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   44365   clinical trials with a EudraCT protocol, of which   7389   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, Randomised, Double-blind, Placebo-controlled, Multicentre Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent (Inoperable Locally Advanced or Metastatic) Triple-negative Breast Cancer

    Summary
    EudraCT number
    		 2016-005119-42
    Trial protocol
    		 HU   GB   ES   FR   FI   PL   PT   IT  
    Global end of trial date
    23 Oct 2024

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MO39193
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03371017
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4058
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    23 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study is to evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in participants with inoperable locally advanced or metastatic triple-negative breast cancer (TNBC).
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Jan 2018
    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: 2
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 4
    Country: Number of subjects enrolled
    Brazil: 36
    Country: Number of subjects enrolled
    Chile: 4
    Country: Number of subjects enrolled
    China: 70
    Country: Number of subjects enrolled
    Cuba: 3
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Spain: 43
    Country: Number of subjects enrolled
    Finland: 8
    Country: Number of subjects enrolled
    France: 57
    Country: Number of subjects enrolled
    United Kingdom: 34
    Country: Number of subjects enrolled
    Hungary: 9
    Country: Number of subjects enrolled
    Italy: 70
    Country: Number of subjects enrolled
    Kazakhstan: 7
    Country: Number of subjects enrolled
    Korea, Republic of: 54
    Country: Number of subjects enrolled
    Morocco: 9
    Country: Number of subjects enrolled
    Mexico: 34
    Country: Number of subjects enrolled
    Montenegro: 1
    Country: Number of subjects enrolled
    Panama: 2
    Country: Number of subjects enrolled
    Peru: 2
    Country: Number of subjects enrolled
    Poland: 8
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Russian Federation: 27
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    Serbia: 19
    Country: Number of subjects enrolled
    Türkiye: 55
    Country: Number of subjects enrolled
    United States: 9
    Country: Number of subjects enrolled
    South Africa: 8
    Worldwide total number of subjects
    595
    EEA total number of subjects
    211
    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)
    535
    From 65 to 84 years
    60
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 595 participants with inoperable locally advanced or metastatic TNBC took part in the study at 126 investigative sites in 28 countries from 11 January 2018 to 23 October 2024.

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1 ratio to receive atezolizumab with chemotherapy or placebo with chemotherapy.

    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, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo + Chemotherapy
    Arm description
    		 Participants received atezolizumab matching placebo, by intravenous (IV) infusion on Day 1 of each cycle along with either gemcitabine, 1000 milligrams per square meter (mg/m^2), followed by carboplatin target under the curve (AUC) 2 milligrams per milliliter per minute (mg/ml/min), both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine 1000 mg/m^2 , twice daily (BID), orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks). Treatment was continued until disease progression (PD), unacceptable toxicity, death or participant or investigator decision to discontinue treatment.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received carboplatin target AUC 2 mg/ml/min, administered by IV infusion on Days 1 and 8 of each cycle, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received capecitabine 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received gemcitabine, 1000 mg/m^2, administered by IV infusion on Days 1 and 8 of each cycle, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Arm title
    		 Atezolizumab + Chemotherapy
    Arm description
    		 Participants received atezolizumab, 1200 milligrams (mg), by IV infusion on Day 1 of each cycle along with either gemcitabine, 1000 mg/m^2, followed by carboplatin target AUC 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine, 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle = 3 weeks). Treatment was continued until PD, unacceptable toxicity, death or participant or investigator decision to discontinue treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267
    Other name
    MPDL3280A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received atezolizumab 1200 mg, by IV infusion on Day 1 of each cycle (1 Cycle = 3 weeks)

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received gemcitabine, 1000 mg/m^2, administered by IV infusion on Days 1 and 8 of each cycle, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received capecitabine 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received carboplatin target AUC 2 mg/ml/min, administered by IV infusion on Days 1 and 8 of each cycle, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks).

    Number of subjects in period 1
    		Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Started
    298
    297
    Safety-evaluable Population
    294
    293
    PD-L1-positive Population
    177
    177
    mITT Population
    192
    188
    Completed
    0
    0
    Not completed
    298
    297
         Consent withdrawn by subject
    20
    25
         Physician decision
    -
    1
         Study Ended by Sponsor
    37
    38
         Protocol Deviation
    -
    1
         Death
    228
    215
         Lost to follow-up
    13
    16
         Reason not Specified
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab matching placebo, by intravenous (IV) infusion on Day 1 of each cycle along with either gemcitabine, 1000 milligrams per square meter (mg/m^2), followed by carboplatin target under the curve (AUC) 2 milligrams per milliliter per minute (mg/ml/min), both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine 1000 mg/m^2 , twice daily (BID), orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks). Treatment was continued until disease progression (PD), unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Reporting group title
    Atezolizumab + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab, 1200 milligrams (mg), by IV infusion on Day 1 of each cycle along with either gemcitabine, 1000 mg/m^2, followed by carboplatin target AUC 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine, 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle = 3 weeks). Treatment was continued until PD, unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Reporting group values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy Total
    Number of subjects
    		 298 297 595
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.4 ( 11.7 ) 48.6 ( 10.9 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 298 297 595
        Male
    		 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 3 5 8
        Asian
    		 66 69 135
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 10 9 19
        White
    		 199 184 383
        More than one race
    		 0 2 2
        Unknown or Not Reported
    		 20 28 48
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 59 51 110
        Not Hispanic or Latino
    		 222 218 440
        Unknown or Not Reported
    		 17 28 45

