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    Clinical Trial Results:
    A Phase III, Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Atezolizumab Given in Combination With Cabozantinib Versus Docetaxel Monotherapy in Patients With Metastatic Non-Small Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy

    Summary
    EudraCT number
    		 2020-000100-11
    Trial protocol
    		 DE   PT   BE   GB   GR   PL   FR   IT  
    Global end of trial date
    17 Jan 2025

    Results information
    Results version number
    		 v3(current)
    This version publication date
    20 Nov 2025
    First version publication date
    14 Oct 2023
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    GO41892
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04471428
    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, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Jan 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jan 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study is to evaluate the efficacy of atezolizumab in combination with cabozantinib (Atezo + Cabo) compared with docetaxel monotherapy in participants with metastatic non-small cell lung cancer (NSCLC), with no sensitizing endothelial growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation, who have progressed on prior treatment with both anti-programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibody and platinum-containing chemotherapy.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Oct 2020
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 44 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    Austria: 5
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Germany: 23
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    France: 27
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    Greece: 31
    Country: Number of subjects enrolled
    Italy: 45
    Country: Number of subjects enrolled
    Japan: 23
    Country: Number of subjects enrolled
    Korea, Republic of: 61
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Portugal: 16
    Country: Number of subjects enrolled
    Russian Federation: 24
    Country: Number of subjects enrolled
    United States: 29
    Worldwide total number of subjects
    366
    EEA total number of subjects
    210
    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)
    178
    From 65 to 84 years
    187
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 366 participants with metastatic NSCLC previously treated with anti-PD-L1/PD-1 antibody and platinum-containing chemotherapy took part in the study at 97 investigative sites across 15 countries from 01 October 2020 to 17 January 2025.

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1 ratio to receive either docetaxel monotherapy or atezolizumab & cabozantinib combination therapy. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Docetaxel Monotherapy
    Arm description
    		 Participants received docetaxel, 75 milligrams per square meter (mg/m^2), intravenously (IV) on Day 1 of each 21-day cycle until unacceptable toxicity or disease progression (PD) or loss of clinical benefit as determined by the investigator.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    RO0647746
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel, 75 mg/m^2, IV on Day 1 of each 21-day cycle.

    Arm title
    		 Atezolizumab + Cabozantinib
    Arm description
    		 Participants received atezolizumab, 1200 milligrams (mg), IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given once a day (QD) on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cabozantinib
    Investigational medicinal product code
    RO7047650
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cabozantinib, 40 mg, orally, QD, on Days 1-21 of each cycle (Cycle= 21 days)

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    RO5541267
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle

    Number of subjects in period 1
    		Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Started
    180
    186
    Safety-evaluable Population
    167
    185
    Completed
    0
    0
    Not completed
    180
    186
         Physician decision
    -
    1
         Death
    131
    147
         Reason Not Specified
    -
    2
         Withdrawal by Subject
    29
    4
         Study Terminated by Sponsor
    20
    29
         Lost to follow-up
    -
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Docetaxel Monotherapy
    Reporting group description
    		 Participants received docetaxel, 75 milligrams per square meter (mg/m^2), intravenously (IV) on Day 1 of each 21-day cycle until unacceptable toxicity or disease progression (PD) or loss of clinical benefit as determined by the investigator.

    Reporting group title
    Atezolizumab + Cabozantinib
    Reporting group description
    		 Participants received atezolizumab, 1200 milligrams (mg), IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given once a day (QD) on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.

    Reporting group values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib Total
    Number of subjects
    		 180 186 366
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 83 95 178
        From 65-84 years
    		 96 91 187
        85 years and over
    		 1 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.4 ( 9.4 ) 63.8 ( 9.5 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 53 52 105
        Male
    		 127 134 261
    Race (NIH/OMB)
    Units: Subjects
        Asian
    		 53 41 94
        Black or African American
    		 1 2 3
        White
    		 111 130 241
        Unknown or Not Reported
    		 15 13 28
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 7 4 11
        Not Hispanic or Latino
    		 158 164 322
        Not Stated
    		 12 15 27
        Unknown
    		 3 3 6

    End points

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    End points reporting groups
    Reporting group title
    Docetaxel Monotherapy
    Reporting group description
    		 Participants received docetaxel, 75 milligrams per square meter (mg/m^2), intravenously (IV) on Day 1 of each 21-day cycle until unacceptable toxicity or disease progression (PD) or loss of clinical benefit as determined by the investigator.

