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    Clinical Trial Results:
    A Randomized, Multicenter, Phase Ib/III Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous Compared With Atezolizumab Intravenous in Patients With Previously Treated Locally Advanced or Metastatic Non-small Cell Lung Cancer

    Summary
    EudraCT number
    		 2018-002328-18
    Trial protocol
    		 LV   PL   HU   GR   BG   IT  
    Global end of trial date
    22 Nov 2024

    Results information
    Results version number
    		 v2(current)
    This version publication date
    26 Oct 2025
    First version publication date
    12 May 2023
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    BP40657
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03735121
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    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
    22 Nov 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Nov 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of Part 1 of the study was to determine the dose of atezolizumab given as subcutaneous (SC) injection that was predicted to yield drug exposure that is comparable to that of atezolizumab intravenous (IV) infusion. The main purpose of Part 2 of the study was to demonstrate non-inferiority of exposure to atezolizumab SC compared with atezolizumab IV.
    Protection of trial subjects
    All participants were required to sign the informed consent form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Dec 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: 7
    Country: Number of subjects enrolled
    Chile: 50
    Country: Number of subjects enrolled
    Costa Rica: 8
    Country: Number of subjects enrolled
    Guatemala: 7
    Country: Number of subjects enrolled
    New Zealand: 17
    Country: Number of subjects enrolled
    Peru: 18
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Latvia: 13
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    Spain: 37
    Country: Number of subjects enrolled
    Türkiye: 54
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Ukraine: 28
    Country: Number of subjects enrolled
    Brazil: 22
    Country: Number of subjects enrolled
    China: 10
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Russian Federation: 44
    Country: Number of subjects enrolled
    South Africa: 3
    Country: Number of subjects enrolled
    Thailand: 69
    Worldwide total number of subjects
    438
    EEA total number of subjects
    86
    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)
    229
    From 65 to 84 years
    207
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 438 participants with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) who were cancer immunotherapy (CIT)-naïve and for whom prior platinum-based therapy failed took part in the study across 23 countries from 27 December 2018 to 22 November 2024.

    Pre-assignment
    Screening details
    		 The study had 2 parts: Part 1 (Dose Finding) & Part 2 (Dose Confirmation). Participants received atezolizumab (co-mixed with recombinant human hyaluronidase [rHuPH20]) SC & IV in Part 1 & atezolizumab (co-formulated with rHuPH20) SC/IV in Part 2. The study is considered "Completed" as all the pre-planned study activities & analyses were performed.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Open-label study, with allocation for Part 1 being non-randomized, whereas for Part 2 it is randomized.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg
    Arm description
    		 Participants received atezolizumab, 1800 milligrams (mg), co-mixed with rHuPH20, as SC injection on Cycle 1 Day 1 (1 cycle=21 days), followed by atezolizumab, 1200 mg, as an IV infusion, every 3 weeks (Q3W) on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression (PD), loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab, 1200 mg, as an IV infusion, Q3W (1 cycle=21 days).

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F01
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection on Cycle 1 Day 1 (1 cycle=21 days).

    Arm title
    		 Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg
    Arm description
    		 Participants received atezolizumab, 1200 mg, co-mixed with rHuPH20, as SC injection, Q2W, on Day 1 of the first 3 cycles (Cycle 1-3=14 days), followed by atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab, 1200 mg, as an IV infusion, Q3W (1 cycle=21 days).

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F01
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Atezolizumab, 1200 mg, co-mixed with rHuPH20, as SC injection, Q2W, on Day 1 of the first 3 cycles (1 Cycle = 21 days).

    Arm title
    		 Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Arm description
    		 Participants received atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection, Q3W, on Day 1 of first 3 cycles, followed by atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 for subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab, 1200 mg, as an IV infusion, Q3W (1 cycle=21 days).

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F01
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection, Q3W, on Day 1 of first 3 cycles (1 Cycle = 21 days).

    Arm title
    		 Part 2: Atezolizumab IV 1200 mg
    Arm description
    		 Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F03
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of each cycle (1 cycle=21 days).

    Arm title
    		 Part 2: Atezolizumab SC 1875 mg
    Arm description
    		 Participants received atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F01
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days).

    Number of subjects in period 1
    		Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Started
    13
    15
    39
    124
    247
    Completed
    8
    7
    13
    0
    0
    Not completed
    5
    8
    26
    124
    247
         Consent withdrawn by subject
    1
    1
    6
    8
    11
         Study Ended by Sponsor
    1
    -
    1
    17
    28
         Death
    3
    6
    19
    97
    205
         New Therapy
    -
    1
    -
    -
    -
         Lost to follow-up
    -
    -
    -
    2
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 milligrams (mg), co-mixed with rHuPH20, as SC injection on Cycle 1 Day 1 (1 cycle=21 days), followed by atezolizumab, 1200 mg, as an IV infusion, every 3 weeks (Q3W) on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression (PD), loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, co-mixed with rHuPH20, as SC injection, Q2W, on Day 1 of the first 3 cycles (Cycle 1-3=14 days), followed by atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection, Q3W, on Day 1 of first 3 cycles, followed by atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 for subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants received atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Reporting group values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg Total
    Number of subjects
    		 13 15 39 124 247 438
    Age Categorical
    Units: participants
        <=18 years
    		 0 0 0 0 0 0
        Between 18 and 65 years
    		 8 7 19 58 137 229
        >=65 years
    		 5 8 20 66 110 209
    Sex: Female, Male
    Units: participants
        Female
    		 8 6 12 42 72 140
        Male
    		 5 9 27 82 175 298
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 9 15 24
        Asian
    		 2 2 1 33 47 85
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 2 1 3
        Black or African American
    		 0 0 0 1 2 3
        White
    		 8 11 36 74 174 303
        More than one race
    		 0 0 0 5 6 11
        Unknown or Not Reported
    		 3 2 2 0 2 9
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 1 5 12 36 61 115
        Not Hispanic or Latino
    		 9 7 25 88 185 314
        Not Stated
    		 3 3 2 0 0 8
        Unknown
    		 0 0 0 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 milligrams (mg), co-mixed with rHuPH20, as SC injection on Cycle 1 Day 1 (1 cycle=21 days), followed by atezolizumab, 1200 mg, as an IV infusion, every 3 weeks (Q3W) on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression (PD), loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, co-mixed with rHuPH20, as SC injection, Q2W, on Day 1 of the first 3 cycles (Cycle 1-3=14 days), followed by atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection, Q3W, on Day 1 of first 3 cycles, followed by atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 for subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants received atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Subject analysis set title
    Part 2: Atezolizumab IV/Atezolizumab SC
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W, or atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity. HCPs who administered the IV or SC formulations completed the HCP SC versus IV Perspective Questionnaire and the HCP SC Perspective Questionnaire.

    Primary: Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1

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    End point title
    		 Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1 [1] [2]
    End point description
    Pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis for this endpoint.
    [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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    15
    35
    Units: micrograms per milliliter (μg/mL)
        geometric mean (geometric coefficient of variation)
    121 ( 42.8 )
    77.5 ( 51.4 )
    78.3 ( 88.6 )
    No statistical analyses for this end point

    Primary: Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1

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    End point title
    		 Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1 [3]
    End point description
    Per Protocol PK evaluable population included all participants randomized to the atezolizumab SC and atezolizumab IV treatment arms who did not have protocol deviations that could affect Cycle 1 observed Ctrough results.
    End point type
    Primary
    End point timeframe
    Predose on Day 1 of Cycle 2 (Cycle length =21 days)
    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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    97
    205
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    85.4 ( 34.1 )
    89.4 ( 127.1 )
    Statistical analysis title
    		 Analysis of Co-primary Endpoint Ctrough
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    302
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.24
    Notes
    [4] - The null hypothesis that atezolizumab SC is inferior to atezolizumab IV is rejected if the lower bound of the 2-sided 90% confidence interval [CI] of the geometric mean ratio is greater than or equal to (≥) the non-inferiority margin 0.8.

    Primary: Part 2: Area Under the Concentration-Time Curve from Time Zero to 21 Days (AUC 0-21 d) at Cycle 1

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    End point title
    		 Part 2: Area Under the Concentration-Time Curve from Time Zero to 21 Days (AUC 0-21 d) at Cycle 1 [5]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis.
    End point type
    Primary
    End point timeframe
    From start of dosing up to Day 21 in Cycle 1 (Cycle length = 21 days)
    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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: micrograms day per mL (μg*day/mL)
        geometric mean (geometric coefficient of variation)
    3327.9 ( 19.4 )
    2907.1 ( 35.9 )
    Statistical analysis title
    		 Analysis of Co-primary Endpoint AUC
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 0.92
    Notes
    [6] - The null hypothesis that atezolizumab SC is inferior to atezolizumab IV is rejected if the lower bound of the 2-sided 90% CI of the geometric mean ratio is ≥ the non-inferiority margin 0.8.