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab matching placebo, by intravenous (IV) infusion on Day 1 of each cycle along with either gemcitabine, 1000 milligrams per square meter (mg/m^2), followed by carboplatin target under the curve (AUC) 2 milligrams per milliliter per minute (mg/ml/min), both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine 1000 mg/m^2 , twice daily (BID), orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks). Treatment was continued until disease progression (PD), unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Reporting group title
    Atezolizumab + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab, 1200 milligrams (mg), by IV infusion on Day 1 of each cycle along with either gemcitabine, 1000 mg/m^2, followed by carboplatin target AUC 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine, 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle = 3 weeks). Treatment was continued until PD, unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Primary: Overall Survival (OS) in Programmed Death Ligand 1 (PD-L1)-positive Population

    		 Close Top of page
    End point title
    		 Overall Survival (OS) in Programmed Death Ligand 1 (PD-L1)-positive Population
    End point description
    OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day. PD-L1 positive population included all participants randomized in the study whose PD-L1 status was tumor-infiltrating immune cells (IC) of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received.
    End point type
    Primary
    End point timeframe
    Time from randomization to death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    177
    177
    Units: months
        median (confidence interval 95%)
    11.24 (9.00 to 13.31)
    12.09 (10.12 to 15.08)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5891
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.2

    Primary: OS in Modified Intent-to-treat (mITT) Population

    		 Close Top of page
    End point title
    		 OS in Modified Intent-to-treat (mITT) Population
    End point description
    OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received.
    End point type
    Primary
    End point timeframe
    Time from randomization to death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    192
    188
    Units: months
        median (confidence interval 95%)
    9.79 (8.44 to 11.96)
    10.35 (8.90 to 12.88)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6139
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.18

    Secondary: 12-month Survival Rate in PD-L1-positive Population

    		 Close Top of page
    End point title
    		 12-month Survival Rate in PD-L1-positive Population
    End point description
    12-month survival rate was defined as the percentage of participants alive 12 months after randomization. The 12-month survival rates were estimated by Kaplan-Meier methodology. PD-L1 positive population included all participants randomized in the study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Percentages have been rounded off to the nearest whole number.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    177
    177
    Units: percentage of participants
        number (confidence interval 95%)
    47.58 (39.92 to 55.23)
    50.26 (42.61 to 57.91)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6264
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    2.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.14
         upper limit
    		 13.51

    Secondary: 12-month Survival Rate in mITT Population

    		 Close Top of page
    End point title
    		 12-month Survival Rate in mITT Population
    End point description
    12-month survival rate was defined as the percentage of participants alive 12 months after randomization. The 12-month survival rates were estimated by Kaplan-Meier methodology. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Percentages have been rounded off to the nearest whole number.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    192
    188
    Units: percentage of participants
        number (confidence interval 95%)
    42.44 (35.23 to 49.66)
    46.20 (38.84 to 53.56)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.475
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    3.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.55
         upper limit
    		 14.07

    Secondary: 18-month Survival Rate in PD-L1-positive Population

    		 Close Top of page
    End point title
    		 18-month Survival Rate in PD-L1-positive Population
    End point description
    18-month survival rate was defined as the percentage of participants alive 18 months after randomization. The 18-month survival rates were estimated by Kaplan-Meier methodology. PD-L1 positive population included all participants randomized in the study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Percentages have been rounded off to the nearest whole number.
    End point type
    Secondary
    End point timeframe
    18 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    177
    177
    Units: percentage of participants
        number (confidence interval 95%)
    32.48 (25.07 to 39.89)
    33.63 (26.05 to 41.21)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8315
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.45
         upper limit
    		 11.75

    Secondary: 18-month Survival Rate in mITT Population

    		 Close Top of page
    End point title
    		 18-month Survival Rate in mITT Population
    End point description
    18-month survival rate was defined as the percentage of participants alive 18 months after randomization. The 18-month survival rates were estimated by Kaplan-Meier methodology. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Percentages have been rounded off to the nearest whole number.
    End point type
    Secondary
    End point timeframe
    18 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    192
    188
    Units: percentage of participants
        number (confidence interval 95%)
    25.68 (19.15 to 32.21)
    27.05 (20.39 to 33.71)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7738
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.96
         upper limit
    		 10.69

    Secondary: Progression-Free Survival (PFS) in PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS) in PD-L1-positive Population
    End point description
    PFS time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first. PD = as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 millimeters (mm). Data for participants not experiencing PD/death were censored at the last tumour assessment date. If no tumor assessment was performed after randomisation, data were censored at date of randomisation +1 day. PD-L1 positive population = all participants randomized in the study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not assigned study treatment was received.
    End point type
    Secondary
    End point timeframe
    Time from randomization to the first occurrence of PD or death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    177
    177
    Units: months
        median (confidence interval 95%)
    3.58 (3.35 to 4.17)
    4.21 (3.71 to 5.62)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1387
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.06

    Secondary: PFS in mITT Population

    		 Close Top of page
    End point title
    		 PFS in mITT Population
    End point description
    PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Data for participants not experiencing PD or death were censored at the last tumour assessment date. If no tumor assessment was performed after randomisation, data were censored at the date of randomisation +1 day. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received.
    End point type
    Secondary
    End point timeframe
    Time from randomization to the first occurrence of PD or death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    192
    188
    Units: months
        median (confidence interval 95%)
    3.58 (3.06 to 3.81)
    3.71 (2.83 to 4.01)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7317
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.19

    Secondary: Objective Response Rate (ORR) in Response-evaluable Population, Subset of PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) in Response-evaluable Population, Subset of PD-L1-positive Population
    End point description
    ORR was defined as percentage of participants with measurable disease at baseline who achieved a documented unconfirmed objective response (OR). OR = either a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 millimeters (mm). PR = at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD, in the absence of CR. PD-L1 positive population included all participants randomized in the study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Response-evaluable population included participants randomized in the study with measurable disease at baseline. Percentages have been rounded off to nearest whole number.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    159
    154
    Units: percentage of participants
        number (confidence interval 95%)
    28.3 (21.45 to 35.98)
    39.6 (31.83 to 47.80)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0337
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in ORR
    Point estimate
    11.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 22.37

