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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

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 May 2023
    First version publication date
    12 May 2023
    Other versions

    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,
    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, genentech@druginfo.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
    Interim
    Date of interim/final analysis
    21 Apr 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Apr 2022
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of Part 1 of the study is to determine the dose of atezolizumab (atezo) given as subcutameous (SC) injection that is predicted to yield drug exposure that is comparable to that of atezolizumab intravenous (IV) infusion. The purpose of Part 2 of the study is 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
    21 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
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    New Zealand: 17
    Country: Number of subjects enrolled
    Spain: 37
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    United Kingdom: 2
    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
    Chile: 50
    Country: Number of subjects enrolled
    China: 10
    Country: Number of subjects enrolled
    Thailand: 69
    Country: Number of subjects enrolled
    Argentina: 7
    Country: Number of subjects enrolled
    Brazil: 22
    Country: Number of subjects enrolled
    Costa Rica: 8
    Country: Number of subjects enrolled
    Guatemala: 7
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Peru: 18
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Russian Federation: 44
    Country: Number of subjects enrolled
    Turkey: 54
    Country: Number of subjects enrolled
    Ukraine: 28
    Country: Number of subjects enrolled
    South Africa: 3
    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 cancer immunotherapy (CIT)-naïve participants with non-small cell lung cancer (NSCLC) who failed prior platinum-based therapy took part in the study in 24 countries from 21 Dec 2018 to 21 Apr 2022. The study is ongoing.

    Pre-assignment
    Screening details
    		 The study has 2 parts-Part 1 and Part 2. Participants received atezolizumab [co-mixed with recombinant human hyaluronidase (rHuPH20)] at the assigned dose as SC and IV in Part 1 and atezolizumab [co-formulated with recombinant human hyaluronidase (rHuPH20)] as SC or IV in Part 2.

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

    Arms
    Are arms mutually exclusive
    Yes

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

    Investigational medicinal product name
    rHuPH20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    rHuPH20 will be administered as per the schedule specified in the cohort 1 for Part 1.

    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 SC co-mix 1800 mg on Day 1 of Cycle 1.

    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 IV 1200 mg, Q3W, from Day 1 Cycle 2 for all subsequent cycles.

    Arm title
    		 Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV
    Arm description
    		 Participants received 1200 mg of atezolizumab co-mixed with rHuPH20, as SC injection, every two weeks (Q2W), for 3 cycles (Cycle 1-3=14 days), followed by 1200 mg of atezolizumab as IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267/F01
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Atezolizumab SC co-mix 1200 mg Q2W for Cycles 1-3.

    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 IV 1200 mg, Q3W, from Day 1 of Cycle 4 onwards for all subsequent cycles.

    Investigational medicinal product name
    rHuPH20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    rHuPH20 will be administered as per the schedule specified in the cohort 2 for Part 1.

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

    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 IV 1200 mg, Q3W, from Day 1 of Cycle 4 onwards for all subsequent cycles.

    Investigational medicinal product name
    rHuPH20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    rHuPH20 will be administered as per the schedule specified in the cohort 3 for Part 1.

    Arm title
    		 Part 2: Atezolizumab IV 1200 mg
    Arm description
    		 Participants will receive 1200 mg of atezolizumab, as IV infusion, Q3W, on Day 1 of each 21-day cycle until disease progression, 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 IV 1200 mg Q3W on Day 1 of each 21 day cycle.

    Arm title
    		 Part 2: Atezolizumab SC 1875 mg
    Arm description
    		 Participants will receive 1875 mg of atezolizumab co-formulated with rHuPH20, as SC injection, on Day 1 of each 21-day cycle until disease progression, 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 co-formulated with rHuPH20, SC 1875 mg Q3W on each 21 day cycle.