    Secondary: Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab

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    End point title
    		 Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab [7]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
    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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    14
    30
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    251 ( 40.9 )
    129 ( 42.5 )
    181 ( 38.3 )
    No statistical analyses for this end point

    Secondary: Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab

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    End point title
    		 Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab [8]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
    Notes
    [8] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    14
    30
    Units: days
        median (full range (min-max))
    3.02 (2.93 to 7.80)
    3.45 (3.00 to 8.95)
    3.92 (2.99 to 7.11)
    No statistical analyses for this end point

    Secondary: Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab

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    End point title
    		 Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab [9]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Predose and up to 21 days post dose in Cycle 1 for cohorts 1 and 3 and from predose up to 14 days post last dose in Cycle 1 for cohort 2 (Cycle length= 21 days for cohorts 1 and 3 and 14 days for cohort 2)
    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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    14
    30
    Units: μg*day/mL
        geometric mean (geometric coefficient of variation)
    3870 ( 38.6 )
    1410 ( 41.8 )
    2820 ( 38.6 )
    No statistical analyses for this end point

    Secondary: Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration

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    End point title
    		 Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration [10]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab and had at least 1 evaluable post dose PK sample that could affect PK results. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at a given timepoint. 99999 = no participants were analyzed for this endpoint at the specified timepoint; 9999 = data was not evaluable as all the samples were below lower limit of quantification (BLLQ); 999999 = Since only 1 participant was analyzed the geometric coefficient of variation could not be calculated. Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2. Day=D; Cycle=C.
    End point type
    Secondary
    End point timeframe
    Cohort 1: Predose: D1 & postdose: D1, 3, 8 of C1; Cohort 2: Pre & postdose: D1 of C1, 3 & postdose: D3, 8 of C1, Predose: D1 of C2; Cohort 3: Pre & postdose: D1 of C1, 2 & postdose: D3, 8 of C1, D2, 4 & 9 of C2 & pre dose: D1 of C3
    Notes
    [10] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    15
    39
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1: Pre-dose (n=13,15,39)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Cycle 1 Day 1: Post-dose (n=13,15,39)
    116 ( 57.8 )
    61.7 ( 70.9 )
    108 ( 57.6 )
        Cycle 1 Day 3: Post-dose (n=13,15,38)
    247 ( 40.5 )
    123 ( 44.3 )
    166 ( 45.7 )
        Cycle 1 Day 8: Post-dose (n=13,15,37)
    230 ( 36.6 )
    110 ( 45.0 )
    162 ( 43.5 )
        Cycle 2 Day 1: Pre-dose (n=0,15,35)
    99999 ( 99999 )
    77.5 ( 51.4 )
    78.3 ( 88.6 )
        Cycle 2 Day 1: Post-dose (n=0,0,36)
    99999 ( 99999 )
    99999 ( 99999 )
    87.7 ( 64.7 )
        Cycle 2 Day 2: Post-dose (n=0,0,36)
    99999 ( 99999 )
    99999 ( 99999 )
    183 ( 46.1 )
        Cycle 2 Day 4: Post-dose (n=0,0,34)
    99999 ( 99999 )
    99999 ( 99999 )
    245 ( 42.0 )
        Cycle 2 Day 9: Post-dose (n=0,0,35)
    99999 ( 99999 )
    99999 ( 99999 )
    225 ( 37.2 )
        Cycle 3 Day 1: Pre-dose (n=0,14,33)
    99999 ( 99999 )
    104 ( 47.8 )
    123 ( 57.2 )
        Cycle 3 Day 1: Post-dose (n=0,1,0)
    99999 ( 99999 )
    189 ( 999999 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of Participants with Adverse Events (AEs)

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    End point title
    		 Part 1: Percentage of Participants with Adverse Events (AEs) [11]
    End point description
    An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. 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 which worsen during a study are also considered as AEs. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0). Safety-evaluable population included all participants who received at least one dose of atezolizumab (IV or SC), with participants grouped according to treatment received. Percentages have been rounded to one decimal place.
    End point type
    Secondary
    End point timeframe
    From initiation of study treatment up to approximately 69 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: No statistical analysis for this endpoint.
    End point values
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Number of subjects analysed
    13
    15
    39
    Units: percentage of participants
        number (not applicable)
    100
    86.7
    84.6
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Participants with AEs

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    End point title
    		 Part 2: Percentage of Participants with AEs [12]
    End point description
    An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. 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 which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, V5.0. Safety-evaluable population included all participants who received at least one dose of atezolizumab (IV or SC), with participants grouped according to treatment received. Percentages have been rounded to one decimal place.
    End point type
    Secondary
    End point timeframe
    From initiation of study treatment up to approximately 44.7 months
    Notes
    [12] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    124
    247
    Units: percentage of participants
        number (not applicable)
    85.5
    89.9
    No statistical analyses for this end point

    Secondary: Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1

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    End point title
    		 Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1 [13]
    End point description
    PK evaluable population included all participants randomized to the atezolizumab SC and atezolizumab IV treatment arms with at least one post-baseline PK sample. Number analyzed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (Cycle length=21 days)
    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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    88.7 ( 26.2 )
    97.2 ( 42.3 )
    No statistical analyses for this end point

    Secondary: Part 2: Model Predicted Ctrough at Steady State (Ctrough,ss) of Atezolizumab

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    End point title
    		 Part 2: Model Predicted Ctrough at Steady State (Ctrough,ss) of Atezolizumab [14]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab (atezolizumab SC or atezolizumab IV) and had at least 1 evaluable post dose PK sample. Number analyzed is the number of participants with data available for analysis. 1 cycle=21 days. Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo.
    End point type
    Secondary
    End point timeframe
    Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)
    Notes
    [14] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    179 ( 38.8 )
    205 ( 58.1 )
    No statistical analyses for this end point

    Secondary: Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab

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    End point title
    		 Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab [15]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab (atezolizumab SC or atezolizumab IV) and had at least 1 evaluable post dose PK sample. Number analyzed is the number of participants with data available for analysis. 1 cycle=21 days. Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo
    End point type
    Secondary
    End point timeframe
    Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: ug*day/mL
        geometric mean (geometric coefficient of variation)
    6107 ( 27.3 )
    6163 ( 46.7 )
    No statistical analyses for this end point

    Secondary: Part 2: Objective Response Rate (ORR)

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    End point title
    		 Part 2: Objective Response Rate (ORR) [16]
    End point description
    ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD in the absence of CR. Response-evaluable population included all participants with measurable disease at baseline. Percentage of participants who achieved confirmed objective response (CR or PR) have been reported. Percentages have been rounded to one decimal place.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 months
    Notes
    [16] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    124
    245
    Units: percentage of participants
        number (confidence interval 95%)
    10.5 (5.7 to 17.3)
    11.0 (7.4 to 15.6)
    Statistical analysis title
    		 Atezolizumab IV 1200 mg vs Atezolizumab SC 1875 mg
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    369
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8757
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in ORR
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.56
         upper limit
    		 7.63

    Secondary: Part 2: Progression-free Survival (PFS)

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    End point title
    		 Part 2: Progression-free Survival (PFS) [17]
    End point description
    PFS was defined as the time from study start 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 SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. PFS was analyzed using the Kaplan-Meier method. FAS included all randomized participants, with participants grouped according to their assigned treatment.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    124
    247
    Units: months
        median (confidence interval 95%)
    2.9 (1.8 to 4.2)
    2.8 (2.7 to 4.1)
    Statistical analysis title
    		 Atezolizumab IV 1200 mg vs Atezolizumab SC 1875 mg
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6906
    Method
    		 Logrank
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.33

    Secondary: Part 2: Overall Survival (OS)

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    End point title
    		 Part 2: Overall Survival (OS) [18]
    End point description
    OS was defined as the time from the date of study randomization to the date of death from any cause. FAS included all randomized participants, with participants grouped according to their assigned treatment.
    End point type
    Secondary
    End point timeframe
    Up to approximately 44.7 months
    Notes
    [18] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    124
    247
    Units: months
        median (confidence interval 95%)
    10.1 (7.5 to 12.3)
    10.9 (8.5 to 14.4)
    Statistical analysis title
    		 Atezolizumab IV 1200 mg vs Atezolizumab SC 1875 mg
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9766
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.27