    Secondary: ORR in Response-evaluable Population, Subset of mITT Population

    		 Close Top of page
    End point title
    		 ORR in Response-evaluable Population, Subset of mITT Population
    End point description
    ORR was defined as percentage of participants with measurable disease at baseline who achieved a documented unconfirmed OR. OR was defined as either a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Response-evaluable Population included participants randomized in the study with measurable disease at baseline. Percentages have been rounded off to nearest whole number.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    168
    171
    Units: percentage of participants
        number (confidence interval 95%)
    32.1 (25.16 to 39.77)
    31.0 (24.16 to 38.51)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9755
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in ORR
    Point estimate
    -1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.63
         upper limit
    		 9.34

    Secondary: Duration of Objective Response (DoR) in DoR-evaluable Population Subset of PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Duration of Objective Response (DoR) in DoR-evaluable Population Subset of PD-L1-positive Population
    End point description
    DoR=time from first occurrence of a documented unconfirmed response (CR/PR) until the date of PD per investigator using RECIST v1.1 or death from any cause, whichever occurs first. CR=disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR= ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. PD= ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate absolute increase of ≥5 mm. Appearance of one or more new lesions was also considered progression. PD-L1 positive population=all participants randomized in study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at time of randomization, grouped as per assigned arm, whether assigned treatment was received. DOR-evaluable population=participants randomized in study with measurable disease at baseline & OR.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    45
    61
    Units: months
        median (confidence interval 95%)
    4.14 (3.45 to 5.78)
    6.60 (4.63 to 8.02)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1359
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.11

    Secondary: DoR in DoR-evaluable Population Subset of mITT Population

    		 Close Top of page
    End point title
    		 DoR in DoR-evaluable Population Subset of mITT Population
    End point description
    DoR= time from first occurrence of a documented unconfirmed response (CR/PR) until date of PD per investigator using RECIST v1.1 or death from any cause, whichever occurs first. CR=disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR= ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. PD= ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate absolute increase of ≥5 mm. Appearance of one or more new lesions was considered progression. mITT population=all participants randomized under protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive & PD-L1(SP142)-negative), grouped as per assigned arm, whether assigned treatment was received. DOR-evaluable population=participants randomized in study with measurable disease at baseline & OR.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    54
    53
    Units: months
        median (confidence interval 95%)
    5.22 (3.81 to 6.60)
    5.70 (4.17 to 7.92)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8225
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.43

    Secondary: Clinical Benefit Rate (CBR) in Response-evaluable Population Subset of PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Clinical Benefit Rate (CBR) in Response-evaluable Population Subset of PD-L1-positive Population
    End point description
    CBR=percentage of participants with either an unconfirmed CR/PR /stable disease (SD) that lasts at least 6 months per investigator according to RECIST v1.1. CR=disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. SD=neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD= ≥20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. PD-L1 positive population=all participants randomized in study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Response-evaluable population.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    159
    154
    Units: percentage of participants
        number (confidence interval 95%)
    34.6 (27.23 to 42.53)
    42.9 (34.92 to 51.07)
    No statistical analyses for this end point

    Secondary: CBR in Response-evaluable Population Subset of mITT Population

    		 Close Top of page
    End point title
    		 CBR in Response-evaluable Population Subset of mITT Population
    End point description
    CBR=percentage of participants with either an unconfirmed CR/PR/SD that lasts at least 6 months per investigator according to RECIST v1.1. CR=disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. SD=neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD= ≥20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. mITT population=all participants randomized under protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive & PD-L1(SP142)-negative participants, grouped according to their assigned arm, whether or not the assigned study treatment was received. Response-evaluable population.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    168
    171
    Units: percentage of participants
        number (confidence interval 95%)
    36.3 (29.04 to 44.07)
    35.1 (27.96 to 42.74)
    No statistical analyses for this end point

    Secondary: Confirmed Objective Response Rate (C-ORR) in Response-evaluable Population Subset of PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Confirmed Objective Response Rate (C-ORR) in Response-evaluable Population Subset of PD-L1-positive Population
    End point description
    C-ORR was defined as percentage of participants with measurable disease at baseline who achieved a documented confirmed OR. OR was defined as either a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. PD-L1 positive population included all participants randomized in the study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at the time of randomization, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Response-evaluable population included participants randomized in the study with measurable disease at baseline. Percentages have been rounded off to nearest whole number.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    159
    154
    Units: percentage of participants
        number (confidence interval 95%)
    19.5 (13.65 to 26.52)
    31.2 (23.96 to 39.12)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0172
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in ORR
    Point estimate
    11.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.47
         upper limit
    		 21.87

    Secondary: C-ORR in Response-evaluable Population Subset of mITT Population

    		 Close Top of page
    End point title
    		 C-ORR in Response-evaluable Population Subset of mITT Population
    End point description
    C-ORR was defined as percentage of participants with measurable disease at baseline who achieved a documented confirmed OR. OR was defined as either a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. mITT population included all participants randomized under the protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive and PD-L1(SP142)-negative participants), grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. Response-evaluable population included participants randomized in the study with measurable disease at baseline. Percentages have been rounded off to nearest whole number.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    168
    171
    Units: percentage of participants
        number (confidence interval 95%)
    23.2 (17.06 to 30.34)
    23.4 (17.27 to 30.46)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8679
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in ORR
    Point estimate
    0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.41
         upper limit
    		 9.77

    Secondary: DoR for Confirmed Responders (C-DoR) in C-DoR-evaluable Population Subset of PD-L1-positive Population