    Number of subjects in period 1
    		Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Started
    13
    15
    39
    124
    247
    Completed
    6
    5
    1
    0
    0
    Not completed
    7
    10
    38
    124
    247
         Death
    3
    6
    8
    37
    86
         Progressive Disease
    -
    -
    1
    -
    -
         Ongoing
    3
    3
    26
    83
    158
         Withdrawal by Subject
    1
    1
    3
    4
    2
         Lost to follow-up
    -
    -
    -
    -
    1

    Baseline characteristics

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

    Reporting group title
    Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV
    Reporting group description
    		 Participants received 1200 mg of atezolizumab co-mixed with rHuPH20, as SC injection, every two weeks (Q2W), for 3 cycles (Cycle 1-3=14 days), followed by 1200 mg of atezolizumab as IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Reporting group description
    		 Participants received 1800 mg of atezolizumab co-mixed with rHuPH20, as SC injection, every 3 weeks (Q3W), for 3 cycles (1 cycle=21 days), followed by 1200 mg of atezolizumab IV injection Q3W on Day 1 for subsequent cycles until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants will receive 1200 mg of atezolizumab, as IV infusion, Q3W, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants will receive 1875 mg of atezolizumab co-formulated with rHuPH20, as SC injection, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

    Reporting group values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV 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: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.7 ( 9.9 ) 62.9 ( 11.8 ) 65.2 ( 10.7 ) 64.4 ( 9.8 ) 62.2 ( 9.8 ) -
    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
    Ethnicity (NIH/OMB)
    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: Atezo SC 1800 mg then Atezo 1200mg IV
    Reporting group description
    		 Participants received 1800 milligrams (mg) of atezolizumab co-mixed with rHuPH20 as SC injection on Day 1 of Cycle 1 (1 cycle=21 days), followed by 1200 mg of atezolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of subsequent cycles until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV
    Reporting group description
    		 Participants received 1200 mg of atezolizumab co-mixed with rHuPH20, as SC injection, every two weeks (Q2W), for 3 cycles (Cycle 1-3=14 days), followed by 1200 mg of atezolizumab as IV infusion, Q3W, on Day 1 of subsequent cycles (1 cycle=21 days) until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Reporting group description
    		 Participants received 1800 mg of atezolizumab co-mixed with rHuPH20, as SC injection, every 3 weeks (Q3W), for 3 cycles (1 cycle=21 days), followed by 1200 mg of atezolizumab IV injection Q3W on Day 1 for subsequent cycles until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants will receive 1200 mg of atezolizumab, as IV infusion, Q3W, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants will receive 1875 mg of atezolizumab co-formulated with rHuPH20, as SC injection, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

    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 and did not have protocol deviations that could affect PK results. Overall number analysed 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: Descriptive statistics were not planned 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: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Number of subjects analysed
    13
    15
    35
    Units: micrograms per milli liter (μg/mL)
    geometric mean (geometric coefficient of variation)
        Ctrough at Cycle 1
    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. Overall number analyzed is the number of participants with data available for analysis.
    End point type
    Primary
    End point timeframe
    Predose on Day 1 of Cycle 2 (Cycle length=21 days for cohorts 1 and 3 and 14 days for cohort 2)
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    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)
        Ctrough at Cycle 1
    85.4 ( 34.1 )
    89.4 ( 127.1 )
    Statistical analysis title
    		 Analysis of Co-primary Endpoint Ctrough
    Statistical analysis description
    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.
    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
    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

    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 [4]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab (atezolizumab SC or atezolizumab IV) and had atleast 1 evaluable post dose PK sample. Overall number analysed 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
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: micrograms per 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
    Statistical analysis description
    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 greater than or equal to (≥) the non-inferiority margin 0.8.
    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
    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