    Secondary: Part 2: Duration of response (DOR)

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    End point title
    		 Part 2: Duration of response (DOR) [19]
    End point description
    DOR was defined as the time from first occurrence of a confirmed objective response (CR or PR) to PD as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. CR was defined as the disappearance of all target lesions and 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 was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SODs must also demonstrate an absolute increase of ≥ 5 mm. DOR-evaluable population included all participants with a measurable disease at baseline and a post-baseline confirmed objective response (CR/PR). 9999 = upper limit of the 95% CI was not estimable due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to approximately 25 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    13
    27
    Units: months
        median (confidence interval 95%)
    11.2 (4.2 to 9999)
    15.1 (5.6 to 9999)
    Statistical analysis title
    		 Atezolizumab IV 1200 mg vs Atezolizumab SC 1875 mg
    Comparison groups
    Part 2: Atezolizumab IV 1200 mg v Part 2: Atezolizumab SC 1875 mg
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8375
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 2.42

    Secondary: Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL) 57 Physical Functioning Score

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    End point title
    		 Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL) 57 Physical Functioning Score [20]
    End point description
    EORTC IL57 questionnaire has 10 items and covers 3 scales: physical functioning (PF), role functioning (RF) and global health status/quality of life (GHS/QoL) and 1 item from EORTC IL. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks and short walks; need to stay in bed or a chair; need help with eating, dressing, bathing or using toilet. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical function scale. For this scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome. FAS. Number analyzed is the number of participants with data available for analysis. n = number analyzed at specified time point. 9999 = No participants were analyzed at specified time point. 99999 = Standard deviation (SD) was not estimable for since only 1 participant was evaluated.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (TDV) (up to approximately 44 months)
    Notes
    [20] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    117
    243
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=117,243)
    74.53 ( 20.37 )
    72.15 ( 21.94 )
        Change at Day 1 Cycle 2 (n=106,219)
    -6.23 ( 19.17 )
    -4.23 ( 17.01 )
        Change at Day 1 Cycle 3 (n=86,183)
    -4.55 ( 19.04 )
    -4.99 ( 17.63 )
        Change at Day 1 Cycle 4 (n=80,167)
    -5.75 ( 22.04 )
    -4.47 ( 20.86 )
        Change at Day 1 Cycle 5 (n=64,134)
    -1.46 ( 21.40 )
    -2.14 ( 20.05 )
        Change at Day 1 Cycle 6 (n=58,120)
    -2.76 ( 25.68 )
    -0.67 ( 20.09 )
        Change at Day 1 Cycle 8 (n=47,95)
    -0.14 ( 19.24 )
    -0.42 ( 19.76 )
        Change at Day 1 Cycle 10 (n=41,81)
    -1.46 ( 22.39 )
    0.82 ( 20.96 )
        Change at Day 1 Cycle 12 (n=35,70)
    0.95 ( 22.64 )
    1.14 ( 20.43 )
        Change at Day 1 Cycle 14 (n=30,60)
    0.67 ( 19.37 )
    1.11 ( 18.82 )
        Change at Day 1 Cycle 16 (n=28,53)
    -2.14 ( 23.38 )
    2.26 ( 19.30 )
        Change at Day 1 Cycle 18 (n=23,50)
    -0.87 ( 19.10 )
    0.67 ( 19.30 )
        Change at Day 1 Cycle 20 (n=21,44)
    -1.59 ( 22.30 )
    -0.15 ( 19.53 )
        Change at Day 1 Cycle 22 (n=18,36)
    -2.22 ( 23.54 )
    -1.67 ( 23.66 )
        Change at Day 1 Cycle 24 (n=16,34)
    -0.83 ( 22.69 )
    -1.76 ( 20.97 )
        Change at Day 1 Cycle 26 (n=16,31)
    0.83 ( 17.36 )
    -1.94 ( 23.61 )
        Change at Day 1 Cycle 28 (n=14,23)
    2.38 ( 14.70 )
    0.51 ( 19.46 )
        Change at Day 1 Cycle 30 (n=13,21)
    2.05 ( 16.42 )
    0.95 ( 18.89 )
        Change at Day 1 Cycle 32 (n=12,22)
    -6.67 ( 21.27 )
    0.61 ( 22.34 )
        Change at Day 1 Cycle 34 (n=11,20)
    -2.42 ( 16.40 )
    3.00 ( 26.62 )
        Change at Day 1 Cycle 36 (n=11,20)
    0.61 ( 17.24 )
    6.00 ( 23.59 )
        Change at Day 1 Cycle 38 (n=11,18)
    3.64 ( 17.22 )
    4.07 ( 24.96 )
        Change at Day 1 Cycle 40 (n=11,18)
    0.00 ( 25.65 )
    1.11 ( 23.79 )
        Change at Day 1 Cycle 42 (n=8,18)
    1.67 ( 19.76 )
    2.96 ( 21.36 )
        Change at Day 1 Cycle 44 (n=8,16)
    5.83 ( 12.57 )
    5.00 ( 21.15 )
        Change at Day 1 Cycle 46 (n=8,17)
    5.83 ( 16.88 )
    5.88 ( 26.34 )
        Change at Day 1 Cycle 48 (n=7,14)
    8.57 ( 10.69 )
    8.10 ( 24.13 )
        Change at Day 1 Cycle 50 (n=7,11)
    4.76 ( 14.76 )
    9.09 ( 29.25 )
        Change at Day 1 Cycle 52 (n=6,10)
    12.22 ( 12.94 )
    5.33 ( 24.30 )
        Change at Day 1 Cycle 54 (n=3,8)
    11.11 ( 10.18 )
    6.67 ( 29.81 )
        Change at Day 1 Cycle 56 (n=2,3)
    10.00 ( 4.71 )
    8.89 ( 13.88 )
        Change at Day 1 Cycle 58 (n=1,2)
    6.67 ( 99999 )
    3.33 ( 14.14 )
        Change at Day 1 Cycle 60 (n=1,1)
    20.00 ( 99999 )
    13.33 ( 99999 )
        Change at Day 1 Cycle 62 (n=1,1)
    13.33 ( 99999 )
    13.33 ( 99999 )
        Change at Day 1 Cycle 64 (n=0,1)
    9999 ( 9999 )
    13.33 ( 99999 )
        Change at TDV (n=74,149)
    -19.01 ( 28.26 )
    -15.68 ( 25.67 )
    No statistical analyses for this end point