    		 Close Top of page
    End point title
    		 DoR for Confirmed Responders (C-DoR) in C-DoR-evaluable Population Subset of PD-L1-positive Population
    End point description
    C-DoR = time from the first occurrence of a documented confirmed response (CR /PR) until date of PD per investigator from tumor assessments using RECIST v1.1 or death from any cause, whichever occurs first. CR = disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR = ≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in absence of CR. PD = ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression. PD-L1 population = all participants randomized in study whose PD-L1 status was tumor-infiltrating IC of 1% or greater (IC1/2/3) at time of randomization, grouped according to their assigned treatment arm, whether assigned study treatment was received. C-DOR-evaluable population.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    31
    48
    Units: months
        median (confidence interval 95%)
    5.78 (4.21 to 8.48)
    7.92 (6.60 to 12.78)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2846
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.26

    Secondary: C-DoR in C-DoR-evaluable Population Subset of mITT Population

    		 Close Top of page
    End point title
    		 C-DoR in C-DoR-evaluable Population Subset of mITT Population
    End point description
    C-DoR = time from first occurrence of a documented confirmed response (CR/PR) until date of PD per investigator from tumor assessments using RECIST v1.1 or death from any cause, whichever occurs first. CR = disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR = ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. PD = ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression. mITT population = all participants randomized under protocol versions prior to version 4.0 (referred to as all-comers, i.e., PD-L1(SP142)-positive & PD-L1(SP142)-negative participants, grouped per assigned treatment arm, whether assigned study treatment was received. C-DOR-evaluable population.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    39
    40
    Units: months
        median (confidence interval 95%)
    6.51 (4.83 to 8.48)
    7.43 (5.55 to 12.98)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9853
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.61

    Secondary: Time to Confirmed Deterioration (TTD) in Global Health Status/Quality of Life (GHS/QoL) According to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30) in PD-L1-positive Population

    		 Close Top of page
    End point title
    		 Time to Confirmed Deterioration (TTD) in Global Health Status/Quality of Life (GHS/QoL) According to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30) in PD-L1-positive Population
    End point description
    TTD in GHS/QoL=minimally important decrease of ≥10 points at 2 consecutive assessment time-points on GHS/QoL scale (Items 29, 30) of EORTC QLQ-C30, consisting of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting & pain), GHS & QoL & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties) with a recall period of the previous week. Participant responses to questions regarding GHS (Question 29: "How would you rate your overall health during the past week?") & QoL (Question 30: "How would you rate your overall quality of life during the past week?") were assessed & were scored on a 7-point scale (1=Very poor; 7=Excellent). Scores are linearly transformed on a scale of 0-100. High score indicating better QoL. PD-L1 positive population. 999=upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    177
    177
    Units: months
        median (confidence interval 95%)
    6.77 (4.30 to 32.69)
    9.43 (6.01 to 999)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4117
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.21

    Secondary: TTD in GHS/QoL According to EORTC QLQ-C30 in mITT Population

    		 Close Top of page
    End point title
    		 TTD in GHS/QoL According to EORTC QLQ-C30 in mITT Population
    End point description
    TTD in GHS/QoL, minimally important decrease of ≥10 points at 2 consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of EORTC QLQ-C30, consisting of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting & pain), GHS & QoL & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties) with a recall period of the previous week. Participant responses to questions (Q) on GHS (Q29: "How would you rate your overall health during the past week?") & QoL (Q30: "How would you rate your overall quality of life during the past week?") were assessed & were scored on a 7-point scale (1=Very poor; 7=Excellent). Scores were linearly transformed on 0-100 scale. High score= better QoL. mITT population=all participants randomized under protocol versions prior to v4.0 (all-comers, i.e., PD-L1(SP142)-positive & PD-L1(SP142)-negative participants.
    End point type
    Secondary
    End point timeframe
    Up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    192
    188
    Units: months
        median (confidence interval 95%)
    7.66 (4.34 to 32.69)
    8.90 (5.88 to 16.82)
    Statistical analysis title
    		 Placebo+Chemotherapy vs Atezolizumab+Chemotherapy
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Placebo + Chemotherapy v Atezolizumab + Chemotherapy
    Number of subjects included in analysis
    380
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7215
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.3

    Secondary: Number of Participants With Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events (AEs)
    End point description
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions that worsen during a study are also considered AEs. Safety-evaluable population included participants who received any amount of any study drug (atezolizumab/placebo or chemotherapy).
    End point type
    Secondary
    End point timeframe
    From treatment initiation up to 90 days after last dose (up to 71 months)
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    294
    293
    Units: participants
    283
    281
    No statistical analyses for this end point

    Secondary: Serum Concentration of Atezolizumab

    		 Close Top of page
    End point title
    		 Serum Concentration of Atezolizumab [1]
    End point description
    Pharmacokinetic (PK)-evaluable population included participants who received any dose of study medication and who had at least one evaluable post-baseline PK sample. n= number of participants with data available for analyses at the specified timepoints. 9999= Geometric mean & geometric coefficient of variation were not estimable as samples were below the limit of quantification.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 1 of Cycles 1, 2, 3 and 4; Post-dose on Day 1 of Cycles 1 and 3 and Treatment Discontinuation Visit (up to 69 months) (1 Cycle= 3 weeks)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Serum concentration was assessed for atezolizumab only.
    End point values
    		 Atezolizumab + Chemotherapy
    Number of subjects analysed
    268
    Units: micrograms/millilitre (µg/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Predose (n=268)
    9999 ( 9999 )
        Cycle 1 Day 1 Post-dose (n=263)
    442 ( 59.7 )
        Cycle 2 Day 1 Pre-dose (n=262)
    87.2 ( 72.7 )
        Cycle 3 Day 1 Predose (n=223)
    140 ( 42.9 )
        Cycle 3 Day 1 Postdose (n=205)
    517 ( 47.7 )
        Cycle 4 Day 1 Predose (n=167)
    157 ( 104.9 )
        Treatment Discontinuation (n=187)
    120 ( 189.7 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