    Reporting group title
    Atezolizumab + Cabozantinib
    Reporting group description
    		 Participants received atezolizumab, 1200 milligrams (mg), IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given once a day (QD) on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. The intent-to-treat (ITT) population included all randomized participants, whether or not the participant received the assigned treatment.
    End point type
    Primary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: months
        median (confidence interval 95%)
    10.5 (8.6 to 13.0)
    10.7 (8.8 to 12.3)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Atezolizumab + Cabozantinib v Docetaxel Monotherapy
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.3668
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.884
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.676
         upper limit
    		 1.156
    Notes
    [1] - Stratification factors include histology, and prior NSCLC treatment regimens
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4709
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.907
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.696
         upper limit
    		 1.182

    Secondary: Progression-Free Survival (PFS) as Determined by Investigator

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    End point title
    		 Progression-Free Survival (PFS) as Determined by Investigator
    End point description
    PFS=time from randomization to first occurrence of PD, as determined by the investigator per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1), or death from any cause (whichever occurred first). PD= ≥ 20% increase in sum of longest diameters of target lesions, taking as reference smallest sum of longest diameters of target lesions recorded since treatment started, including screening, or appearance of one or more new lesions. In addition, sum of diameters also demonstrated an absolute increase of ≥ 5 millimeters (mm). Participants who were alive and did not experience PD at the time of analysis, were censored on the date of last tumor assessment. Participants with no post-baseline tumor assessment were censored at the date of randomization. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. ITT population=participants, whether or not the participant received the assigned treatment.
    End point type
    Secondary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: months
        median (confidence interval 95%)
    4.0 (3.1 to 4.4)
    4.6 (4.1 to 5.6)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0061
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.731
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.583
         upper limit
    		 0.915
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.0079
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.735
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.585
         upper limit
    		 0.923
    Notes
    [2] - Stratification factors include histology, and prior NSCLC treatment regimens

    Secondary: Confirmed Objective Response Rate (ORR) as Determined by Investigator

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    End point title
    		 Confirmed Objective Response Rate (ORR) as Determined by Investigator
    End point description
    Confirmed ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm. PR= at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. 95% CIs for rates were constructed using the Clopper-Pearson method. Percentages have been rounded off. ITT population included all randomized participants, whether or not the participant received the assigned treatment.
    End point type
    Secondary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: percentage of participants
        number (confidence interval 95%)
    13.3 (8.73 to 19.19)
    11.8 (7.56 to 17.36)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.6846
    Method
    		 Chi-square with Schouten Correction
    Parameter type
    		 Difference in Response Rates
    Point estimate
    -1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.85
         upper limit
    		 5.84
    Notes
    [3] - Stratification factors: histology, prior NSCLC treatment regimens
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7216
    Method
    		 Chi-squared corrected
    Parameter type
    		 Difference in Response Rates
    Point estimate
    -1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.85
         upper limit
    		 5.84
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.62
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.63
    Notes
    [4] - Stratification factors: histology, prior NSCLC treatment regimens

    Secondary: Duration of response (DOR) as Determined by Investigator

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    End point title
    		 Duration of response (DOR) as Determined by Investigator
    End point description
    DOR for participants with confirmed ORR=time from first documented OR to PD, or death, as per investigator per RECIST v1.1 (whichever occurred first). PD=≥ 20% increase in sum of longest diameters (SOLD) of target lesions (TL), taking as reference smallest SOLD of TL recorded since treatment started, including screening/ appearance of new lesions. In addition, sum of diameters (SOD) also demonstrated absolute increase of ≥ 5 mm. Confirmed ORR=percentage of participants with CR/PR on 2 consecutive occasions ≥4 weeks apart, as per investigator per RECIST v1.1. CR=disappearance of all TL. PR=≥ 30% decrease in SOD of all TL. Participants who had not progressed & who did not die at the time of analysis were censored at the time of last tumor assessment date. Kaplan-Meier method was used to estimate median. 95% CI for median was computed using Brookmeyer & Crowley method. ITT population=participants with confirmed objective response (CR/PR) as per the investigator per RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    24
    22
    Units: months
        median (confidence interval 95%)
    4.30 (3.29 to 5.62)
    5.55 (3.12 to 10.25)
    No statistical analyses for this end point