    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 [5]
    End point description
    PK-evaluable population included all participants who received at least one dose of atezolizumab (atezolizumab SC or atezolizumab IV) and had atleast 1 evaluable post dose PK sample that could affect PK results. Overall number analysed 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
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    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 [6]
    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 that could affect PK results. Overall number analysed 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
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    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 [7]
    End point description
    PK -evaluable population included all participants who received at least one dose of atezolizumab and had atleast 1 evaluable post dose PK sample that could affect PK results. Overall number analysed 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
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 1 and hence included only Part 1 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Number of subjects analysed
    13
    14
    30
    Units: day*ug/mL
    geometric mean (geometric coefficient of variation)
        AUClast at Cycle 1
    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 [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. Here 99999 indicates participants were not analysed for this endpoint at the given timepoint; 9999 indicates the data was not evaluable as all the samples were below lower limit of quantification (BLLQ). Cohorts 1,3 cycle length =21days; cohort 2=14days. Overall number analysed is the number of participants with data available for analysis at a specified timepoint.
    End point type
    Secondary
    End point timeframe
    Cohort 1: Pre&postdose:D1 &postdose: D3,8 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
    [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: The endpoint is specific for Part 1 and hence included only Part 1 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Number of subjects analysed
    13
    15
    39
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1, Day 1: Pre-dose (13,15,39)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        Cycle 1, Day 1: Post-dose (13,15,39)
    116 ( 57.8 )
    61.7 ( 70.9 )
    108 ( 57.6 )
        Cycle 1, Day 3: Post-dose (13,15,38)
    247 ( 40.5 )
    123 ( 44.3 )
    166 ( 45.7 )
        Cycle 1, Day 8: Post-dose (13,15,37)
    230 ( 36.6 )
    110 ( 45.0 )
    162 ( 43.5 )
        Cycle 2, Day 1: Pre-dose (0,15,35)
    99999 ( 99999 )
    77.5 ( 51.4 )
    78.3 ( 88.6 )
        Cycle 2, Day 1: Post-dose (0,0,36)
    99999 ( 99999 )
    99999 ( 99999 )
    87.7 ( 64.7 )
        Cycle 2, Day 2: Post-dose (0,0,36)
    99999 ( 99999 )
    99999 ( 99999 )
    183 ( 46.1 )
        Cycle 2, Day 4: Post-dose (0,0,34)
    99999 ( 99999 )
    99999 ( 99999 )
    245 ( 42.0 )
        Cycle 2, Day 9: Post-dose (0,0,35)
    99999 ( 99999 )
    99999 ( 99999 )
    225 ( 37.2 )
        Cycle 3, Day 1: pre-dose (0,14,33)
    99999 ( 99999 )
    104 ( 47.8 )
    123 ( 57.2 )
    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 [9]
    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. Overall number analysed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (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: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    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 1: Percentage of Participants with Adverse Events (AEs)

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    End point title
    		 Part 1: Percentage of Participants with Adverse Events (AEs) [10]
    End point description
    An AE is 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 adverse events. 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 (atezolizumab SC or atezolizumab IV)
    End point type
    Secondary
    End point timeframe
    From signing of informed consent form (ICF) until 30 days after last dose of study drug administration in Part 1 (Up to approximately 15 months)
    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: The endpoint is specific for Part 1 and hence included only Part 1 arms.
    End point values
    		 Part 1 Cohort 1: Atezo SC 1800 mg then Atezo 1200mg IV Part 1 Cohort 2: Atezo SC 1200 mg Q2W, then Atezo 1200mg IV Part 1 Cohort 3: Atezo SC 1800 mg Q3W then Atezo 1200 mg IV
    Number of subjects analysed
    13
    13
    31
    Units: Percentage of Participants
        number (not applicable)
    100
    86.7
    79.5
    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 [11]
    End point description
    An AE is 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 adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0). Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From signing of informed consent form (ICF) until 30 days after last dose of study drug administration in Part 2 (Up to approximately 72 months)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Percentage of Participants
        number (not applicable)
    Notes
    [12] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [13] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

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

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    End point title
    		 Part 2: Model Predicted Ctrough at steady State (Cthrough,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. Overall number analysed is the number of participants with data available for analysis
    End point type
    Secondary
    End point timeframe
    Atezo SC: Pre & postdose C1D1, postdose C1 Days 2,4,8, Predose C2,D1 and Predose C3,4,8,12 and 16 D1; Atezo IV: pre and postdose of C1D1, postdose C1 Days 2,4,8; Pre and postdose C2D1, Predose at 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: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    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. Overall number analysed is the number of participants with data available for analysis
    End point type
    Secondary
    End point timeframe
    Atezo SC: Pre & postdose C1D1, postdose C1 Days 2,4,8, Predose C2,D1 and Predose C3,4,8,12 and 16 D1; Atezo IV: pre and postdose of C1D1, postdose C1 Days 2,4,8; Pre and postdose C2D1, Predose at 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: The endpoint is specific for Part 2 and hence included only Part 2 arms.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    122
    246
    Units: μg.day/mL
        geometric mean (geometric coefficient of variation)
    6107 ( 27.3 )
    6163 ( 46.7 )
    No statistical analyses for this end point