    		 Close Top of page
    End point title
    		 Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [2]
    End point description
    Number of ADA-positive participants after drug administration was determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. The sum of participants who were ADA-positive at postbaseline visits of Cycles 1 to 4 and treatment discontinuation has been reported here. Safety-evaluable population included participants who received any amount of any study drug (atezolizumab/placebo or chemotherapy). Number analyzed included participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycles 1 to 4 and Treatment Discontinuation visit (up to 69 months)
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: ADA 's were assessed for atezolizumab only.
    End point values
    		 Atezolizumab + Chemotherapy
    Number of subjects analysed
    275
    Units: participants
    20
    No statistical analyses for this end point

    Secondary: Number of Participants With PD-L1 Protein Expression in Screening Tumour Tissue and Post-baseline Assessment

    		 Close Top of page
    End point title
    		 Number of Participants With PD-L1 Protein Expression in Screening Tumour Tissue and Post-baseline Assessment
    End point description
    FAS population included all participants randomized in the study, grouped according to their assigned treatment arm, whether or not the assigned study treatment was received. n = number of participants with data available for analyses at the specified category. 9999 = No participants were analyzed for the category.
    End point type
    Secondary
    End point timeframe
    Baseline up to 68 months
    End point values
    		 Placebo + Chemotherapy Atezolizumab + Chemotherapy
    Number of subjects analysed
    298
    297
    Units: participants
        Baseline IC0- Post-baseline IC0 (n=298,297)
    3
    0
        Baseline IC1/2/3- Post-baseline IC0 (n=298,297)
    0
    0
        Baseline IC0- Post-baseline IC1/2/3 (n=298,297)
    0
    0
        BaselineIC1/2/3- Post-baselineIC1/2/3 (n=298,297)
    6
    2
    No statistical analyses for this end point

    Other pre-specified: OS in China Population

    		 Close Top of page
    End point title
    		 OS in China Population [3]
    End point description
    OS was defined as time from randomization to death from any cause. As pre-specfied in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Time from randomization to death (Up to 68 months)
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [4]
    Units: percentage of participants
        median (confidence interval 95%)
    ( to )
    Notes
    [4] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: 12-month Survival Rate in China Population

    		 Close Top of page
    End point title
    		 12-month Survival Rate in China Population [5]
    End point description
    12-month survival rate was defined as the percentage of participants alive 12 months after randomization. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    12 months
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [6]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [6] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: ORR in China Population

    		 Close Top of page
    End point title
    		 ORR in China Population [7]
    End point description
    ORR= percentage of participants with measurable disease at baseline who achieved a documented unconfirmed OR. OR= either a CR or PR, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to end of study (Up to 68 months)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [8]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [8] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: PFS in China Population

    		 Close Top of page
    End point title
    		 PFS in China Population [9]
    End point description
    PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST 1.1, or death from any cause, whichever occurs first. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Time from randomization to the first occurrence of PD or death (Up to 68 months)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [10]
    Units: months
        median (confidence interval 95%)
    ( to )
    Notes
    [10] - No separate China analysis was done.
    No statistical analyses for this end point

    Other pre-specified: 18-month Survival Rate in China Population

    		 Close Top of page
    End point title
    		 18-month Survival Rate in China Population [11]
    End point description
    18-month survival rate was defined as the percentage of participants alive 18 months after randomization. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    18 months
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [12]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [12] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: DoR in China Population

    		 Close Top of page
    End point title
    		 DoR in China Population [13]
    End point description
    DoR=time from first occurrence of a documented unconfirmed OR (CR/PR) until date of PD per the investigator from tumor assessments using RECIST v1.1 or death from any cause, whichever occurs first. CR=disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= ≥30% decrease in the SOD of target lesions, taking as reference baseline SOD, in absence of CR. PD= ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one/more new lesions was also considered progression. As pre-specified in SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [14]
    Units: months
        median (confidence interval 95%)
    ( to )
    Notes
    [14] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: C-DoR in China Population

    		 Close Top of page
    End point title
    		 C-DoR in China Population [15]
    End point description
    C-DoR=time from first occurrence of a documented confirmed response (CR/PR) until date of PD per the investigator from tumor assessments using RECIST v1.1 or death from any cause, whichever occurs first. CR=disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= ≥30% decrease in the SOD of target lesions, taking as reference baseline SOD, in absence of CR. PD= ≥20% increase in SOD of target lesions, taking as reference smallest sum on study, including baseline, in addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one/more new lesions was also considered progression. As pre-specified in SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [16]
    Units: months
        median (confidence interval 95%)
    ( to )
    Notes
    [16] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: C-ORR in China Population

    		 Close Top of page
    End point title
    		 C-ORR in China Population [17]
    End point description
    C-ORR was defined as percentage of participants with measurable disease at baseline who achieved a documented confirmed OR. OR was defined as either a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Up to 68 months
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [18]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [18] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: CBR in China Population

    		 Close Top of page
    End point title
    		 CBR in China Population [19]
    End point description
    CBR= percentage of participants with either an unconfirmed CR/PR/SD that lasts at least 6 months as per investigator according to RECIST v1.1. CR= disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to <10 mm. PR= ≥30% decrease in SOD of target lesions, taking as reference baseline SOD, in absence of CR. SD= neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD= ≥20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. As pre-specified in the SAP, analysis for China population was to be conducted based on data maturity and estimated treatment effect from the global population. As the results for the global population did not meet pre-specified criteria, a separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Up to 68 months
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [20]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [20] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Other pre-specified: TTD in GHS/QoL According to EORTC QLQ-C30 in China Population