    Secondary: Time to Confirmed Deterioration (TTCD) in Patient-reported Physical Functioning (PF)

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    End point title
    		 Time to Confirmed Deterioration (TTCD) in Patient-reported Physical Functioning (PF)
    End point description
    TTCD, performed for patient-reported PF (items 1 to 5) of European Organisation for Research & Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30), was measured on 4-point scale (1=Not at all to 4=Very much). TTCD for PF=time from randomization to first confirmed clinically meaningful decrease (CMD) from baseline in PF score held for ≥2 consecutive assessments/initial CMD (≥10 points) from baseline followed by death from any cause within 21 days or until next tumor assessment, whichever occurs first. Scores were averaged, transformed to 0-100 scale; where higher score represented high/healthy level of functioning. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using Brookmeyer and Crowley method. ITT population=all randomized participants, whether or not the participant received the assigned treatment. 9999=upper limit of 95% confidence interval (CI) was not estimable due to insufficient events after the median estimate.
    End point type
    Secondary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: months
        median (confidence interval 95%)
    5.6 (4.0 to 9999)
    7.7 (4.8 to 14.7)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.27
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.16
    Notes
    [5] - Stratification factors include histology, and prior NSCLC treatment regimens
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3031
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.17

    Secondary: TTCD in Patient-Reported Global Health Status (GHS)

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    End point title
    		 TTCD in Patient-Reported Global Health Status (GHS)
    End point description
    TTCD, performed for GHS and quality of life (QoL) (items 29 and 30) of EORTC QLQ-C30, was measured on 7-point scale (very poor to excellent). TTCD for GHS/QoL=time from randomization to first confirmed CMD from baseline in GHS/QoL score held for ≥2 consecutive assessments/initial CMD (≥10 points) from baseline followed by death from any cause within 21 days or until next tumor assessment, whichever occurs first. Scores were averaged, transformed to 0-100 scale; where higher score represented better health-related QoL. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using Brookmeyer and Crowley method. ITT population=all randomized participants, whether or not the participant received the assigned treatment. 9999=upper limit of 95% CI was not estimable due to insufficient events after the median estimate.
    End point type
    Secondary
    End point timeframe
    Up to approximately 24 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: months
        median (confidence interval 95%)
    14.1 (6.3 to 9999)
    8.1 (5.6 to 14.5)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1992
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.81
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.2408
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.79
    Notes
    [6] - Stratification factors include histology, and prior NSCLC treatment regimens

    Secondary: PFS Rates Assessed by Investigator

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    End point title
    		 PFS Rates Assessed by Investigator
    End point description
    PFS rates were defined as the percentage of participants alive and without PD as assessed by the investigator according to RECIST v1.1 at 6 months and 1 year after randomization. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints, including baseline. In addition, the sum of diameters also demonstrated an absolute increase of ≥ 5 mm. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. Percentages have been rounded off. ITT population included all randomized participants, whether or not the participant received the assigned treatment.
    End point type
    Secondary
    End point timeframe
    6 months and 1 year
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: percentage of participants
    number (confidence interval 95%)
        At 6 months
    23.66 (16.98 to 30.33)
    39.51 (32.42 to 46.59)
        At 1 year
    8.38 (3.95 to 12.80)
    14.70 (9.43 to 19.97)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    At 1 year
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0719
    Method
    		 z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    6.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.56
         upper limit
    		 13.21
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    At 6 months
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0014
    Method
    		 z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    15.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.12
         upper limit
    		 25.59

    Secondary: OS Rates

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    End point title
    		 OS Rates
    End point description
    OS rates were defined as the percentage of participants who were alive at 1 and 2 years. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. Percentages have been rounded off. ITT population is defined as all randomized participants, whether or not the participant received the assigned treatment. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. At the time of the analysis, there were no participants with 24 months or more of survival follow-up, therefore, survival rate at the 2-year timepoint was not estimable. 99999=survival rate at the 2-year time point was not estimable as there were no participants with 24 months or more of survival follow-up.
    End point type
    Secondary
    End point timeframe
    1 and 2 years
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    180
    186
    Units: percentage of participants
    number (confidence interval 95%)
        1 year
    44.12 (36.20 to 52.05)
    43.27 (35.97 to 50.57)
        2 years
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    		 Docetaxel, Atezolizumab + Cabozantinib
    Statistical analysis description
    At 1 year
    Comparison groups
    Docetaxel Monotherapy v Atezolizumab + Cabozantinib
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8767
    Method
    		 z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.63
         upper limit
    		 9.92