    Secondary: Part 2: Change From Baseline in EORTC IL57 Role Functioning Score

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    End point title
    		 Part 2: Change From Baseline in EORTC IL57 Role Functioning Score [21]
    End point description
    EORTC IL57 questionnaire has 10 items and covers 3 scales: PF, RF and GHS/QoL and 1 item from EORTC IL. RF scale has 2 items evaluating extent to which participants are limited in doing work and pursuing leisure activities in the previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for the role functioning scale. For this scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome.  FAS included all randomized participants, with participants grouped according to their assigned treatment. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point. 9999 = No participants were analyzed at the specified time point. 99999 = SD was not estimable for since only 1 participant was evaluated.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    117
    242
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=117,242)
    74.93 ( 25.67 )
    74.86 ( 27.51 )
        Change at Day 1 Cycle 2 (n=106,218)
    0.31 ( 29.46 )
    -4.36 ( 24.48 )
        Change at Day 1 Cycle 3 (n=86,182)
    -3.29 ( 27.51 )
    -4.67 ( 25.83 )
        Change at Day 1 Cycle 4 (n=80,167)
    -0.83 ( 26.90 )
    -6.59 ( 28.63 )
        Change at Day 1 Cycle 5 (n=64,134)
    2.34 ( 31.13 )
    -5.22 ( 30.27 )
        Change at Day 1 Cycle 6 (n=58,119)
    0.00 ( 32.14 )
    -5.74 ( 29.39 )
        Change at Day 1 Cycle 8 (n=47,94)
    4.96 ( 29.47 )
    -1.95 ( 25.50 )
        Change at Day 1 Cycle 10 (n=41,81)
    1.63 ( 29.06 )
    -0.82 ( 24.71 )
        Change at Day 1 Cycle 12 (n=35,69)
    4.29 ( 29.80 )
    -2.66 ( 30.20 )
        Change at Day 1 Cycle 14 (n=30,60)
    6.11 ( 22.09 )
    -3.61 ( 30.24 )
        Change at Day 1 Cycle 16 (n=28,53)
    -0.60 ( 29.91 )
    -1.26 ( 27.12 )
        Change at Day 1 Cycle 18 (n=23,50)
    0.72 ( 21.60 )
    -2.00 ( 27.90 )
        Change at Day 1 Cycle 20 (n=21,44)
    7.94 ( 30.10 )
    -2.65 ( 27.83 )
        Change at Day 1 Cycle 22 (n=18,36)
    6.48 ( 28.66 )
    -5.09 ( 34.23 )
        Change at Day 1 Cycle 24 (n=16,34)
    3.13 ( 24.51 )
    -4.41 ( 29.39 )
        Change at Day 1 Cycle 26 (n=16,31)
    4.17 ( 36.77 )
    0.54 ( 27.38 )
        Change at Day 1 Cycle 28 (n=14,23)
    7.14 ( 16.94 )
    5.07 ( 29.91 )
        Change at Day 1 Cycle 30 (n=13,21)
    -2.56 ( 20.24 )
    3.17 ( 31.01 )
        Change at Day 1 Cycle 32 (n=12,22)
    -6.94 ( 19.41 )
    -0.76 ( 31.49 )
        Change at Day 1 Cycle 34 (n=11,20)
    -6.06 ( 22.70 )
    0.00 ( 34.20 )
        Change at Day 1 Cycle 36 (n=11,20)
    -3.03 ( 17.98 )
    1.67 ( 31.48 )
        Change at Day 1 Cycle 38 (n=11,18)
    4.55 ( 16.82 )
    5.56 ( 26.20 )
        Change at Day 1 Cycle 40 (n=11,18)
    1.52 ( 24.10 )
    1.85 ( 28.52 )
        Change at Day 1 Cycle 42 (n=8,18)
    -6.25 ( 23.46 )
    3.70 ( 32.11 )
        Change at Day 1 Cycle 44 (n=8,16)
    -2.08 ( 16.52 )
    7.29 ( 31.60 )
        Change at Day 1 Cycle 46 (n=8,17)
    0.00 ( 23.57 )
    4.90 ( 32.68 )
        Change at Day 1 Cycle 48 (n=7,14)
    2.38 ( 20.25 )
    8.33 ( 31.86 )
        Change at Day 1 Cycle 50 (n=7,11)
    2.38 ( 20.25 )
    13.64 ( 36.38 )
        Change at Day 1 Cycle 52 (n=6,10)
    2.78 ( 28.71 )
    1.67 ( 24.15 )
        Change at Day 1 Cycle 54 (n=3,8)
    -11.11 ( 34.69 )
    2.08 ( 36.12 )
        Change at Day 1 Cycle 56 (n=2,3)
    0.00 ( 23.57 )
    -5.56 ( 19.25 )
        Change at Day 1 Cycle 58 (n=1,2)
    -33.33 ( 99999 )
    0.00 ( 23.57 )
        Change at Day 1 Cycle 60 (n=1,1)
    16.67 ( 99999 )
    16.67 ( 99999 )
        Change at Day 1 Cycle 62 (n=1,1)
    16.67 ( 99999 )
    16.67 ( 99999 )
        Change at Day 1 Cycle 64 (n=0,1)
    9999 ( 9999 )
    16.67 ( 99999 )
        Change at TDV (n=74,149)
    -20.27 ( 33.70 )
    -21.14 ( 34.80 )
    No statistical analyses for this end point

    Secondary: Part 2: Change From Baseline in EORTC IL57 Global Health Status Score

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    End point title
    		 Part 2: Change From Baseline in EORTC IL57 Global Health Status Score [22]
    End point description
    EORTC IL57 questionnaire has 10 items and covers 3 scales: PF, RF and GHS/QoL and 1 item from EORTC IL. GHS/QoL scale has 2 items evaluating participants' overall health and QoL in previous week. Questions are answered on a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For this scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 = best possible score. Higher score indicates better outcome. FAS included all randomized participants, with participants grouped according to their assigned treatment. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point. 9999 = No participants were analyzed at the specified time point. 99999 = SD was not estimable since only 1 participant was evaluated.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months)
    Notes
    [22] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    117
    242
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=117,242)
    66.52 ( 17.68 )
    63.50 ( 22.00 )
        Change at Day 1 Cycle 2 (n=106,218)
    -3.54 ( 21.33 )
    -2.48 ( 21.77 )
        Change at Day 1 Cycle 3 (n=86,182)
    -2.91 ( 20.92 )
    -1.83 ( 23.04 )
        Change at Day 1 Cycle 4 (n=80,167)
    -2.71 ( 19.61 )
    -2.25 ( 22.21 )
        Change at Day 1 Cycle 5 (n=64,134)
    0.65 ( 19.26 )
    -1.43 ( 25.35 )
        Change at Day 1 Cycle 6 (n=58,119)
    -0.14 ( 21.99 )
    0.14 ( 22.94 )
        Change at Day 1 Cycle 8 (n=47,94)
    3.01 ( 18.26 )
    1.86 ( 22.74 )
        Change at Day 1 Cycle 10 (n=41,81)
    5.28 ( 19.87 )
    0.72 ( 23.17 )
        Change at Day 1 Cycle 12 (n=35,69)
    6.19 ( 18.45 )
    -2.78 ( 18.56 )
        Change at Day 1 Cycle 14 (n=30,60)
    7.50 ( 17.42 )
    1.94 ( 19.67 )
        Change at Day 1 Cycle 16 (n=28,53)
    6.55 ( 17.77 )
    1.73 ( 18.52 )
        Change at Day 1 Cycle 18 (n=23,50)
    4.71 ( 19.11 )
    0.67 ( 17.56 )
        Change at Day 1 Cycle 20 (n=21,44)
    9.52 ( 16.73 )
    -0.95 ( 18.52 )
        Change at Day 1 Cycle 22 (n=18,36)
    5.56 ( 21.20 )
    0.00 ( 19.92 )
        Change at Day 1 Cycle 24 (n=16,34)
    7.29 ( 28.20 )
    -2.70 ( 18.99 )
        Change at Day 1 Cycle 26 (n=16,31)
    1.56 ( 24.95 )
    -2.15 ( 21.51 )
        Change at Day 1 Cycle 28 (n=14,23)
    1.79 ( 16.72 )
    1.81 ( 21.17 )
        Change at Day 1 Cycle 30 (n=13,21)
    5.77 ( 16.45 )
    3.17 ( 21.81 )
        Change at Day 1 Cycle 32 (n=12,22)
    0.00 ( 18.46 )
    0.38 ( 17.91 )
        Change at Day 1 Cycle 34 (n=11,20)
    0.00 ( 20.07 )
    2.50 ( 19.70 )
        Change at Day 1 Cycle 36 (n=11,20)
    -1.52 ( 15.73 )
    1.67 ( 20.52 )
        Change at Day 1 Cycle 38 (n=11,18)
    2.27 ( 21.11 )
    3.70 ( 20.66 )
        Change at Day 1 Cycle 40 (n=11,18)
    5.30 ( 21.50 )
    1.39 ( 19.85 )
        Change at Day 1 Cycle 42 (n=8,18)
    0.00 ( 17.25 )
    2.31 ( 20.37 )
        Change at Day 1 Cycle 44 (n=8,16)
    2.08 ( 18.23 )
    3.65 ( 19.95 )
        Change at Day 1 Cycle 46 (n=8,17)
    2.08 ( 25.88 )
    2.45 ( 21.60 )
        Change at Day 1 Cycle 48 (n=7,14)
    7.14 ( 15.54 )
    4.17 ( 20.35 )
        Change at Day 1 Cycle 50 (n=7,11)
    -2.38 ( 17.16 )
    3.03 ( 21.82 )
        Change at Day 1 Cycle 52 (n=6,10)
    8.33 ( 12.91 )
    -3.33 ( 16.76 )
        Change at Day 1 Cycle 54 (n=3,8)
    -2.78 ( 12.73 )
    0.00 ( 22.27 )
        Change at Day 1 Cycle 56 (n=2,3)
    4.17 ( 5.89 )
    2.78 ( 4.81 )
        Change at Day 1 Cycle 58 (n=1,2)
    0.00 ( 99999 )
    0.00 ( 0.00 )
        Change at Day 1 Cycle 60 (n=1,1)
    8.33 ( 99999 )
    0.00 ( 99999 )
        Change at Day 1 Cycle 62 (n=1,1)
    -8.33 ( 99999 )
    0.00 ( 99999 )
        Change at Day 1 Cycle 64 (n=0,1)
    9999 ( 9999 )
    0.00 ( 99999 )
        Change at TDV (n=74,149)
    -14.53 ( 26.28 )
    -13.37 ( 25.42 )
    No statistical analyses for this end point

    Secondary: Part 2: Overall Satisfaction with Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)

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    End point title
    		 Part 2: Overall Satisfaction with Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) [23]
    End point description
    Modified SWT scale of the CTSQ consisted of seven items that measured seven domains related to satisfaction with cancer therapy. These include worthwhile, difficulty, benefits, feelings about side effects, form of therapy, overall satisfaction, and if participants would choose the therapy taking everything into consideration. Each domain is rated on a 5-point scale, with 1 representing the worst response and 5 representing the best response, except in the case of one reverse-scored item. Mean of the items were linearly transformed to obtain scores from 0-100, where 100 was the best possible score. Higher scores indicate higher satisfaction. FAS included all randomized participants, with participants grouped according to their assigned treatment. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point. Here, data for ‘overall satisfaction’ domain has been presented.
    End point type
    Secondary
    End point timeframe
    Day 1 Cycle 3 or TDV (if treatment discontinued at any visit before Cycle 3) (Cycle length = 21 days)
    Notes
    [23] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    98
    191
    Units: score on a scale
    arithmetic mean (standard deviation)
        Day 1 Cycle 3 (n=83,162)
    77.29 ( 16.08 )
    75.56 ( 18.61 )
        TDV (n=15,29)
    50.67 ( 19.90 )
    61.21 ( 19.81 )
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Participants by Their Responses to AE’s Burden Over Time, Assessed by the Treatment-related Symptom Burden Item from the EORTC IL57

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    End point title
    		 Part 2: Percentage of Participants by Their Responses to AE’s Burden Over Time, Assessed by the Treatment-related Symptom Burden Item from the EORTC IL57 [24]
    End point description
    The overall patient-reported AE burden was assessed using a single item from the EORTC IL57 questionnaire i.e "To what extent have you been troubled with side-effects from your treatment?" The questions were answered on a 4-point Likert scale, where 1="Not at all" to 4="Very much". Higher scores indicated greater AE burden. Percentages have been rounded to one decimal place. FAS included all randomized participants, with participants grouped according to their assigned treatment. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point. 9999 = No participants were analyzed at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, and 64 (Cycle length = 21 days)
    Notes
    [24] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    113
    238
    Units: percentage of participants
    number (not applicable)
        Baseline - Not at all (n=113,238)
    49.6
    56.7
        Baseline - A little (n=113,238)
    36.3
    28.6
        Baseline - Quite a bit (n=113,238)
    8.0
    10.1
        Baseline - Very much (n=113,238)
    6.2
    4.6
        Day 1 Cycle 2 - Not at all (n=108,222)
    47.2
    49.5
        Day 1 Cycle 2 - A little (n=108,222)
    39.8
    35.6
        Day 1 Cycle 2 - Quite a bit (n=108,222)
    9.3
    12.6
        Day 1 Cycle 2 - Very much (n=108,222)
    3.7
    2.3
        Day 1 Cycle 3 - Not at all (n=88,184)
    43.2
    46.7
        Day 1 Cycle 3 - A little (n=88,184)
    45.5
    41.8
        Day 1 Cycle 3 - Quite a bit (n=88,184)
    10.2
    8.7
        Day 1 Cycle 3 - Very much (n=88,184)
    1.1
    2.7
        Day 1 Cycle 4 - Not at all (n=82,169)
    48.8
    46.7
        Day 1 Cycle 4 - A little (n=82,169)
    36.6
    36.1
        Day 1 Cycle 4 - Quite a bit (n=82,169)
    14.6
    15.4
        Day 1 Cycle 4 - Very much (n=82,169)
    0
    1.8
        Day 1 Cycle 5 - Not at all (n=64,136)
    56.3
    55.9
        Day 1 Cycle 5 - A little (n=64,136)
    35.9
    36.0
        Day 1 Cycle 5 - Quite a bit (n=64,136)
    7.8
    5.9
        Day 1 Cycle 5 - Very much (n=64,136)
    0
    2.2
        Day 1 Cycle 6 - Not at all (n=59,122)
    54.2
    49.2
        Day 1 Cycle 6 - A little (n=59,122)
    37.3
    40.2
        Day 1 Cycle 6 - Quite a bit (n=59,122)
    8.5
    8.2
        Day 1 Cycle 6 - Very much (n=59,122)
    0
    2.5
        Day 1 Cycle 8 - Not at all (n=48,96)
    62.5
    58.3
        Day 1 Cycle 8 - A little (n=48,96)
    33.3
    37.5
        Day 1 Cycle 8 - Quite a bit (n=48,96)
    4.2
    4.2
        Day 1 Cycle 10 - Not at all (n=42,81)
    66.7
    54.3
        Day 1 Cycle 10 - A little (n=42,81)
    28.6
    44.4
        Day 1 Cycle 10 - Quite a bit (n=42,81)
    4.8
    1.2
        Day 1 Cycle 12 - Not at all (n=36,70)
    63.9
    50.0
        Day 1 Cycle 12 - A little (n=36,70)
    30.6
    45.7
        Day 1 Cycle 12 - Quite a bit (n=36,70)
    5.6
    4.3
        Day 1 Cycle 14 - Not at all (n=31,60)
    61.3
    53.3
        Day 1 Cycle 14 - A little (n=31,60)
    25.8
    45.0
        Day 1 Cycle 14 - Quite a bit (n=31,60)
    12.9
    1.7
        Day 1 Cycle 16 - Not at all (n=28,53)
    60.7
    56.6
        Day 1 Cycle 16 - A little (n=28,53)
    28.6
    35.8
        Day 1 Cycle 16 - Quite a bit (n=28,53)
    10.7
    7.5
        Day 1 Cycle 18 - Not at all (n=23,50)
    69.6
    58.0
        Day 1 Cycle 18 - A little (n=23,50)
    30.4
    36.0
        Day 1 Cycle 18 - Quite a bit (n=23,50)
    0
    6.0
        Day 1 Cycle 20 - Not at all (n=21,44)
    71.4
    59.1
        Day 1 Cycle 20 - A little (n=21,44)
    28.6
    31.8
        Day 1 Cycle 20 - Quite a bit (n=21,44)
    0
    9.1
        Day 1 Cycle 22 - Not at all (n=18,36)
    55.6
    52.8
        Day 1 Cycle 22 - A little (n=18,36)
    38.9
    36.1
        Day 1 Cycle 22 - Quite a bit (n=18,36)
    5.6
    11.1
        Day 1 Cycle 24 - Not at all (n=16,34)
    75.0
    55.9
        Day 1 Cycle 24 - A little (n=16,34)
    25.0
    38.2
        Day 1 Cycle 24 - Quite a bit (n=16,34)
    0
    5.9
        Day 1 Cycle 26 - Not at all (n=15,31)
    73.3
    51.6
        Day 1 Cycle 26 - A little (n=15,31)
    26.7
    41.9
        Day 1 Cycle 26 - Quite a bit (n=15,31)
    0
    6.5
        Day 1 Cycle 28 - Not at all (n=14,23)
    64.3
    56.5
        Day 1 Cycle 28 - A little (n=14,23)
    35.7
    39.1
        Day 1 Cycle 28 - Quite a bit (n=14,23)
    0
    4.3
        Day 1 Cycle 30 - Not at all (n=13,20)
    69.2
    70.0
        Day 1 Cycle 30 - A little (n=13,20)
    30.8
    25.0
        Day 1 Cycle 30 - Quite a bit (n=13,20)
    0
    5.0
        Day 1 Cycle 32 - Not at all (n=12,22)
    50.0
    59.1
        Day 1 Cycle 32 - A little (n=12,22)
    41.7
    36.4
        Day 1 Cycle 32 - Quite a bit (n=12,22)
    8.3
    4.5
        Day 1 Cycle 34 - Not at all (n=11,20)
    72.7
    65.0
        Day 1 Cycle 34 - A little (n=11,20)
    27.3
    35.0
        Day 1 Cycle 36 - Not at all (n=11,20)
    63.6
    65.0
        Day 1 Cycle 36 - A little (n=11,20)
    36.4
    35.0
        Day 1 Cycle 38 - Not at all (n=11,18)
    72.7
    61.1
        Day 1 Cycle 38 - A little (n=11,18)
    27.3
    33.3
        Day 1 Cycle 38 - Quite a bit (n=11,18)
    0
    5.6
        Day 1 Cycle 40 - Not at all (n=11,18)
    72.7
    55.6
        Day 1 Cycle 40 - A little (n=11,18)
    27.3
    38.9
        Day 1 Cycle 40 - Quite a bit (n=11,18)
    0
    5.6
        Day 1 Cycle 42 - Not at all (n=8,18)
    75.0
    66.7
        Day 1 Cycle 42 - A little (n=8,18)
    25.0
    33.3
        Day 1 Cycle 44 - Not at all (n=8,16)
    75.0
    68.8
        Day 1 Cycle 44 - A little (n=8,16)
    25.0
    31.3
        Day 1 Cycle 46 - Not at all (n=8,17)
    87.5
    76.5
        Day 1 Cycle 46 - A little (n=8,17)
    0
    23.5
        Day 1 Cycle 46 - Quite a bit (n=8,17)
    12.5
    0
        Day 1 Cycle 48 - Not at all (n=7,14)
    100
    71.4
        Day 1 Cycle 48 - A little (n=7,14)
    0
    28.6
        Day 1 Cycle 50 - Not at all (n=7,11)
    100
    63.6
        Day 1 Cycle 50 - A little (n=7,11)
    0
    36.4
        Day 1 Cycle 52 - Not at all (n=6,10)
    100
    60.0
        Day 1 Cycle 52 - A little (n=6,10)
    0
    40.0
        Day 1 Cycle 54 - Not at all (n=3,8)
    100
    50.0
        Day 1 Cycle 54 - A little (n=3,8)
    0
    50.0
        Day 1 Cycle 56 - Not at all (n=2,3)
    100
    0
        Day 1 Cycle 56 - A little (n=2,3)
    0
    100
        Day 1 Cycle 58 - Not at all (n=1,2)
    100
    50.0
        Day 1 Cycle 58 - A little (n=1,2)
    0
    50.0
        Day 1 Cycle 60 - Not at all (n=1,1)
    100
    0
        Day 1 Cycle 60 - A little (n=1,1)
    0
    100
        Day 1 Cycle 62 - Not at all (n=1,1)
    100
    0
        Day 1 Cycle 62 - A little (n=1,1)
    0
    100
        Day 1 Cycle 64 - A little (n=0,1)
    9999
    100
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration

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    End point title
    		 Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration [25]
    End point description
    The percentage of ADA-positive participants after atezolizumab administration was reported. Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Safety-evaluable population included all participants who received at least one dose of atezolizumab (IV or SC), with participants grouped according to treatment received. Number analyzed is the number of participants with data available for analysis. Percentages have been rounded to one decimal place.
    End point type
    Secondary
    End point timeframe
    From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months)
    Notes
    [25] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    112
    228
    Units: percentage of participants
        number (not applicable)
    14.3
    20.6
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration

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    End point title
    		 Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration [26]
    End point description
    The percentage of ADA-positive participants after atezolizumab SC formulated with rHuPH20 administration was reported. Participants who received atezolizumab SC formulated with rHuPH20 were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following rHuPH20 exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Safety-evaluable population included all participants who received at least one dose of atezolizumab SC formulated with rHuPH20. Number analyzed is the number of participants with data available for analysis. Percentages have been rounded to one decimal place.
    End point type
    Secondary
    End point timeframe
    From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months)
    Notes
    [26] - 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: No statistical analysis for this endpoint.
    End point values
    		 Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    228
    Units: percentage of participants
        number (not applicable)
    5.7
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Health Care Professionals (HCPs) by Their Response to Question 2 of HCP SC Versus IV Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of Health Care Professionals (HCPs) by Their Response to Question 2 of HCP SC Versus IV Perspective Questionnaire
    End point description
    The HCP SC versus IV Perspective Questionnaire consisted of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 2 is being reported here: Question 2: Which formulation of atezolizumab (SC or IV) do you think is more convenient for you? Responses to this question are reported in the data table. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'first participant in [FPI]' date to 'last participant last visit [LPLV]' for Part 2). Number analyzed included HCPs who completed Question 2 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    50
    Units: percentage of HCPs
    number (not applicable)
        Atezolizumab SC is much more convenient
    24.0
        Atezolizumab SC is a little more convenient
    16.0
        Both formulations are equally convenient
    26.0
        Atezolizumab IV is a little more convenient
    12.0
        Atezolizumab IV is much more convenient
    22.0
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Versus IV Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Versus IV Perspective Questionnaire
    End point description
    The HCP SC versus IV Perspective Questionnaire consisted of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 3 is being reported here: Question 3: If used in routine practice, do you think administering atezolizumab SC could save staff time compared to atezolizumab IV? The responses to this question could be Yes; No; Unsure. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Number analyzed included HCPs who completed Question 3 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 44.7 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    50
    Units: percentage of HCPs
    number (not applicable)
        Yes
    74.0
        Unsure
    14.0
        No
    12.0
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Versus IV Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Versus IV Perspective Questionnaire
    End point description
    HCP SC versus IV Perspective Questionnaire consisted of 5 items evaluating number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as an IV infusion and as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 4 is being reported here: Question 4: Overall, were you more satisfied with atezolizumab SC or atezolizumab IV? The responses included: More satisfied with atezolizumab SC; Equally satisfied with both formulations; More satisfied with atezolizumab IV. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Number analyzed included HCPs who completed Question 4 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 44.7 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    50
    Units: percentage of HCPs
    number (not applicable)
        More satisfied with atezolizumab SC
    32.0
        Equally satisfied with both formulations
    38.0
        More satisfied with atezolizumab IV
    30.0
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of HCPs by Their Response to Question 2 of the HCP SC Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of HCPs by Their Response to Question 2 of the HCP SC Perspective Questionnaire
    End point description
    The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 2 is being reported here: Question 2: Do you think atezolizumab SC is convenient? The responses to this question could be: Yes; No; and Unsure. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place. Number analyzed included HCPs who completed Question 2 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 44.7 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    84
    Units: percentage of HCPs
    number (not applicable)
        Yes
    78.6
        Unsure
    14.3
        No
    7.1
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Perspective Questionnaire
    End point description
    The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 3 is being reported here: Question 3: Overall, how easy did you find atezolizumab SC administration? The responses to this question could be: Very easy; Fairly easy; Not at all easy. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place. Number analyzed included HCPs who completed Question 3 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 44.7 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    84
    Units: percentage of HCPs
    number (not applicable)
        Very easy
    54.8
        Fairly easy
    34.5
        Not at all easy
    10.7
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Perspective Questionnaire

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    End point title
    		 Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Perspective Questionnaire
    End point description
    The HCP SC Perspective Questionnaire consisted of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction. HCPs who administered at least three doses of atezolizumab as a SC injection across all participants in Part 2 of this study responded to this questionnaire, of which question 4 is being reported here: Question 4: Overall, how satisfied were you with atezolizumab SC? The responses to this question could be: Very satisfied; Satisfied; Dissatisfied; Very dissatisfied. HCPs were allowed to complete the questionnaire until the last participant completed their assessments (duration between the 'FPI in' date to 'LPLV' for Part 2). Percentages have been rounded to one decimal place. Number analyzed included HCPs who completed Question 4 of the questionnaire.
    End point type
    Secondary
    End point timeframe
    After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 44.7 months)
    End point values
    		 Part 2: Atezolizumab IV/Atezolizumab SC
    Number of subjects analysed
    84
    Units: percentage of HCPs
    number (not applicable)
        Very satisfied
    34.5
        Satisfied
    50.0
        Dissatisfied
    13.1
        Very dissatisfied
    2.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From initiation of study treatment up to approximately 69 months in Part 1 and up to approximately 44.7 months in Part 2
    Adverse event reporting additional description
    Safety-evaluable population included all participants who received at least one dose of atezolizumab (IV or SC), with participants grouped according to treatment received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection on Cycle 1 Day 1 (1 cycle=21 days), followed by atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of subsequent cycles until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, co-mixed with rHuPH20, as SC injection, Q2W, on Day 1 of the first 3 cycles (Cycle 1-3=14 days), followed by atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg
    Reporting group description
    		 Participants received atezolizumab, 1800 mg, co-mixed with rHuPH20, as SC injection, Q3W, on Day 1 of first 3 cycles, followed by atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 for subsequent cycles (1 cycle=21 days) until PD, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants received atezolizumab, 1875 mg, co-formulated with rHuPH20, as SC injection, on Day 1 of each cycle (1 cycle=21 days) until PD, loss of clinical benefit, or unacceptable toxicity.

    Serious adverse events
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 13 (15.38%)
    4 / 15 (26.67%)
    8 / 39 (20.51%)
    35 / 124 (28.23%)
    50 / 247 (20.24%)
         number of deaths (all causes)
    4
    6
    19
    97
    206
         number of deaths resulting from adverse events
    1
    1
    2
    9
    17
    Vascular disorders
    Orthostatic hypotension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Fall
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune myocarditis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    4 / 247 (1.62%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    3 / 247 (1.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Epilepsy
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Renal and urinary disorders
    Nephropathy
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    6 / 124 (4.84%)
    8 / 247 (3.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    Tracheobronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    3 / 247 (1.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    COVID-19
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    4 / 124 (3.23%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    4 / 247 (1.62%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Enteritis infectious
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    2 / 247 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    Pneumonia bacterial
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    3 / 124 (2.42%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1 Cohort 1: Atezolizumab SC Co-mix 1800 mg Part 1 Cohort 2: Atezolizumab SC Co-mix 1200 mg Part 1 Cohort 3: Atezolizumab SC Co-mix 1800 mg Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 13 (100.00%)
    12 / 15 (80.00%)
    31 / 39 (79.49%)
    91 / 124 (73.39%)
    204 / 247 (82.59%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hair follicle tumour benign
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Melanocytic naevus
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    4 / 39 (10.26%)
    3 / 124 (2.42%)
    3 / 247 (1.21%)
         occurrences all number
    0
    0
    5
    10
    5
    Venous thrombosis limb
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Oedema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    1
    0
    1
    0
    1
    Pyrexia
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    6 / 124 (4.84%)
    12 / 247 (4.86%)
         occurrences all number
    3
    1
    1
    8
    16
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    2 / 124 (1.61%)
    4 / 247 (1.62%)
         occurrences all number
    0
    0
    3
    2
    4
    Asthenia
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 15 (20.00%)
    7 / 39 (17.95%)
    9 / 124 (7.26%)
    19 / 247 (7.69%)
         occurrences all number
    5
    3
    12
    11
    19
    Chills
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    2
    0
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
    11 / 39 (28.21%)
    16 / 124 (12.90%)
    31 / 247 (12.55%)
         occurrences all number
    2
    3
    14
    20
    33
    Injection site erythema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    1
    0
    0
    1
    Gait disturbance
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences all number
    1
    0
    0
    1
    3
    Injection site inflammation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 39 (5.13%)
    9 / 124 (7.26%)
    11 / 247 (4.45%)
         occurrences all number
    0
    2
    3
    9
    14
    Injection site reaction
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
    2 / 39 (5.13%)
    0 / 124 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    3
    1
    4
    0
    15
    Mucosal inflammation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    3 / 39 (7.69%)
    1 / 124 (0.81%)
    5 / 247 (2.02%)
         occurrences all number
    0
    1
    3
    1
    5
    Xerosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    1 / 124 (0.81%)
    3 / 247 (1.21%)
         occurrences all number
    1
    0
    2
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    5 / 39 (12.82%)
    20 / 124 (16.13%)
    26 / 247 (10.53%)
         occurrences all number
    1
    2
    5
    21
    27
    Cough
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 15 (20.00%)
    7 / 39 (17.95%)
    9 / 124 (7.26%)
    33 / 247 (13.36%)
         occurrences all number
    6
    3
    10
    9
    37
    Dysphonia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    1 / 124 (0.81%)
    4 / 247 (1.62%)
         occurrences all number
    1
    1
    1
    1
    4
    Haemoptysis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    3 / 39 (7.69%)
    3 / 124 (2.42%)
    7 / 247 (2.83%)
         occurrences all number
    0
    2
    3
    3
    9
    Dyspnoea exertional
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    1
    0
    1
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences all number
    0
    4
    0
    2
    1
    Pleuritic pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    1
    0
    0
    0
    1
    Productive cough
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    5 / 247 (2.02%)
         occurrences all number
    1
    1
    0
    2
    6
    Pulmonary embolism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    8 / 124 (6.45%)
    8 / 247 (3.24%)
         occurrences all number
    2
    1
    0
    8
    8
    Depression
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    1 / 247 (0.40%)
         occurrences all number
    1
    1
    0
    2
    1
    Anxiety
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    2 / 124 (1.61%)
    5 / 247 (2.02%)
         occurrences all number
    1
    0
    1
    2
    5
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    4 / 39 (10.26%)
    13 / 124 (10.48%)
    23 / 247 (9.31%)
         occurrences all number
    0
    2
    5
    14
    28
    Amylase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    5 / 39 (12.82%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    2
    6
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    5 / 39 (12.82%)
    10 / 124 (8.06%)
    24 / 247 (9.72%)
         occurrences all number
    0
    0
    5
    12
    25
    Blood albumin decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    0
    3
    0
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    4 / 39 (10.26%)
    7 / 124 (5.65%)
    20 / 247 (8.10%)
         occurrences all number
    0
    1
    4
    7
    21
    Blood magnesium decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    2 / 247 (0.81%)
         occurrences all number
    1
    1
    1
    0
    3
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    6 / 124 (4.84%)
    12 / 247 (4.86%)
         occurrences all number
    0
    0
    2
    6
    16
    Blood glucose increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    3 / 39 (7.69%)
    7 / 124 (5.65%)
    6 / 247 (2.43%)
         occurrences all number
    1
    1
    4
    8
    8
    Blood cholesterol increased
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
    5 / 39 (12.82%)
    1 / 124 (0.81%)
    3 / 247 (1.21%)
         occurrences all number
    3
    3
    8
    2
    3
    Blood bilirubin increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    2 / 39 (5.13%)
    2 / 124 (1.61%)
    1 / 247 (0.40%)
         occurrences all number
    1
    1
    4
    9
    2
    Lipase increased
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    5 / 39 (12.82%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    5
    3
    6
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 39 (0.00%)
    4 / 124 (3.23%)
    7 / 247 (2.83%)
         occurrences all number
    0
    2
    0
    4
    7
    Blood triglycerides increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    3 / 124 (2.42%)
    7 / 247 (2.83%)
         occurrences all number
    1
    0
    0
    3
    15
    Blood sodium decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    4 / 39 (10.26%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    2
    5
    0
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences all number
    0
    0
    4
    4
    0
    Weight decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    2 / 39 (5.13%)
    6 / 124 (4.84%)
    15 / 247 (6.07%)
         occurrences all number
    1
    2
    2
    7
    18
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Lack of injection site rotation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injection related reaction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    0 / 124 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    0
    0
    3
    0
    9
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    3 / 247 (1.21%)
         occurrences all number
    0
    1
    1
    0
    3
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    1
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    5 / 124 (4.03%)
    5 / 247 (2.02%)
         occurrences all number
    1
    0
    3
    5
    6
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    7 / 124 (5.65%)
    17 / 247 (6.88%)
         occurrences all number
    3
    0
    0
    7
    21
    Dysgeusia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    2
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    2 / 247 (0.81%)
         occurrences all number
    1
    0
    0
    2
    2
    Sensory loss
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 13 (23.08%)
    5 / 15 (33.33%)
    13 / 39 (33.33%)
    21 / 124 (16.94%)
    47 / 247 (19.03%)
         occurrences all number
    3
    8
    16
    30
    54
    Lymphopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    3 / 124 (2.42%)
    8 / 247 (3.24%)
         occurrences all number
    0
    1
    0
    3
    9
    Thrombocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    7 / 124 (5.65%)
    9 / 247 (3.64%)
         occurrences all number
    0
    1
    1
    7
    18
    Leukocytosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    3 / 124 (2.42%)
    3 / 247 (1.21%)
         occurrences all number
    1
    0
    0
    3
    4
    Neutropenia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    2
    0
    0
    0
    1
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 13 (30.77%)
    1 / 15 (6.67%)
    4 / 39 (10.26%)
    3 / 124 (2.42%)
    21 / 247 (8.50%)
         occurrences all number
    5
    1
    6
    4
    27
    Vomiting
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    3 / 39 (7.69%)
    3 / 124 (2.42%)
    7 / 247 (2.83%)
         occurrences all number
    2
    2
    3
    3
    7
    Dyspepsia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    3 / 124 (2.42%)
    3 / 247 (1.21%)
         occurrences all number
    1
    0
    0
    3
    3
    Nausea
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
    9 / 39 (23.08%)
    4 / 124 (3.23%)
    15 / 247 (6.07%)
         occurrences all number
    1
    4
    12
    4
    16
    Constipation
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    1 / 39 (2.56%)
    9 / 124 (7.26%)
    17 / 247 (6.88%)
         occurrences all number
    2
    2
    1
    9
    17
    Flatulence
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    3 / 124 (2.42%)
    2 / 247 (0.81%)
         occurrences all number
    0
    1
    1
    3
    3
    Dry mouth
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    4 / 247 (1.62%)
         occurrences all number
    0
    1
    0
    0
    7
    Anal haemorrhage
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    12 / 247 (4.86%)
         occurrences all number
    2
    0
    0
    1
    12
    Stomatitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    1 / 247 (0.40%)
         occurrences all number
    2
    0
    0
    1
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    1 / 124 (0.81%)
    4 / 247 (1.62%)
         occurrences all number
    0
    0
    2
    1
    4
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    3 / 39 (7.69%)
    10 / 124 (8.06%)
    13 / 247 (5.26%)
         occurrences all number
    1
    1
    3
    14
    15
    Alopecia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    1
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    4 / 39 (10.26%)
    12 / 124 (9.68%)
    14 / 247 (5.67%)
         occurrences all number
    0
    1
    7
    13
    14
    Rash erythematous
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eczema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Dry skin
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    0 / 124 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    2
    0
    2
    0
    5
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    3 / 247 (1.21%)
         occurrences all number
    1
    0
    0
    1
    3
    Renal failure
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    1 / 39 (2.56%)
    7 / 124 (5.65%)
    21 / 247 (8.50%)
         occurrences all number
    0
    2
    1
    9
    25
    Hyperthyroidism
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    0 / 39 (0.00%)
    2 / 124 (1.61%)
    7 / 247 (2.83%)
         occurrences all number
    2
    2
    0
    2
    7
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    4 / 39 (10.26%)
    4 / 124 (3.23%)
    11 / 247 (4.45%)
         occurrences all number
    0
    1
    4
    6
    13
    Arthralgia
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    7 / 39 (17.95%)
    7 / 124 (5.65%)
    18 / 247 (7.29%)
         occurrences all number
    2
    2
    10
    8
    21
    Muscle spasms
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    1 / 124 (0.81%)
    3 / 247 (1.21%)
         occurrences all number
    1
    1
    2
    1
    4
    Joint swelling
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 15 (13.33%)
    5 / 39 (12.82%)
    9 / 124 (7.26%)
    21 / 247 (8.50%)
         occurrences all number
    3
    3
    5
    9
    21
    Pain in extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    6 / 124 (4.84%)
    13 / 247 (5.26%)
         occurrences all number
    0
    1
    1
    7
    17
    Musculoskeletal pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 39 (5.13%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    4 / 247 (1.62%)
         occurrences all number
    1
    1
    0
    1
    4
    Infections and infestations
    Furuncle
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    3 / 124 (2.42%)
    13 / 247 (5.26%)
         occurrences all number
    0
    1
    1
    3
    15
    Laryngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences all number
    1
    2
    0
    1
    4
    Folliculitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    2 / 39 (5.13%)
    1 / 124 (0.81%)
    3 / 247 (1.21%)
         occurrences all number
    1
    1
    4
    1
    3
    Asymptomatic bacteriuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    10 / 124 (8.06%)
    19 / 247 (7.69%)
         occurrences all number
    0
    0
    0
    11
    19
    Conjunctivitis bacterial
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    1 / 247 (0.40%)
         occurrences all number
    0
    1
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    1
    0
    0
    0
    5
    Viral infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    8 / 124 (6.45%)
    11 / 247 (4.45%)
         occurrences all number
    2
    2
    1
    11
    15
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    3 / 124 (2.42%)
    7 / 247 (2.83%)
         occurrences all number
    3
    0
    3
    3
    7
    Sinusitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    2 / 124 (1.61%)
    4 / 247 (1.62%)
         occurrences all number
    5
    0
    2
    3
    4
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 39 (5.13%)
    5 / 124 (4.03%)
    14 / 247 (5.67%)
         occurrences all number
    0
    1
    2
    6
    15
    Hypercreatininaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    7 / 124 (5.65%)
    3 / 247 (1.21%)
         occurrences all number
    0
    0
    0
    10
    3
    Hypercalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    6 / 124 (4.84%)
    2 / 247 (0.81%)
         occurrences all number
    0
    1
    0
    9
    3
    Hypokalaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    1 / 39 (2.56%)
    6 / 124 (4.84%)
    8 / 247 (3.24%)
         occurrences all number
    1
    1
    1
    9
    9
    Hyperglycaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    3 / 39 (7.69%)
    13 / 124 (10.48%)
    12 / 247 (4.86%)
         occurrences all number
    1
    1
    3
    22
    18
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    7 / 39 (17.95%)
    13 / 124 (10.48%)
    17 / 247 (6.88%)
         occurrences all number
    0
    2
    7
    17
    18
    Hypomagnesaemia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    4 / 39 (10.26%)
    8 / 124 (6.45%)
    8 / 247 (3.24%)
         occurrences all number
    2
    0
    4
    9
    9
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    3 / 39 (7.69%)
    11 / 124 (8.87%)
    9 / 247 (3.64%)
         occurrences all number
    0
    0
    4
    15
    14
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 39 (0.00%)
    1 / 124 (0.81%)
    2 / 247 (0.81%)
         occurrences all number
    0
    2
    0
    1
    2
    Vitamin D deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 39 (2.56%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 39 (0.00%)
    0 / 124 (0.00%)
    0 / 247 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 15 (20.00%)
    8 / 39 (20.51%)
    15 / 124 (12.10%)
    31 / 247 (12.55%)
         occurrences all number
    2
    3
    8
    16
    32

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jun 2019
    Amendment v2: 1. Subcutaneous site of first drug administration for Cohort 3 was changed from thigh to abdomen to accommodate participant convenience, increased participant privacy, and possible administration of higher drug volume. 2. Study drug dosage for Cohort 3 was changed from 2400 mg Q4W to 1800 mg Q3W to assess the alternate administration site (abdomen). 3. Enrollment for Cohort 3 was increased to approximately 20-30 participants to provide enough participants who could be assessed for feasibility of abdominal administration.
    30 Mar 2020
    Amendment v3: No changes impacted study conduct.
    28 Aug 2020
    Amendment v4: 1. A randomized control arm comprising of participants treated with atezolizumab IV as per standard of care was added in Part 2 and enrollment was expanded to include an extension in China. 2. Investigational treatment in Part 2 was modified to atezolizumab monotherapy and inclusion criteria modified to include participants in whom platinum therapy had failed, to allow for assessment of atezolizumab SC without confounding factors associated with use in combination with chemotherapy. 3. Model-predicted area under the atezolizumab AUC at Cycle 1 (AUCcycle 1) was added as a key secondary endpoint. 4. Additional secondary PK objectives for Part 2 were added to evaluate exposure following administration of atezolizumab SC compared with atezolizumab IV. 5. Duration of response was added as an efficacy endpoint in Part 2. 6. Patient- and health care professional-reported experience assessments was added to Part 2 to provide a more comprehensive characterization of the SC formulation.
    10 Feb 2021
    Amendment v5: 1. A new co-primary PK endpoint was introduced (model-predicted AUC0-21d at Cycle 1). 2. Number of participants enrolled in Part 2 was increased to 327 to accommodate the new co-primary PK endpoint.
    25 Feb 2022
    Amendment v6: 1. Adverse event management guidelines were updated to align with the atezolizumab investigator’s brochure, version 18. 2. References to an extended recruitment in China was removed. 3. Estimand language in Section 6.6.2 was corrected to match the definition of Per Protocol PK analysis population provided in Section 6.2.2. 4. Benefit-risk assessment and guidance on concomitant administration of severe acute respiratory syndrome coronavirus 2 vaccines with atezolizumab was added. 5. Responsibilities of the Principal Investigator and the role of the medical monitor in determining participant eligibility was clarified.
    07 Feb 2023
    Amendment v7: 1. The list of identified risks for atezolizumab was revised to include pericardial disorders. 2. The list of identified risks for atezolizumab was revised to include myelitis and facial paresis. 3. Hemophagocytic lymphohistiocytosis was updated from a potential risk to an identified risk associated with atezolizumab and language has been revised accordingly. 4. The list of adverse events of special interest (AESIs) was revised to include myelitis and facial paresis. 5. A description of the technical and organizational security measures taken to protect personal data was added to align with CTR requirements. 6. Appendix 8 was revised to indicate that caution should be used when considering atezolizumab for participants who have previously experienced a pericardial disorder while receiving another immunostimulatory anti-cancer agent.
    18 Mar 2024
    Amendment v8: 1. The list of approved indications for atezolizumab was updated to include alveolar soft part sarcoma. 2. The adverse event management guidelines were streamlined by removing standard of care information and restructured for consistency with regulatory guidelines and industry standards.

    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
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