    		 Close Top of page
    End point title
    		 TTD in GHS/QoL According to EORTC QLQ-C30 in China Population [21]
    End point description
    TTD in GHS/QoL= minimally important decrease of ≥10 points at 2 consecutive assessment time-points on GHS/QoL scale (Items 29, 30) of EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive, & social), 3 symptom scales (fatigue, nausea & vomiting, &pain),GHS &QoL, & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, & financial difficulties) with a recall period of the previous week. Participant responses to questions regarding GHS (Question 29: "How would you rate your overall health during the past week?") & QoL (Question 30: "How would you rate your overall quality of life during the past week?") were assessed & were scored on a 7-point scale (1=Very poor;7=Excellent). Scores were transformed on scale of 0-100. High score= better QoL. As results for global population did not meet pre-specified criteria, separate analysis for China subpopulation was not conducted.
    End point type
    Other pre-specified
    End point timeframe
    Up to 68 months
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting data for China population only.
    End point values
    		 Placebo + Chemotherapy
    Number of subjects analysed
    0 [22]
    Units: months
        median (confidence interval 95%)
    ( to )
    Notes
    [22] - No separate analysis was performed for the China population.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From treatment initiation up to 90 days after last dose (up to 71 months)
    Adverse event reporting additional description
    Safety-evaluable population included participants who received any amount of any study drug (atezolizumab/placebo or chemotherapy).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Atezolizumab + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab 1200 mg, by IV infusion on Day 1 of each cycle along with either gemcitabine, 1000 mg/m^2, followed by carboplatin target AUC 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine, 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle = 3 weeks). Treatment was continued until PD, unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Reporting group title
    Placebo + Chemotherapy
    Reporting group description
    		 Participants received atezolizumab matching placebo, by IV infusion on Day 1 of each cycle along with either gemcitabine, 1000 mg/m^2, followed by carboplatin target AUC 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each cycle or capecitabine, 1000 mg/m^2, BID, orally on Days 1 to 14, followed by a 7-day rest period in each cycle (1 Cycle= 3 weeks). Treatment was continued until PD, unacceptable toxicity, death or participant or investigator decision to discontinue treatment.