    Secondary: Percentage of Participants With Adverse Events (AEs)

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    End point title
    		 Percentage of Participants With Adverse Events (AEs)
    End point description
    An AE was defined as any untoward medical occurrence in a clinical investigation patient administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition not present at baseline; any deterioration in a laboratory value or other clinical test; AEs related to a protocol-mandated intervention. AEs were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v5.0). Percentages have been rounded off. Safety-evaluable population=all randomized participants who had received any amount of study drug, with participants grouped according to the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Up to approximately 41.4 months
    End point values
    		 Docetaxel Monotherapy Atezolizumab + Cabozantinib
    Number of subjects analysed
    167
    185
    Units: percentage of participants
        number (not applicable)
    94.0
    98.4
    No statistical analyses for this end point

    Secondary: Minimum Serum Concentration (Cmin) of Atezolizumab

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    End point title
    		 Minimum Serum Concentration (Cmin) of Atezolizumab [7]
    End point description
    Pharmacokinetic (PK)-evaluable population for atezolizumab included all participants who had received any dose of atezolizumab and who had evaluable PK samples. Number analyzed is the number of participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint. 9999= the data was not evaluable as all samples were below limit of quantitation (BLQ).
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1, 2, 3, 4, 8, 12 and 16 (Cycle=21 days)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    		 Atezolizumab + Cabozantinib
    Number of subjects analysed
    185
    Units: microgram/milliliter (μg/ml)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 (n=146)
    9999 ( 9999 )
        Cycle 2 Day 1 (n=162)
    96.8 ( 48.1 )
        Cycle 3 Day 1 (n=140)
    124 ( 104.4 )
        Cycle 4 Day 1 (n=130)
    167 ( 47.7 )
        Cycle 8 Day 1 (n=70)
    194 ( 62.4 )
        Cycle 12 Day 1 (n=52)
    233 ( 44.7 )
        Cycle 16 Day 1 (n=40)
    209 ( 56.1 )
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of Atezolizumab

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    End point title
    		 Maximum Serum Concentration (Cmax) of Atezolizumab [8]
    End point description
    PK-evaluable population included all participants who had received any dose of atezolizumab and who had evaluable PK samples.
    End point type
    Secondary
    End point timeframe
    30 min postdose on Day 1 of Cycle 1 (Cycle=21 days)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    		 Atezolizumab + Cabozantinib
    Number of subjects analysed
    185
    Units: μg/ml
        geometric mean (geometric coefficient of variation)
    450 ( 34.0 )
    No statistical analyses for this end point

    Secondary: Minimum Plasma Concentration (Cmin) of Cabozantinib

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    End point title
    		 Minimum Plasma Concentration (Cmin) of Cabozantinib [9]
    End point description
    PK-evaluable population included all participants who had received any dose of cabozantinib and who had evaluable PK samples. n=number of participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint. 9999= the data was not evaluable as all samples were BLQ.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    		 Atezolizumab + Cabozantinib
    Number of subjects analysed
    185
    Units: μg/ml
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 (n=173)
    9999 ( 9999 )
        Cycle 2 Day 1 (n=163)
    0.746 ( 111.7 )
        Cycle 3 Day 1 (n=138)
    0.418 ( 640.7 )
        Cycle 4 Day 1 (n=131)
    0.469 ( 234.4 )
        Cycle 5 Day 1 (n=110)
    0.303 ( 402.3 )
    No statistical analyses for this end point

    Secondary: Maximum Plasma Concentration (Cmax) of Cabozantinib

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    End point title
    		 Maximum Plasma Concentration (Cmax) of Cabozantinib [10]
    End point description
    Cmax was not collected for this outcome measure because PK of cabozantinib was well characterized through the cabozantinib development for mono- therapy. An established population PK model for cabozantinib is available for the PK data from NCT04471428 (study GO41892). The PK data collected in the current study is sufficient for the population PK model to characterize the exposure of cabozantinib in this study.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    		 Atezolizumab + Cabozantinib
    Number of subjects analysed
    0 [11]
    Units: μg/ml
        geometric mean (geometric coefficient of variation)
    ( )
    Notes
    [11] - Cabozantinib's PK was well studied through development of it's monotherapy, no need to measure Cmax.
    No statistical analyses for this end point