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

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    End point title
    		 Part 2: Progression-Free Survival (PFS) [16]
    End point description
    PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From study start to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 72 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: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [17]
    0 [18]
    Units: months
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [17] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [18] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Overall Survival (OS)

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    End point title
    		 Part 2: Overall Survival (OS) [19]
    End point description
    OS defined as the time from study entry to death from any cause. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From study start to death from any cause (Up to approximately 72 months)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [20]
    0 [21]
    Units: months
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [20] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [21] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Duration of response (DOR)

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    End point title
    		 Part 2: Duration of response (DOR) [22]
    End point description
    DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. Objective response is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 72 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: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [23]
    0 [24]
    Units: months
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [23] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [24] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    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) [25]
    End point description
    ORR is 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 (RECIST) version (v)1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From treatment initiation until disease progression or loss of clinical benefit (Up to approximately 72 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: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [26]
    0 [27]
    Units: percentage of participants
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [26] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [27] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Overall Patient-reported 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: Overall Patient-reported AE’s Burden Over Time, Assessed by the Treatment-related Symptom Burden Item from the EORTC IL57 [28]
    End point description
    The overall patient-reported AE burden was assessed using the 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 is answered on a 4-point Likert scale where 1="Not at all" to 4="Very much". Higher scores indicates greater AE burden. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [29]
    0 [30]
    Units: score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [29] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [30] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Functioning and Global Health Status Over Time, as assessed by European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)57

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    End point title
    		 Part 2: Functioning and Global Health Status Over Time, as assessed by European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)57 [31]
    End point description
    EORTC IL57 questionnaire has10 items and covers 3 scales: physical functioning (PF), role functioning (RF) & global health status/quality of life (GHS/QoL) & 1 item from EORTC Item Library. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks & short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work & pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health & QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning & a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 =best possible score. Higher score = better outcome.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [32]
    0 [33]
    Units: score on a scale
        number (not applicable)
    Notes
    [32] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [33] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    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) [34]
    End point description
    Modified SWT scale of the CTSQ consist of seven items that measures 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 are linearly transformed to obtain scores from 0-100, where 100 =best possible score Higher scores are associated with higher satisfaction. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    Day 1 Cycle 3 or at treatment discontinuation visit (Up to approximately 72 months)
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [35]
    0 [36]
    Units: score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [35] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [36] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    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 [37]
    End point description
    Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    End point type
    Secondary
    End point timeframe
    From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months).
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [38]
    0 [39]
    Units: percentage of participants
        number (not applicable)
    Notes
    [38] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [39] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of Participants with ADAs to rHuPH20 After SC Administration Relative to the Prevalence of ADAs at Baseline

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    End point title
    		 Part 2: Percentage of Participants with ADAs to rHuPH20 After SC Administration Relative to the Prevalence of ADAs at Baseline [40]
    End point description
    End point type
    Secondary
    End point timeframe
    From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months)
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [41]
    0 [42]
    Units: percentage of participants
        number (not applicable)
    Notes
    [41] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [42] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Convenience, Ease of Administration, and Overall Satisfaction with Atezolizumab SC Assessed Using HCP Subcutaneous Perspective Questionnaire

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    End point title
    		 Part 2: Convenience, Ease of Administration, and Overall Satisfaction with Atezolizumab SC Assessed Using HCP Subcutaneous Perspective Questionnaire [43]
    End point description
    The HCP Subcutaneous Perspective Questionnaire consists 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. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    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 72 months)
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [44]
    0 [45]
    Units: participants
        number (not applicable)
    Notes
    [44] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [45] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Secondary: Part 2: Convenience, Potential Time Savings, and Overall Satisfaction with Atezolizumab SC Compared with Atezolizumab IV as Assessed Using HCP Subcutaneous Versus IV Perspective Questionnaire