    Serious adverse events
    		 Atezolizumab + Chemotherapy Placebo + Chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    69 / 293 (23.55%)
    57 / 294 (19.39%)
         number of deaths (all causes)
    226
    233
         number of deaths resulting from adverse events
    5
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected neoplasm
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Thrombophlebitis
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 293 (1.02%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 293 (0.68%)
    3 / 294 (1.02%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pleural effusion
         subjects affected / exposed
    4 / 293 (1.37%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 293 (1.02%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pulmonary embolism
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device Extrusion
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    7 / 293 (2.39%)
    7 / 294 (2.38%)
         occurrences causally related to treatment / all
    11 / 11
    9 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 293 (0.68%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 293 (0.68%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Vascular access site pain
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation necrosis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Diabetic hyperglycaemic coma
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         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
    3 / 293 (1.02%)
    4 / 294 (1.36%)
         occurrences causally related to treatment / all
    2 / 3
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood disorder
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    6 / 293 (2.05%)
    8 / 294 (2.72%)
         occurrences causally related to treatment / all
    6 / 6
    10 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 293 (0.00%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    3 / 293 (1.02%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 293 (0.34%)
    3 / 294 (1.02%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         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
    2 / 293 (0.68%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 293 (0.34%)
    3 / 294 (1.02%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cytolysis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    4 / 293 (1.37%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cellulitis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acinetobacter bacteraemia
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 293 (0.00%)
    3 / 294 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 293 (0.68%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 293 (0.34%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 293 (1.37%)
    2 / 294 (0.68%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastitis bacterial
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastitis
         subjects affected / exposed
    1 / 293 (0.34%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 293 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Atezolizumab + Chemotherapy Placebo + Chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    276 / 293 (94.20%)
    278 / 294 (94.56%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    95 / 293 (32.42%)
    100 / 294 (34.01%)
         occurrences all number
    160
    187
    White blood cell count decreased
         subjects affected / exposed
    58 / 293 (19.80%)
    64 / 294 (21.77%)
         occurrences all number
    227
    178
    Platelet count decreased
         subjects affected / exposed
    69 / 293 (23.55%)
    69 / 294 (23.47%)
         occurrences all number
    169
    171
    Neutrophil count decreased
         subjects affected / exposed
    77 / 293 (26.28%)
    88 / 294 (29.93%)
         occurrences all number
    311
    249
    Lymphocyte count decreased
         subjects affected / exposed
    23 / 293 (7.85%)
    36 / 294 (12.24%)
         occurrences all number
    44
    60
    Blood alkaline phosphatase increased
         subjects affected / exposed
    19 / 293 (6.48%)
    19 / 294 (6.46%)
         occurrences all number
    22
    26
    Aspartate aminotransferase increased
         subjects affected / exposed
    86 / 293 (29.35%)
    91 / 294 (30.95%)
         occurrences all number
    138
    195
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    23 / 293 (7.85%)
    17 / 294 (5.78%)
         occurrences all number
    25
    18
    Headache
         subjects affected / exposed
    52 / 293 (17.75%)
    54 / 294 (18.37%)
         occurrences all number
    70
    73
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    26 / 293 (8.87%)
    17 / 294 (5.78%)
         occurrences all number
    40
    34
    Leukopenia
         subjects affected / exposed
    52 / 293 (17.75%)
    42 / 294 (14.29%)
         occurrences all number
    153
    130
    Anaemia
         subjects affected / exposed
    133 / 293 (45.39%)
    138 / 294 (46.94%)
         occurrences all number
    199
    210
    Neutropenia
         subjects affected / exposed
    108 / 293 (36.86%)
    119 / 294 (40.48%)
         occurrences all number
    341
    322
    Thrombocytopenia
         subjects affected / exposed
    52 / 293 (17.75%)
    54 / 294 (18.37%)
         occurrences all number
    117
    123
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    49 / 293 (16.72%)
    39 / 294 (13.27%)
         occurrences all number
    68
    61
    Oedema peripheral
         subjects affected / exposed
    17 / 293 (5.80%)
    13 / 294 (4.42%)
         occurrences all number
    22
    14
    Mucosal inflammation
         subjects affected / exposed
    16 / 293 (5.46%)
    14 / 294 (4.76%)
         occurrences all number
    18
    19
    Fatigue
         subjects affected / exposed
    69 / 293 (23.55%)
    62 / 294 (21.09%)
         occurrences all number
    85
    75
    Asthenia
         subjects affected / exposed
    66 / 293 (22.53%)
    73 / 294 (24.83%)
         occurrences all number
    95
    93
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    17 / 293 (5.80%)
    19 / 294 (6.46%)
         occurrences all number
    19
    24
    Abdominal pain
         subjects affected / exposed
    14 / 293 (4.78%)
    18 / 294 (6.12%)
         occurrences all number
    16
    23
    Vomiting
         subjects affected / exposed
    67 / 293 (22.87%)
    69 / 294 (23.47%)
         occurrences all number
    109
    90
    Nausea
         subjects affected / exposed
    121 / 293 (41.30%)
    122 / 294 (41.50%)
         occurrences all number
    236
    179
    Dyspepsia
         subjects affected / exposed
    8 / 293 (2.73%)
    16 / 294 (5.44%)
         occurrences all number
    8
    19
    Diarrhoea
         subjects affected / exposed
    46 / 293 (15.70%)
    40 / 294 (13.61%)
         occurrences all number
    75
    55
    Constipation
         subjects affected / exposed
    61 / 293 (20.82%)
    61 / 294 (20.75%)
         occurrences all number
    87
    77
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    19 / 293 (6.48%)
    23 / 294 (7.82%)
         occurrences all number
    21
    25
    Cough
         subjects affected / exposed
    38 / 293 (12.97%)
    39 / 294 (13.27%)
         occurrences all number
    44
    43
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    33 / 293 (11.26%)
    22 / 294 (7.48%)
         occurrences all number
    49
    25
    Pruritus
         subjects affected / exposed
    24 / 293 (8.19%)
    15 / 294 (5.10%)
         occurrences all number
    35
    15
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    32 / 293 (10.92%)
    29 / 294 (9.86%)
         occurrences all number
    40
    34
    Alopecia
         subjects affected / exposed
    21 / 293 (7.17%)
    29 / 294 (9.86%)
         occurrences all number
    22
    30
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    25 / 293 (8.53%)
    19 / 294 (6.46%)
         occurrences all number
    26
    21
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    25 / 293 (8.53%)
    12 / 294 (4.08%)
         occurrences all number
    29
    13
    Hyperthyroidism
         subjects affected / exposed
    15 / 293 (5.12%)
    0 / 294 (0.00%)
         occurrences all number
    17
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    28 / 293 (9.56%)
    30 / 294 (10.20%)
         occurrences all number
    30
    35
    Bone pain
         subjects affected / exposed
    10 / 293 (3.41%)
    16 / 294 (5.44%)
         occurrences all number
    11
    22
    Myalgia
         subjects affected / exposed
    19 / 293 (6.48%)
    19 / 294 (6.46%)
         occurrences all number
    25
    20
    Pain in extremity
         subjects affected / exposed
    24 / 293 (8.19%)
    27 / 294 (9.18%)
         occurrences all number
    26
    30
    Arthralgia
         subjects affected / exposed
    40 / 293 (13.65%)
    29 / 294 (9.86%)
         occurrences all number
    46
    35
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    18 / 293 (6.14%)
    13 / 294 (4.42%)
         occurrences all number
    26
    20
    Urinary tract infection
         subjects affected / exposed
    16 / 293 (5.46%)
    9 / 294 (3.06%)
         occurrences all number
    22
    9
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    50 / 293 (17.06%)
    32 / 294 (10.88%)
         occurrences all number
    51
    33