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

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    End point title
    		 Number of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [12]
    End point description
    Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). The total number of participants who developed ADAs to atezolizumab was determined by summing the ADA-positive participants across all timepoints. Safety-evaluable population included all randomized participants who had received any amount of study drug, with participants grouped according to the actual treatment received. Number analyzed is the number of participants with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1,2,3,4,8,12 and 16 (each cycle is 21 days) and at post-treatment follow-up visit (≤ 30 days after final dose)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    		 Atezolizumab + Cabozantinib
    Number of subjects analysed
    177
    Units: participants
        ADA Prevalence at Baseline (n=177)
    2
        ADA Incidence after treatment (n=173)
    37
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months
    Adverse event reporting additional description
    Safety-evaluable population included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Atezolizumab + Cabozantinib
    Reporting group description
    		 Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.

    Reporting group title
    Docetaxel Monotherapy
    Reporting group description
    		 Participants received docetaxel, 75 mg/m^2, IV on Day 1 of each 21-day cycle until unacceptable toxicity or PD or loss of clinical benefit as determined by the investigator.

    Serious adverse events
    		 Atezolizumab + Cabozantinib Docetaxel Monotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    76 / 185 (41.08%)
    58 / 167 (34.73%)
         number of deaths (all causes)
    149
    130
         number of deaths resulting from adverse events
    4
    1
    Vascular disorders
    Intermittent claudication
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 185 (1.62%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 185 (2.70%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    3 / 185 (1.62%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Condition aggravated
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 185 (0.00%)
    4 / 167 (2.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Dyspnoea
         subjects affected / exposed
    2 / 185 (1.08%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 185 (1.62%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    2 / 185 (1.08%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Bronchial fistula
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    3 / 185 (1.62%)
    5 / 167 (2.99%)
         occurrences causally related to treatment / all
    3 / 3
    4 / 5
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 185 (0.54%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Spinal fracture
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumopericardium
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    2 / 185 (1.08%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 185 (1.08%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 185 (0.00%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 185 (0.00%)
    8 / 167 (4.79%)
         occurrences causally related to treatment / all
    0 / 0
    9 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 185 (0.54%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal disorder
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal fistula
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 185 (2.16%)
    3 / 167 (1.80%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 185 (1.62%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 185 (1.62%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hidradenitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder disorder
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal insufficiency
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    10 / 185 (5.41%)
    10 / 167 (5.99%)
         occurrences causally related to treatment / all
    0 / 10
    4 / 10
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine infection
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 185 (1.08%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    4 / 185 (2.16%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory tract infection
         subjects affected / exposed
    1 / 185 (0.54%)
    2 / 167 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 185 (1.08%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial colitis
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mycobacterium avium complex infection
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 185 (0.00%)
    1 / 167 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cachexia
         subjects affected / exposed
    1 / 185 (0.54%)
    0 / 167 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Atezolizumab + Cabozantinib Docetaxel Monotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    173 / 185 (93.51%)
    148 / 167 (88.62%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    17 / 185 (9.19%)
    2 / 167 (1.20%)
         occurrences all number
    25
    3
    General disorders and administration site conditions
    Mucosal inflammation
         subjects affected / exposed
    11 / 185 (5.95%)
    9 / 167 (5.39%)
         occurrences all number
    17
    10
    Asthenia
         subjects affected / exposed
    43 / 185 (23.24%)
    40 / 167 (23.95%)
         occurrences all number
    53
    45
    Malaise
         subjects affected / exposed
    5 / 185 (2.70%)
    9 / 167 (5.39%)
         occurrences all number
    5
    9
    Fatigue
         subjects affected / exposed
    42 / 185 (22.70%)
    44 / 167 (26.35%)
         occurrences all number
    48
    48
    Pyrexia
         subjects affected / exposed
    20 / 185 (10.81%)
    12 / 167 (7.19%)
         occurrences all number
    21
    12
    Oedema peripheral
         subjects affected / exposed
    8 / 185 (4.32%)
    12 / 167 (7.19%)
         occurrences all number
    8
    15
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    27 / 185 (14.59%)
    25 / 167 (14.97%)
         occurrences all number
    29
    25
    Dysphonia
         subjects affected / exposed
    16 / 185 (8.65%)
    1 / 167 (0.60%)
         occurrences all number
    19
    1
    Cough
         subjects affected / exposed
    20 / 185 (10.81%)
    12 / 167 (7.19%)
         occurrences all number
    25
    14
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    17 / 185 (9.19%)
    7 / 167 (4.19%)
         occurrences all number
    18
    7
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    36 / 185 (19.46%)
    7 / 167 (4.19%)
         occurrences all number
    53
    7
    Aspartate aminotransferase increased
         subjects affected / exposed
    31 / 185 (16.76%)
    4 / 167 (2.40%)
         occurrences all number
    42
    4
    Platelet count decreased
         subjects affected / exposed
    15 / 185 (8.11%)
    0 / 167 (0.00%)
         occurrences all number
    27
    0
    Weight decreased
         subjects affected / exposed
    30 / 185 (16.22%)
    6 / 167 (3.59%)
         occurrences all number
    30
    7
    Neutrophil count decreased
         subjects affected / exposed
    8 / 185 (4.32%)
    12 / 167 (7.19%)
         occurrences all number
    17
    19
    Amylase increased
         subjects affected / exposed
    10 / 185 (5.41%)
    2 / 167 (1.20%)
         occurrences all number
    11
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    14 / 185 (7.57%)
    5 / 167 (2.99%)
         occurrences all number
    15
    5
    Neuropathy peripheral
         subjects affected / exposed
    4 / 185 (2.16%)
    9 / 167 (5.39%)
         occurrences all number
    4
    9
    Dysgeusia
         subjects affected / exposed
    20 / 185 (10.81%)
    10 / 167 (5.99%)
         occurrences all number
    24
    14
    Headache
         subjects affected / exposed
    14 / 185 (7.57%)
    14 / 167 (8.38%)
         occurrences all number
    16
    18
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    24 / 185 (12.97%)
    38 / 167 (22.75%)
         occurrences all number
    26
    47
    Thrombocytopenia
         subjects affected / exposed
    17 / 185 (9.19%)
    1 / 167 (0.60%)
         occurrences all number
    20
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    31 / 185 (16.76%)
    17 / 167 (10.18%)
         occurrences all number
    35
    17
    Nausea
         subjects affected / exposed
    47 / 185 (25.41%)
    29 / 167 (17.37%)
         occurrences all number
    56
    42
    Diarrhoea
         subjects affected / exposed
    83 / 185 (44.86%)
    38 / 167 (22.75%)
         occurrences all number
    134
    62
    Abdominal pain
         subjects affected / exposed
    21 / 185 (11.35%)
    5 / 167 (2.99%)
         occurrences all number
    27
    5
    Abdominal pain upper
         subjects affected / exposed
    11 / 185 (5.95%)
    2 / 167 (1.20%)
         occurrences all number
    12
    2
    Vomiting
         subjects affected / exposed
    29 / 185 (15.68%)
    11 / 167 (6.59%)
         occurrences all number
    36
    14
    Stomatitis
         subjects affected / exposed
    28 / 185 (15.14%)
    13 / 167 (7.78%)
         occurrences all number
    30
    14
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    4 / 185 (2.16%)
    40 / 167 (23.95%)
         occurrences all number
    4
    40
    Rash
         subjects affected / exposed
    17 / 185 (9.19%)
    13 / 167 (7.78%)
         occurrences all number
    20
    14
    Pruritus
         subjects affected / exposed
    15 / 185 (8.11%)
    6 / 167 (3.59%)
         occurrences all number
    19
    7
    Dry skin
         subjects affected / exposed
    11 / 185 (5.95%)
    7 / 167 (4.19%)
         occurrences all number
    11
    7
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    40 / 185 (21.62%)
    2 / 167 (1.20%)
         occurrences all number
    54
    2
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    22 / 185 (11.89%)
    3 / 167 (1.80%)
         occurrences all number
    30
    3
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    30 / 185 (16.22%)
    0 / 167 (0.00%)
         occurrences all number
    32
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    26 / 185 (14.05%)
    20 / 167 (11.98%)
         occurrences all number
    31
    23
    Pain in extremity
         subjects affected / exposed
    12 / 185 (6.49%)
    4 / 167 (2.40%)
         occurrences all number
    15
    4
    Back pain
         subjects affected / exposed
    18 / 185 (9.73%)
    7 / 167 (4.19%)
         occurrences all number
    20
    9
    Myalgia
         subjects affected / exposed
    11 / 185 (5.95%)
    19 / 167 (11.38%)
         occurrences all number
    14
    23
    Muscle spasms
         subjects affected / exposed
    11 / 185 (5.95%)
    3 / 167 (1.80%)
         occurrences all number
    13
    3
    Infections and infestations
    COVID-19
         subjects affected / exposed
    14 / 185 (7.57%)
    4 / 167 (2.40%)
         occurrences all number
    15
    4
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    12 / 185 (6.49%)
    10 / 167 (5.99%)
         occurrences all number
    17
    10
    Hypomagnesaemia
         subjects affected / exposed
    23 / 185 (12.43%)
    4 / 167 (2.40%)
         occurrences all number
    29
    5
    Hypoalbuminaemia
         subjects affected / exposed
    20 / 185 (10.81%)
    12 / 167 (7.19%)
         occurrences all number
    23
    16
    Hypocalcaemia
         subjects affected / exposed
    20 / 185 (10.81%)
    7 / 167 (4.19%)
         occurrences all number
    35
    7
    Decreased appetite
         subjects affected / exposed
    59 / 185 (31.89%)
    28 / 167 (16.77%)
         occurrences all number
    64
    31
    Hypokalaemia
         subjects affected / exposed
    15 / 185 (8.11%)
    8 / 167 (4.79%)
         occurrences all number
    15
    9
    Hypophosphataemia
         subjects affected / exposed
    12 / 185 (6.49%)
    5 / 167 (2.99%)
         occurrences all number
    13
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jun 2020
    - Exclusion criteria were added for severe hepatic impairment and known allergy or hypersensitivity to the cabozantinib formulation.
    18 Mar 2021
    - The exclusion criteria were amended to exclude participants with known repressor of silencing 1 (ROS1) rearrangements, or BRAF valine (V) substituted by glutamic acid (E) at amino acid 600 (BRAF V600E) mutations, or other actionable oncogenes with approved therapies if available; to clarify the timeline for prior ischemic events or significant cardiovascular disease; to clarify mineralocorticoid or corticosteroid use. -The use of direct acting oral anticoagulants was clarified in the exclusion criteria, permitted therapy, and management of thromboembolic events associated with cabozantinib. -The exclusion criteria were amended to exclude participants with arterial dissection and other significant vascular disease in order to align with cabozantinib Summary of Product Characteristics (SmPC) -Stratification factors for randomization were clarified to require PD before using a second-line agent, and to distinguish between platinum-containing chemotherapy given without anti-PD-L1/PD-1 antibody versus platinum-containing chemotherapy given in combination with anti-PD-L1/PD-1 antibody.
    10 Mar 2022
    - A benefit-risk assessment and guidance on concomitant administration of COVID-19 vaccines with atezolizumab were added. - Immune RECIST (iRECIST) appendix was removed to align with a program level decision to no longer perform exploratory analyses of response rate and progression-free survival according to iRECIST criteria.
    22 Mar 2023
    - Two newly approved indications for cabozantinib were added to align with the cabozantinib investigator’s brochure, version 18. - The completion of patient-reported outcome (PRO) questionnaires was no longer required after the final OS analysis. - The duration of follow-up after the completion of final OS analysis was specified as 6 months after patient’s last dose of study treatment. - The end-of-study definition was updated to include the additional criteria of when the last data point required for safety follow-up has been received (if it occurs later than the required number of deaths for the final analysis OS), and the last patient’s last visit (LPLV) has occurred. Participants may continue study treatment until the development of PD, unacceptable toxicity, patient consent withdrawal, or sponsor’s decision to terminate the study, whichever occurs first. The Sponsor will provide a written notification to investigators if the study has terminated and the investigators, in consultation with the medical monitor, may offer suitable participants with potential enrollment to the continued access program or another study for continued access to study treatment.

    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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