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    End point title
    		 Part 2: Convenience, Potential Time Savings, and Overall Satisfaction with Atezolizumab SC Compared with Atezolizumab IV as Assessed Using HCP Subcutaneous Versus IV Perspective Questionnaire [46]
    End point description
    HCP Subcutaneous Versus IV Perspective Questionnaire consists 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. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
    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 72 months)
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is specific for Part 2 and hence included only Part 2 arms. Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    End point values
    		 Part 2: Atezolizumab IV 1200 mg Part 2: Atezolizumab SC 1875 mg
    Number of subjects analysed
    0 [47]
    0 [48]
    Units: participants
        number (not applicable)
    Notes
    [47] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    [48] - Data collection is ongoing and results will be disclosed within 1 year from Study Completion Date.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From signing of ICF to primary completion date (Up to approximately 40 months)
    Adverse event reporting additional description
    Safety-evaluable population included all participants who received at least one dose of atezolizumab (atezolizumab SC or atezolizumab IV).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Part 1 Cohort 1: Atezo SC 1800 mg Co-mix
    Reporting group description
    		 Participants received 1800 mg of atezolizumab co-mixed with rHuPH20, as SC injection on Day 1 of Cycle 1 (1 cycle=21 days), followed by 1200 mg of atezolizumab as IV infusion Q3W on Day 1 of subsequent cycles until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

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

    Reporting group title
    Part 2: Atezolizumab SC 1875 mg
    Reporting group description
    		 Participants will receive 1875 mg of atezolizumab co-formulated with rHuPH20, as SC injection, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

    Reporting group title
    Part 2: Atezolizumab IV 1200 mg
    Reporting group description
    		 Participants will receive 1200 mg of atezolizumab, as IV infusion, Q3W, on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity.

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

    Serious adverse events
    		 Part 1 Cohort 1: Atezo SC 1800 mg Co-mix Part 1 Cohort 2: Atezolizumab SC 1200mg, Q2W, Co-mix Part 2: Atezolizumab SC 1875 mg Part 2: Atezolizumab IV 1200 mg Part 1 Cohort 3: Atezolizumab SC 1800 mg, Q3W, Co-mix
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 13 (15.38%)
    4 / 15 (26.67%)
    38 / 247 (15.38%)
    22 / 124 (17.74%)
    9 / 39 (23.08%)
         number of deaths (all causes)
    3
    6
    86
    37
    8
         number of deaths resulting from adverse events
    0
    0
    2
    0
    0
    Vascular disorders
    Orthostatic Hypotension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Pyrexia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    2 / 124 (1.61%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         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%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 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%)
    2 / 247 (0.81%)
    2 / 124 (1.61%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
    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 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Haemoptysis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         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%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         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 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Investigations
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         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
    Blood Sodium Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         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
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         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
    Injury, poisoning and procedural complications
    Infusion Related Reaction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Hip Fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Head Injury
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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 / 1
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial Infarction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    4 / 247 (1.62%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Cardiac Failure Congestive
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Acute Coronary Syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Nervous system disorders
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (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
    Ischaemic Stroke
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Splenic Infarction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Abdominal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Dysphagia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         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%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         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
    Nausea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Oesophageal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (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
    Hepatobiliary disorders
    Immune-Mediated Hepatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Skin and subcutaneous tissue disorders
    Toxic Epidermal Necrolysis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    1 / 1
    0 / 0
    0 / 0
    Rash Maculo-Papular
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Renal and urinary disorders
    Tubulointerstitial Nephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (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%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Vascular Device Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (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
    Pneumonia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    5 / 247 (2.02%)
    4 / 124 (3.23%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    3 / 124 (2.42%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Lung Abscess
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (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
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Gastroenteritis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Urinary Tract Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    2 / 124 (1.61%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Pneumonia Aspiration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    Covid-19 Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    4 / 247 (1.62%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Pneumocystis Jirovecii Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         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 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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 / 1
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis Infectious
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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 / 1
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 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 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (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
    Hypokalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1 Cohort 1: Atezo SC 1800 mg Co-mix Part 1 Cohort 2: Atezolizumab SC 1200mg, Q2W, Co-mix Part 2: Atezolizumab SC 1875 mg Part 2: Atezolizumab IV 1200 mg Part 1 Cohort 3: Atezolizumab SC 1800 mg, Q3W, Co-mix
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 13 (100.00%)
    12 / 15 (80.00%)
    193 / 247 (78.14%)
    88 / 124 (70.97%)
    29 / 39 (74.36%)
    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 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    2 / 124 (1.61%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    1
    3
    2
    Venous Thrombosis Limb
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Injection Site Reaction
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
    4 / 247 (1.62%)
    0 / 124 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    3
    1
    10
    0
    4
    Oedema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Injection Site Inflammation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    25 / 247 (10.12%)
    17 / 124 (13.71%)
    9 / 39 (23.08%)
         occurrences all number
    2
    2
    26
    17
    10
    Gait Disturbance
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    Chills
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    Asthenia
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 15 (20.00%)
    16 / 247 (6.48%)
    6 / 124 (4.84%)
    6 / 39 (15.38%)
         occurrences all number
    5
    3
    16
    6
    6
    Injection Site Erythema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    1
    1
    0
    1
    Chest Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    9 / 247 (3.64%)
    8 / 124 (6.45%)
    1 / 39 (2.56%)
         occurrences all number
    0
    2
    11
    8
    2
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    4 / 247 (1.62%)
    2 / 124 (1.61%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    4
    2
    2
    Mucosal Inflammation
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    1
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 15 (6.67%)
    10 / 247 (4.05%)
    5 / 124 (4.03%)
    1 / 39 (2.56%)
         occurrences all number
    3
    1
    12
    6
    1
    Oedema Peripheral
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    3 / 247 (1.21%)
    1 / 124 (0.81%)
    2 / 39 (5.13%)
         occurrences all number
    0
    1
    3
    1
    2
    Injection Site Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    6 / 247 (2.43%)
    0 / 124 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    8
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    22 / 247 (8.91%)
    15 / 124 (12.10%)
    3 / 39 (7.69%)
         occurrences all number
    1
    2
    22
    16
    3
    Haemoptysis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    3 / 247 (1.21%)
    2 / 124 (1.61%)
    3 / 39 (7.69%)
         occurrences all number
    0
    2
    3
    2
    3
    Dyspnoea Exertional
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Dysphonia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    1 / 124 (0.81%)
    1 / 39 (2.56%)
         occurrences all number
    1
    1
    2
    1
    1
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Pleuritic Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    5 / 13 (38.46%)
    3 / 15 (20.00%)
    23 / 247 (9.31%)
    7 / 124 (5.65%)
    5 / 39 (12.82%)
         occurrences all number
    6
    3
    26
    7
    5
    Productive Cough
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    4 / 247 (1.62%)
    2 / 124 (1.61%)
    0 / 39 (0.00%)
         occurrences all number
    1
    1
    4
    2
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    8 / 247 (3.24%)
    8 / 124 (6.45%)
    0 / 39 (0.00%)
         occurrences all number
    2
    1
    8
    8
    0
    Investigations
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    17 / 247 (6.88%)
    7 / 124 (5.65%)
    3 / 39 (7.69%)
         occurrences all number
    0
    2
    17
    7
    4
    Lipase Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    1
    2
    0
    0
    3
    Weight Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    8 / 247 (3.24%)
    5 / 124 (4.03%)
    0 / 39 (0.00%)
         occurrences all number
    1
    1
    11
    5
    0
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    17 / 247 (6.88%)
    4 / 124 (3.23%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    17
    5
    2
    Blood Sodium Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    0
    0
    1
    0
    3
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    13 / 247 (5.26%)
    5 / 124 (4.03%)
    2 / 39 (5.13%)
         occurrences all number
    0
    1
    13
    5
    2
    Blood Albumin Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    0
    0
    2
    Blood Triglycerides Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Amylase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    0
    2
    0
    0
    4
    Platelet Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    3 / 39 (7.69%)
         occurrences all number
    0
    0
    0
    1
    4
    Blood Thyroid Stimulating Hormone Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Blood Creatinine Increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    4 / 124 (3.23%)
    1 / 39 (2.56%)
         occurrences all number
    1
    1
    1
    4
    1
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    9 / 247 (3.64%)
    4 / 124 (3.23%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    9
    4
    2
    Blood Cholesterol Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    3
    0
    0
    2
    Blood Magnesium Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Neutrophil Count Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    6 / 247 (2.43%)
    4 / 124 (3.23%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    6
    4
    0
    Haemoglobin Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Procedural Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cardiac disorders
    Supraventricular Tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    1
    1
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    10 / 247 (4.05%)
    5 / 124 (4.03%)
    0 / 39 (0.00%)
         occurrences all number
    2
    0
    11
    5
    0
    Dizziness
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    2 / 124 (1.61%)
    3 / 39 (7.69%)
         occurrences all number
    1
    0
    3
    2
    3
    Dysgeusia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    2
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Sensory Loss
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Neuropathy Peripheral
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    7 / 247 (2.83%)
    5 / 124 (4.03%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    9
    5
    0
    Leukocytosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    2 / 247 (0.81%)
    2 / 124 (1.61%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    2
    2
    0
    Anaemia
         subjects affected / exposed
    3 / 13 (23.08%)
    5 / 15 (33.33%)
    37 / 247 (14.98%)
    18 / 124 (14.52%)
    12 / 39 (30.77%)
         occurrences all number
    3
    5
    40
    21
    13
    Lymphopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    7 / 247 (2.83%)
    2 / 124 (1.61%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    8
    2
    0
    Eye disorders
    Periorbital Oedema
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Anal Haemorrhage
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dry Mouth
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    3 / 124 (2.42%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    3
    3
    0
    Vomiting
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    7 / 247 (2.83%)
    3 / 124 (2.42%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    7
    3
    2
    Abdominal Pain
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    9 / 247 (3.64%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    2
    0
    9
    1
    0
    Diarrhoea
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    11 / 247 (4.45%)
    3 / 124 (2.42%)
    2 / 39 (5.13%)
         occurrences all number
    2
    0
    11
    4
    2
    Nausea
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
    14 / 247 (5.67%)
    2 / 124 (1.61%)
    8 / 39 (20.51%)
         occurrences all number
    1
    4
    14
    2
    10
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    1
    0
    2
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    14 / 247 (5.67%)
    5 / 124 (4.03%)
    1 / 39 (2.56%)
         occurrences all number
    1
    2
    14
    5
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    9 / 247 (3.64%)
    8 / 124 (6.45%)
    1 / 39 (2.56%)
         occurrences all number
    1
    1
    11
    9
    1
    Alopecia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 247 (0.40%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Rash Erythematous
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Dry Skin
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    0 / 124 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    0
    3
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    8 / 247 (3.24%)
    10 / 124 (8.06%)
    4 / 39 (10.26%)
         occurrences all number
    0
    1
    8
    11
    4
    Renal and urinary disorders
    Renal Failure
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Acute Kidney Injury
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    6 / 247 (2.43%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    2
    2
    6
    1
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    13 / 247 (5.26%)
    4 / 124 (3.23%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    13
    6
    0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    16 / 247 (6.48%)
    7 / 124 (5.65%)
    2 / 39 (5.13%)
         occurrences all number
    2
    3
    16
    7
    2
    Pain In Extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    10 / 247 (4.05%)
    5 / 124 (4.03%)
    1 / 39 (2.56%)
         occurrences all number
    0
    1
    12
    5
    1
    Muscle Spasms
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    1 / 124 (0.81%)
    1 / 39 (2.56%)
         occurrences all number
    1
    1
    2
    1
    1
    Arthralgia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    15 / 247 (6.07%)
    5 / 124 (4.03%)
    4 / 39 (10.26%)
         occurrences all number
    1
    2
    18
    6
    4
    Musculoskeletal Chest Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    3 / 247 (1.21%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    1
    1
    3
    1
    0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    0
    0
    0
    0
    3
    Myalgia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    9 / 247 (3.64%)
    1 / 124 (0.81%)
    4 / 39 (10.26%)
         occurrences all number
    0
    1
    10
    1
    4
    Joint Swelling
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    11 / 247 (4.45%)
    2 / 124 (1.61%)
    1 / 39 (2.56%)
         occurrences all number
    0
    1
    13
    2
    1
    Covid-19
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    12 / 247 (4.86%)
    8 / 124 (6.45%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    12
    8
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    8 / 247 (3.24%)
    5 / 124 (4.03%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    9
    5
    0
    Furuncle
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    1 / 124 (0.81%)
    2 / 39 (5.13%)
         occurrences all number
    1
    1
    2
    1
    2
    Folliculitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Vestibular Neuronitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    4 / 247 (1.62%)
    2 / 124 (1.61%)
    2 / 39 (5.13%)
         occurrences all number
    2
    0
    4
    2
    2
    Laryngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Asymptomatic Bacteriuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Viral Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Hypomagnesaemia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 15 (0.00%)
    6 / 247 (2.43%)
    7 / 124 (5.65%)
    3 / 39 (7.69%)
         occurrences all number
    2
    0
    7
    8
    3
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    11 / 247 (4.45%)
    4 / 124 (3.23%)
    2 / 39 (5.13%)
         occurrences all number
    0
    1
    12
    5
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 15 (20.00%)
    14 / 247 (5.67%)
    12 / 124 (9.68%)
    4 / 39 (10.26%)
         occurrences all number
    0
    3
    14
    15
    4
    Hyperglycaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    7 / 247 (2.83%)
    10 / 124 (8.06%)
    2 / 39 (5.13%)
         occurrences all number
    1
    0
    8
    13
    2
    Hypokalaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    4 / 124 (3.23%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    3
    4
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    6 / 124 (4.84%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    2
    7
    0
    Vitamin D Deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hypercreatininaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    3 / 247 (1.21%)
    8 / 124 (6.45%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    5
    9
    0
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 247 (0.81%)
    1 / 124 (0.81%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    2
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    8 / 247 (3.24%)
    8 / 124 (6.45%)
    3 / 39 (7.69%)
         occurrences all number
    0
    0
    9
    10
    3
    Decreased Appetite
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 15 (20.00%)
    24 / 247 (9.72%)
    10 / 124 (8.06%)
    6 / 39 (15.38%)
         occurrences all number
    1
    3
    25
    11
    6
    Vitamin B12 Deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 247 (0.00%)
    0 / 124 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jun 2019
    Subcutaneous site of first drug administration for Cohort 3 was changed from thigh to abdomen to accommodate patient convenience, increased patient privacy, and possible administration of higher drug volume. Study drug dosage for Cohort 3 was changed from 2400 mg Q4W to 1800 mg Q3W to assess the alternate administration site (abdomen). Enrollment for Cohort 3 was increased to approximately 20-30 patients to provide enough participants who could be assessed for feasibility of abdominal administration.
    30 Mar 2020
    No changes impacted study conduct.
    28 Aug 2020
    A randomized control arm comprising of patients treated with atezolizumab IV as per standard of care was added in Part 2. Investigational treatment in Part 2 was modified to atezolizumab monotherapy and inclusion criteria modified to include patients in whom platinum therapy had failed, to allow for assessment of atezolizumab SC without confounding factors associated with use in combination with chemotherapy.
    10 Feb 2021
    Subcutaneous site of first drug administration for Cohort 3 was changed from thigh to abdomen to accommodate patient convenience, increased patient privacy, and possible administration of higher drug volume. Study drug dosage for Cohort 3 was changed from 2400 mg Q4W to 1800 mg Q3W to assess the alternate administration site (abdomen). Enrollment for Cohort 3 was increased to approximately 20-30 patients to provide enough patients who could be assessed for feasibility of abdominal administration.
    25 Feb 2022
    Amendment 1: 1. Adverse event management guidelines have been updated to align with the atezolizumab investigator’s brochure, version 18. 2. References to an extended recruitment in China have been removed. 3. Estimand language in Section 6.6.2 has been 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 has been added. 5. Medical term “primary biliary cirrhosis” has been replaced by the term “primary biliary cholangitis” to align with the updated preferred term in MedDRA. 6. Responsibilities of the Principal Investigator and the role of the medical monitor in determining patient eligibility have been clarified. 7. Other minor changes.
    07 Feb 2023
    The medical term “Wegener granulomatosis” has been replaced by the term “granulomatosis with polyangiitis” to align with the updated preferred term in MedDRA. • The list of identified risks for atezolizumab has been revised to include pericardial disorders. • The list of identified risks for atezolizumab has been revised to include myelitis and facial paresis. • Hemophagocytic lymphohistiocytosis has been updated from a potential risk to an identified risk associated with atezolizumab and language has been revised accordingly. • The list of adverse events of special interest has been revised to include myelitis and facial paresis. • A description of the technical and organizational security measures taken to protect personal data has been added to align with CTR requirements. • Appendix 8 has been 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. • Appendix 8 has been revised to include autoimmune myelitis. • The adverse event management guidelines have been updated to align with the Addendum 1 and the Addendum 2 to the Atezolizumab Investigator’s Brochure, Version 19.

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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