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Nov 2017
    Protocol v2: • Two exclusion criteria were added -Symptomatic or rapid visceral progression -No prior treatment with an anthracycline and taxane • Updates were made to the list of events requiring permanent discontinuation of atezolizumab/placebo (addition of any recurrent Grade 2 or 3 hypophysitis or Grade 4 hypophysitis) • A new appendix was added to the protocol, detailing the risks associated with atezolizumab, and providing guidelines for the management of AEs associated with atezolizumab.
    18 Feb 2019
    Protocol v3: • Inclusion criteria were updated • Safety updates were included based on the atezolizumab Investigator’s Brochure (Version 14, dated October 2018) • Additional explanation was provided to clarify the conditions and process for unblinding in case of disease progression. • To correct a previous inconsistency within the protocol, references to measurements of capecitabine concentrations were removed. • Clarification was provided for cases where only one component of the study treatment (i.e., atezolizumab/placebo or chemotherapy) was discontinued permanently. In these cases, treatment with the other drugs may continue as long as the participants experienced clinical benefit. • Provisions had been included to allow the administration of carboplatin in exceptional cases of absolute neutrophil counts (ANC) being between >1500 and 1500 x 106 /L and platelet count ≥100,000 x 106 /L shows no evidence of fever or infection. • It was clarified that assessments on Day 8 of each cycle only applied to participants receiving carboplatin/gemcitabine, and that the coagulation panel tests on Day 1 of each cycle only applied to participants receiving capecitabine.
    26 Aug 2019
    Protocol v4: • Analysis of the primary endpoint was modified to occur hierarchically in the following fixed order: 1. OS in the PD-L1-positive population, 2. OS in the modified ITT population. • The primary analysis of OS to be completed when the required number of 247 mortality events have occurred in the PD-L1-positive subpopulation. • PFS and ORR were retained as secondary endpoints and were tested hierarchically after OS, in the PD-L1-positive population first, followed by the modified ITT population. • Two new secondary endpoints were added to the protocol: C-ORR and C-DoR. • To allow for the primary analysis of OS completed in the PD-L1-positive population, recruitment was to be extended as follows: after approximately 350 participants with inoperable recurrent TNBC had been randomised in the study, approximately 190 additional participants with PD-L1-positive tumour status were to be randomised. • The estimated total sample size was increased from 350 to 540 randomised participants. • The total study recruitment period was extended from 23 to 48 months. • It was anticipated that the final analysis of OS in the PD-L1-positive population would occur approximately 58 months (compared to the previously estimated 35 months in the modified ITT population) after FPI. • The analysis populations were updated as follows: -The PD-L1-positive subpopulation included all participants randomised in study whose tumour shows PD-L1 expression of ≥1%at the time of randomisation. -The modified ITT population included all participants randomised in study before protocol version 4.0. -Sensitivity analyses of OS were to be completed on the FAS population, defined as all participants randomised in the study (before and after protocol amendment 4.0). -Supplemental analyses of OS were to be conducted to assess the consistency of treatment effect in the PD-L1-positive population randomised before and after protocol version 4.0.
    26 Feb 2020
    Protocol v5: • New section was added to evaluate whether the efficacy of atezolizumab plus chemotherapy compared with placebo plus chemotherapy as measured by OS and other efficacy endpoints in the China population was consistent with the efficacy observed in the Global population. • Recruitment of all-comers was closed after 382 all-comers were randomised in the Global study (compared to the planned approximately 350 participants); of these, 140 (36.6%) had PD-L1-positive tumour status (compared to the previously estimated 40%). To enable the primary analysis of OS in 330 PD-L1- positive participants, approximately 190 additional participants with PD-L1-positive tumour status were to be randomised, for a total of 572 randomised participants in the Global study (compared to the previously planned 540 participants). • Additional participants with PD-L1-positive tumour status were subsequently randomised in to 1:1 ratio in China only, for a total enrolment of approximately 70 participants with PD-L1-positive tumour status in mainland China, referred to as the China population. • For participants randomised in China, the clinical cut-off (CCO) date for the final OS analysis was) when the target number of mortality events had occurred in the PD-L1-positive population. • Inclusion criterion #7 was updated to indicate that Chinese traditional medicines with an approved indication for cancer treatment were permitted as long as the last administration occurred at least 2 weeks prior to randomisation. • It was clarified that if additional enrolment in China was initiated, a separate analysis would be performed for the China population. • The final analysis of OS in the China population would be conducted when sufficient OS events had occurred. • The efficacy analyses would be unstratified for China Population instead of stratified.
    21 Dec 2020
    Protocol v6: • The list of approved indications for atezolizumab was updated to include unresectable or metastatic hepatocellular carcinoma and BRAF V600 mutation-positive unresectable or metastatic melanoma. • An updated summary of treatment-emergent (treatment-induced plus treatment-enhanced) anti-drug antibodies (ADAs) for Atezolizumab was included. • The anticipated length of recruitment was revised from 48 to 53 months. • The minimum survival follow-up has was updated from 10 to 5 months. • The requirement for the Sponsor and its agents, the investigator and research staff to remain blinded to PD-L1 status is no longer applicable, has been deleted. • It was clarified that completion of Patient-Reported Outcomes (PROs) after laboratory tests was permitted, provided there was no prior discussion of the participant’s laboratory results or health record with clinic staff, and that the PROs were completed before drug administration. • The description of the EORTC QLQ-C30 scales and scoring was updated for better clarity. • General completion times were added for each PRO measure.
    13 Jan 2021
    Protocol v7: • The list of approved indications for atezolizumab was updated to include unresectable or metastatic hepatocellular carcinoma and BRAF V600 mutation-positive unresectable or metastatic melanoma. • Key updates include the insertion of the results for the: -Final overall survival (OS) analysis for Study WO29522 (IMpassion 130) -Primary analysis of progression-free survival (PFS) for Study MO39196 (IMpassion131)
    12 Nov 2021
    Protocol v8: • The list of approved indications for atezolizumab was updated. • The requirement for additional samples for ADA analyses from patients experiencing immune-mediated adverse events was removed • Clarification was added to indicate that herbal therapies not intended for the treatment of cancer may be used during the study at the discretion of the investigator. • Clarification was added that screening bone or PET scan must be performed to evaluate for bone metastases • Language regarding PFS events in participants with missing data will be relocated to the SAP
    25 Jan 2023
    Protocol v9: • Details on the timing of analysis of China population was provided to align with Statistical Analysis Plan (SAP) • The indication-specific companion diagnostics approval status of the VENTANA PD-L1 (SP142) Assay for the assessment of the PD-L1 protein was updated • Due to potentially still ongoing enrolment of participants in China at the time of primary endpoint analysis, clarification was added to indicate that treatment unblinding at the study level at the time of primary endpoint analysis only applied to randomized participants. Unblinding at the study level did not apply to participants who were not randomized at the time of primary endpoint analysis • PRO evaluable population was removed, as PRO analysis was done using PD-L1 (SP142) positive population and the mITT population

    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-Mon Dec 08 08:08:09 CET 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA