeks. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) measurements as given by the Independent Central Review (ICR) were used to derive the primary variable of ORR.
    End point type
    Primary
    End point timeframe
    Responses recorded during initial 12 month treatment period (up to primary analysis DCO)
    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 analysis was planned and performed for analysis of the primary end point
    End point values
    		 Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%) (FAS - evaluable per ICR) Cohort 1 (EGFR/ALK+) PD-L1- (<25%) (FAS - evaluable per ICR) Cohort 2 PD-L1+ (>=25%) (FAS - evaluable per ICR) Cohort 2 PD-L1- (<25%) (FAS - evaluable per ICR) Cohort 3 (TC>=90%) (FAS - evaluable per ICR)
    Number of subjects analysed
    74
    28
    146
    93
    68
    Units: % of patients evaluable for response
        number (confidence interval 95%)
    12.2 (5.7 to 21.8)
    3.6 (0.1 to 18.3)
    16.4 (10.8 to 23.5)
    7.5 (3.1 to 14.9)
    30.9 (20.2 to 43.3)
    No statistical analyses for this end point

    Secondary: Time to Response (TTR)

    		 Close Top of page
    End point title
    		 Time to Response (TTR)
    End point description
    TTR (per RECIST 1.1 as assessed by the ICR) is defined as the time from the date of first dose until the date of first documented response (which is subsequently confirmed). TTR was analyzed in patients with objective response in Cohort 2 only.
    End point type
    Secondary
    End point timeframe
    Responses recorded during initial 12 month treatment period (up to primary analysis DCO)
    End point values
    		 Cohort 2 PD-L1+ (>=25%) (FAS - evaluable per ICR) Cohort 2 PD-L1- (<25%) (FAS - evaluable per ICR)
    Number of subjects analysed
    24
    7
    Units: Months
        median (full range (min-max))
    1.9 (1.6 to 16.7)
    2.1 (1.7 to 13.8)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR)

    		 Close Top of page
    End point title
    		 Duration of Response (DoR)
    End point description
    DoR (per RECIST 1.1 as assessed by the ICR) was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring – date of first response + 1). DoR was analyzed in patients with objective response in Cohort 2 only. “99999” in the data table indicates that either the median DoR value and/or the inter-quartile range value was not reached.
    End point type
    Secondary
    End point timeframe
    Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO)
    End point values
    		 Cohort 2 PD-L1+ (>=25%) (FAS - evaluable per ICR) Cohort 2 PD-L1- (<25%) (FAS - evaluable per ICR)
    Number of subjects analysed
    24
    7
    Units: Months
        median (inter-quartile range (Q1-Q3))
    12.3 (7.5 to 99999)
    99999 (7.2 to 99999)
    No statistical analyses for this end point

    Secondary: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Overall survival (OS)
    End point description
    OS was defined as the time from the date of first dose until death due to any cause (ie, date of death or censoring – date of first dose + 1). Results are reported as median OS, calculated using the Kaplan-Meier methodology. “99999” in the data table indicates that the upper limit confidence interval was not reached.
    End point type
    Secondary
    End point timeframe
    From date of first treatment until final DCO (up to approximately 3 years 8 months)
    End point values
    		 Cohort 1 (EGFR/ALK+) PD-L1+ (>=25%) (FAS) Cohort 1 (EGFR/ALK+) PD-L1- (<25%) (FAS) Cohort 2 PD-L1+ (>=25%) (FAS) Cohort 2 PD-L1- (<25%) (FAS) Cohort 3 (TC>=90%) (FAS)
    Number of subjects analysed
    77
    30
    149
    94
    67
    Units: Months
        median (confidence interval 95%)
    13.3 (6.3 to 24.5)
    9.9 (4.2 to 13.3)
    10.9 (8.6 to 13.6)
    9.3 (5.9 to 10.8)
    13.2 (5.9 to 99999)
    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) observed up until 90 days following discontinuation of durvalumab or until the initiation of the first subsequent anticancer therapy following discontinuation of durvalumab (whichever occurred first).
    Adverse event reporting additional description
    All-Cause Mortality is reported for the overall study period, up to the final DCO. Serious and Other (non-serious) TEAE data is reported for the initial treatment phase (maximum of 12 months of treatment).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Cohort 1 (EGFR/ALK+)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK positive and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Reporting group title
    Cohort 3 (TC >=90%)
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and prospectively determined to be PD-L1 high (TC >=90%).

    Reporting group title
    Cohort 2
    Reporting group description
    		 Consisted of patients who were EGFR/ALK wild type/unknown and retrospectively or prospectively determined to be PD-L1 high (TC >=25%). In addition, the cohort included patients enrolled prior to Amendment 1 who were retrospectively determined to be PD-L1 low/neg (TC <25%) or PD-L1 status unknown.

    Serious adverse events
    		 Cohort 1 (EGFR/ALK+) Cohort 3 (TC >=90%) Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 111 (16.22%)
    24 / 68 (35.29%)
    77 / 265 (29.06%)
         number of deaths (all causes)
    70
    41
    217
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    2 / 111 (1.80%)
    0 / 68 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Vascular disorders
    Vena cava thrombosis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Asthenia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Malaise
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Pyrexia
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 68 (2.94%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 111 (0.90%)
    2 / 68 (2.94%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 111 (2.70%)
    0 / 68 (0.00%)
    7 / 265 (2.64%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Pneumonitis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    4 / 265 (1.51%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 68 (1.47%)
    5 / 265 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urine output decreased
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Transaminases increased
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 68 (1.47%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemolytic anaemia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 68 (2.94%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         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 haemorrhage
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Subileus
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Diarrhoea
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal rupture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Pancreatitis acute
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Jaundice cholestatic
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic atrophy
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Bile duct stone
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureteric obstruction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Endocrine disorders
    Hypopituitarism
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Adrenal insufficiency
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes insipidus
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Hypothyroidism
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    8 / 265 (3.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Sepsis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Lung infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central nervous system infection
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    0 / 265 (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
    Cellulitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Diverticulitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal abscess
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 68 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    0 / 265 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1 (EGFR/ALK+) Cohort 3 (TC >=90%) Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    96 / 111 (86.49%)
    60 / 68 (88.24%)
    233 / 265 (87.92%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 111 (4.50%)
    5 / 68 (7.35%)
    11 / 265 (4.15%)
         occurrences all number
    5
    5
    13
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 111 (2.70%)
    5 / 68 (7.35%)
    12 / 265 (4.53%)
         occurrences all number
    3
    5
    14
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 111 (1.80%)
    2 / 68 (2.94%)
    14 / 265 (5.28%)
         occurrences all number
    2
    2
    14
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    4 / 111 (3.60%)
    0 / 68 (0.00%)
    15 / 265 (5.66%)
         occurrences all number
    4
    0
    15
    Weight decreased
         subjects affected / exposed
    3 / 111 (2.70%)
    13 / 68 (19.12%)
    22 / 265 (8.30%)
         occurrences all number
    3
    13
    22
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 111 (5.41%)
    4 / 68 (5.88%)
    12 / 265 (4.53%)
         occurrences all number
    6
    6
    18
    Headache
         subjects affected / exposed
    13 / 111 (11.71%)
    6 / 68 (8.82%)
    26 / 265 (9.81%)
         occurrences all number
    15
    6
    32
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 111 (2.70%)
    8 / 68 (11.76%)
    43 / 265 (16.23%)
         occurrences all number
    3
    8
    52
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    14 / 111 (12.61%)
    4 / 68 (5.88%)
    53 / 265 (20.00%)
         occurrences all number
    15
    4
    76
    Fatigue
         subjects affected / exposed
    15 / 111 (13.51%)
    20 / 68 (29.41%)
    69 / 265 (26.04%)
         occurrences all number
    16
    31
    80
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 111 (2.70%)
    4 / 68 (5.88%)
    10 / 265 (3.77%)
         occurrences all number
    4
    5
    15
    Oedema peripheral
         subjects affected / exposed
    7 / 111 (6.31%)
    9 / 68 (13.24%)
    25 / 265 (9.43%)
         occurrences all number
    8
    13
    25
    Pain
         subjects affected / exposed
    1 / 111 (0.90%)
    4 / 68 (5.88%)
    8 / 265 (3.02%)
         occurrences all number
    1
    4
    8
    Pyrexia
         subjects affected / exposed
    12 / 111 (10.81%)
    12 / 68 (17.65%)
    53 / 265 (20.00%)
         occurrences all number
    14
    16
    81
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    7 / 111 (6.31%)
    1 / 68 (1.47%)
    12 / 265 (4.53%)
         occurrences all number
    8
    1
    12
    Constipation
         subjects affected / exposed
    14 / 111 (12.61%)
    16 / 68 (23.53%)
    37 / 265 (13.96%)
         occurrences all number
    15
    19
    45
    Diarrhoea
         subjects affected / exposed
    11 / 111 (9.91%)
    9 / 68 (13.24%)
    39 / 265 (14.72%)
         occurrences all number
    14
    10
    53
    Nausea
         subjects affected / exposed
    14 / 111 (12.61%)
    12 / 68 (17.65%)
    46 / 265 (17.36%)
         occurrences all number
    16
    15
    57
    Vomiting
         subjects affected / exposed
    13 / 111 (11.71%)
    10 / 68 (14.71%)
    27 / 265 (10.19%)
         occurrences all number
    15
    13
    36
    Abdominal pain
         subjects affected / exposed
    5 / 111 (4.50%)
    4 / 68 (5.88%)
    10 / 265 (3.77%)
         occurrences all number
    6
    6
    10
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    26 / 111 (23.42%)
    13 / 68 (19.12%)
    56 / 265 (21.13%)
         occurrences all number
    32
    16
    67
    Dysphonia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 68 (1.47%)
    14 / 265 (5.28%)
         occurrences all number
    0
    1
    15
    Dyspnoea
         subjects affected / exposed
    13 / 111 (11.71%)
    7 / 68 (10.29%)
    43 / 265 (16.23%)
         occurrences all number
    14
    10
    46
    Haemoptysis
         subjects affected / exposed
    3 / 111 (2.70%)
    4 / 68 (5.88%)
    14 / 265 (5.28%)
         occurrences all number
    3
    6
    20
    Productive cough
         subjects affected / exposed
    4 / 111 (3.60%)
    4 / 68 (5.88%)
    20 / 265 (7.55%)
         occurrences all number
    4
    4
    23
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    7 / 111 (6.31%)
    8 / 68 (11.76%)
    19 / 265 (7.17%)
         occurrences all number
    9
    8
    20
    Pruritus
         subjects affected / exposed
    9 / 111 (8.11%)
    13 / 68 (19.12%)
    27 / 265 (10.19%)
         occurrences all number
    11
    14
    39
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 111 (1.80%)
    2 / 68 (2.94%)
    16 / 265 (6.04%)
         occurrences all number
    2
    2
    16
    Insomnia
         subjects affected / exposed
    10 / 111 (9.01%)
    5 / 68 (7.35%)
    16 / 265 (6.04%)
         occurrences all number
    12
    5
    19
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    11 / 111 (9.91%)
    7 / 68 (10.29%)
    17 / 265 (6.42%)
         occurrences all number
    12
    8
    18
    Hypothyroidism
         subjects affected / exposed
    11 / 111 (9.91%)
    8 / 68 (11.76%)
    19 / 265 (7.17%)
         occurrences all number
    14
    9
    24
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 111 (6.31%)
    5 / 68 (7.35%)
    21 / 265 (7.92%)
         occurrences all number
    7
    6
    25
    Back pain
         subjects affected / exposed
    11 / 111 (9.91%)
    8 / 68 (11.76%)
    23 / 265 (8.68%)
         occurrences all number
    11
    10
    24
    Musculoskeletal pain
         subjects affected / exposed
    4 / 111 (3.60%)
    3 / 68 (4.41%)
    16 / 265 (6.04%)
         occurrences all number
    4
    4
    21
    Neck pain
         subjects affected / exposed
    3 / 111 (2.70%)
    7 / 68 (10.29%)
    8 / 265 (3.02%)
         occurrences all number
    3
    7
    8
    Pain in extremity
         subjects affected / exposed
    5 / 111 (4.50%)
    2 / 68 (2.94%)
    18 / 265 (6.79%)
         occurrences all number
    5
    2
    21
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 111 (1.80%)
    4 / 68 (5.88%)
    4 / 265 (1.51%)
         occurrences all number
    2
    5
    4
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 111 (5.41%)
    6 / 68 (8.82%)
    8 / 265 (3.02%)
         occurrences all number
    9
    6
    8
    Urinary tract infection
         subjects affected / exposed
    4 / 111 (3.60%)
    3 / 68 (4.41%)
    15 / 265 (5.66%)
         occurrences all number
    4
    4
    19
    Viral upper respiratory tract infection
         subjects affected / exposed
    5 / 111 (4.50%)
    11 / 68 (16.18%)
    12 / 265 (4.53%)
         occurrences all number
    6
    18
    13
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    15 / 111 (13.51%)
    12 / 68 (17.65%)
    71 / 265 (26.79%)
         occurrences all number
    15
    12
    77
    Hyponatraemia
         subjects affected / exposed
    2 / 111 (1.80%)
    4 / 68 (5.88%)
    14 / 265 (5.28%)
         occurrences all number
    2
    5
    20

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 May 2014
    • To increase the number of patients (and also the number of sites) expected to undergo a pre-screening assessment in order to recruit the required number of patients fulfilling the new selection criterion of a PD-L1 high tumor. • To remove patient reported outcomes as variables in the study.
    28 Nov 2014
    • Study design was changed to include a third cohort of patients with PD-L1 TC ≥90%. • Extension of recruitment period due to addition of a third patient cohort. The new Cohort 3 (TC ≥90%) was not to start enrolling patients until Cohort 2 was fully enrolled. • Addition of the exploratory analysis of ORR, OS, and Progression Free Survival in patients with PD-L1 low/neg tumors.
    10 Apr 2015
    • To define the primary objective by cohort. • To add key secondary objectives by cohort on the evaluation of the clinical benefit of durvalumab in non-squamous PD-L1 high patients and non-squamous PD-L1 unselected patients. To add other secondary objectives to include the PD-L1 low/neg patients, non-squamous PD-L1 low/neg patients, and PD-L1 unselected patients. To add a footnote to define when objective tumor response should be confirmed because ORR is now included in the secondary objectives section for certain patient populations. • To amend the exploratory objective describing the assessment of efficacy in PD-L1 low/neg patients in Cohort 1 (EGFR/ALK+). • To remove the endpoint of “deep sustained response.” • To add time to response as an endpoint.
    19 Nov 2015
    • To add a secondary objective to assess efficacy in a combined population of Cohorts 2 and 3 who were PD-L1 (TC ≥90%) and to modify the subgroups in Cohort 2 for the secondary efficacy objectives. • To define specific eligibility criteria for patients who were treated through progression or who achieved disease control and restarted treatment upon evidence of progression of disease. • To update the description of the statistical analyses based on the changes to the objectives and to clarify the timing of the final analysis of OS. • To add amylase and lipase laboratory assessments and to revise the frequency of collections for circulating soluble factors and miRNA/mRNA (ie, microRNA/messenger RNA) assessments.
    11 Aug 2017
    • To clarify the timing of scans following the final OS DCO, to reflect the revised duration of re-treatment and to clarify re-treatment eligibility. • To clarify end-of-study procedures for patients who continue in follow-up or re-treatment following the final OS DCO. • To update toxicity management guidelines. • To clarify the conduct of scans and other assessments for patients continuing treatment or re starting durvalumab treatment following the final OS DCO, and to clarify the revised duration of re-treatment. • To clarify that Interactive Voice/Web Response Systems will not be available following final OS DCO. • To clarify IP accountability, safety monitoring and reporting, data collection and patient assessments following final OS DCO. • To clarify that patients in survival follow-up will be withdrawn at the time of final OS DCO. • To provide guidance for Investigators. • To clarify the circumstances under which the study will end.
    10 Jan 2018
    • To update toxicity management guidelines. • To amend section regarding adverse events of special interest to align with updated safety information as found in the current durvalumab Investigator’s Brochure.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Wed Oct 29 08:09:46 CET 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA