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    Clinical Trial Results:
    A phase III randomized, double-blinded trial of platinum-based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal or peritoneal cancer and platinum treatment-free interval (TFIp) >6 months.

    Summary
    EudraCT number
    		 2018-000366-11
    Trial protocol
    		 ES   FR   DE   BE   IT  
    Global end of trial date
    04 Mar 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jun 2025
    First version publication date
    14 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ENGOT-Ov41/GEICO69-O/ANITA
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03598270
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Grupo Español de Investigación en Cáncer Ginecologico (GEICO)
    Sponsor organisation address
    Santa Engracia, 151, 5th floor, 2nd door.;, Madrid, Spain, 28003
    Public contact
    Iratxe Puebla, Grupo Español de Investigación en Cáncer Ginecologico (GEICO), ipuebla@grupogeico.net
    Scientific contact
    Iratxe Puebla, Grupo Español de Investigación en Cáncer Ginecologico (GEICO), ipuebla@grupogeico.net
    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
    04 Mar 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Mar 2025
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Mar 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Determine whether the addition of atezolizumab to carboplatin-based chemotherapy followed by maintenance niraparib improves progression-free survival (PFS) compared to placebo combined with carboplatin-based chemotherapy followed by maintenance niraparib, in patients with relapsed epithelial ovarian, fallopian tube, or peritoneal cancer after a platinum treatment free interval (TFIp) of at least 6 months (platinum-sensitive).
    Protection of trial subjects
    The patient signed the informed consent before carrying out any procedure related to the study. Physical examination, vital signs, 12-lead ECG, hematology, biochemistry, urinalysis, pregnancy test if applicable and tumor evaluation were made before to start study treatment and during their participation in the study, according to the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Nov 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
    Israel: 3
    Country: Number of subjects enrolled
    Spain: 222
    Country: Number of subjects enrolled
    Belgium: 33
    Country: Number of subjects enrolled
    France: 89
    Country: Number of subjects enrolled
    Germany: 36
    Country: Number of subjects enrolled
    Italy: 34
    Worldwide total number of subjects
    417
    EEA total number of subjects
    414
    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)
    233
    From 65 to 84 years
    183
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 417 patients were recruited during the study

    Pre-assignment
    Screening details
    		 Of the 548 patients that signed the ICF, 131 were screening failures and 417 started treatment in the trial. 131 patients were screening failures, most of them because they did not meet the eligibility criteria of the trial.

    Period 1
    Period 1 title
    Global (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A (control arm)
    Arm description
    		 Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with placebo q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo of atezolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1- Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. 2- Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. 3- Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1- Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. 2- Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. 3- Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk.

    Investigational medicinal product name
    Pegylated liposomal doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.

    Arm title
    		 ARM B (experimental arm)
    Arm description
    		 Atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with atezolizumab q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1- Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk. 2- Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk. 3- Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1- Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk. 2- Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk. 3- Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk.

    Investigational medicinal product name
    Pegylated liposomal doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.

    Number of subjects in period 1
    		ARM A (control arm) ARM B (experimental arm)
    Started
    209
    208
    Completed
    209
    208

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ARM A (control arm)
    Reporting group description
    		 Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with placebo q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.

    Reporting group title
    ARM B (experimental arm)
    Reporting group description
    		 Atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with atezolizumab q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.

    Reporting group values
    		 ARM A (control arm) ARM B (experimental arm) Total
    Number of subjects
    		 209 208 417
    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)
    		 120 113 233
        From 65-84 years
    		 89 94 183
        85 years and over
    		 0 1 1
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 62 (56 to 69) 63 (55 to 70) -
    Gender categorical
    Units: Subjects
        Female
    		 209 208 417
    Screening visit 1 ECOG/PS
    Units: Subjects
        ECOG 0
    		 128 134 262
        ECOG 1
    		 81 74 155
    Histologic diagnosis
    Units: Subjects
        High Grade Serous Ovarian Cancer
    		 196 187 383
        High Grade Endometroid Ovarian Cancer
    		 5 11 16
        Mixed histology
    		 5 7 12
        Undifferentiated
    		 3 3 6
    Origin
    Units: Subjects
        Ovarian
    		 188 189 377
        Tubal carcinoma
    		 15 10 25
        Primary peritoneal
    		 6 9 15
    BRCA status
    Units: Subjects
        Not-Mutated
    		 178 181 359
        Mutated
    		 31 27 58
    Number of previous anticancer treatment lines
    Units: Subjects
        1 Line
    		 181 181 362
        2 Lines
    		 28 27 55
    Previous treatment with Bevacizumab
    Units: Subjects
        No
    		 98 89 187
        Yes
    		 111 119 230
    Previous treatment with PARPi
    Units: Subjects
        No
    		 182 188 370
        Yes
    		 27 20 47
    Time from last dose of platinum to progression
    Units: Subjects
        6-12 months
    		 70 73 143
        >12 months
    		 139 135 274
    1st line: Primary debulking surgery?
    Units: Subjects
        No
    		 93 90 183
        Yes
    		 116 118 234
    1st line: Primary debulking surgery result
    Units: Subjects
        Optimal
    		 73 82 155
        Suboptimal
    		 29 18 47
        Unknown
    		 14 18 32
        Not applicable
    		 93 90 183
    1st line: Interval debulking surgery (IDS) done?
    Units: Subjects
        No
    		 128 131 259
        Yes
    		 81 77 158
    1st line: IDS result
    Units: Subjects
        Optimal
    		 56 51 107
        Suboptimal
    		 19 18 37
        Unknown
    		 5 8 13
        Not applicable
    		 129 131 260
    1st line: Treatment with antiangiogenic agent in a clinical trial
    Units: Subjects
        No
    		 175 164 339
        Yes
    		 34 44 78
    1st line: Treatment with PARPi inhibitor in a clinical trial
    Units: Subjects
        No
    		 185 194 379
        Yes
    		 24 14 38
    2nd line: Primary debulking surgery?
    Units: Subjects
        No
    		 16 17 33
        Yes
    		 11 10 21
        Not applicable
    		 182 181 363
    2nd line: Primary debulking surgery result
    Units: Subjects
        Optimal
    		 8 8 16
        Suboptimal
    		 3 2 5
        Not applicable
    		 198 198 396
    2nd line: Secondary debulking surgery after some cycles of chemotherapy
    Units: Subjects
        No
    		 26 25 51
        Yes
    		 1 2 3
        Not applicable
    		 182 181 363
    2nd line: Treatment with antiangiogenic agent in a clinical trial
    Units: Subjects
        No
    		 25 22 47
        Yes
    		 3 5 8
        Not applicable
    		 181 181 362
    2nd line: Treatment with PARPi inhibitor in a clinical trial
    Units: Subjects
        No
    		 27 27 54
        Yes
    		 1 0 1
        Not applicable
    		 181 181 362
    Number of affected locations per patient
    Units: Subjects
        1 lesion
    		 35 39 74
        2 lesions
    		 73 65 138
        3 lesions
    		 51 47 98
        4 lesions
    		 34 28 62
        5 lesions
    		 11 22 33
        6 lesions
    		 2 6 8
        7 lesions
    		 2 1 3
        8 lesions
    		 1 0 1
    Treatment Regimen
    Units: Subjects
        Regimen 1
    		 25 29 54
        Regimen 2
    		 33 32 65
        Regimen 3
    		 151 147 298

    End points

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    End points reporting groups
    Reporting group title
    ARM A (control arm)
    Reporting group description
    		 Placebo of atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with placebo q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and placebo (volume equivalent to 1200 mg of atezolizumab drug product, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and placebo (volume equivalent to 840 mg of atezolizumab drug product, d1 & d15) IV q4 wk.

    Reporting group title
    ARM B (experimental arm)
    Reporting group description
    		 Atezolizumab in combination with one of the platinum based regimens below (investigator’s choice) followed by maintenance niraparib with atezolizumab q3 wk: •Carboplatin (AUC = 5, d1) combined with paclitaxel (175 mg/m², d1) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) and atezolizumab (1200 mg, d1) IV q3 wk. •Carboplatin (AUC = 5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) and atezolizumab (840 mg, d1& d15) IV q4 wk.

    Primary: Progression-free survival (PFS)

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    End point title
    		 Progression-free survival (PFS)
    End point description
    The primary endpoint of the study is progression-free survival (PFS) from randomization until progression based on investigator assessment determined by RECIST (version v1.1).
    End point type
    Primary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
        median (confidence interval 95%)
    9.901 (9.243 to 11.09)
    10.63 (9.901 to 11.78)
    Statistical analysis title
    		 PFS
    Comparison groups
    ARM A (control arm) v ARM B (experimental arm)
    Number of subjects included in analysis
    417
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.929
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.757
         upper limit
    		 1.139

    Secondary: Overall survival (OS)

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    End point title
    		 Overall survival (OS)
    End point description
    Overall survival (OS), defined as the observed length of life from entry into the study (day of randomization) to death from any cause, or the date of last contact
    End point type
    Secondary
    End point timeframe
    Every study visit until a maximun of 66 months
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
        median (confidence interval 95%)
    27.11 (23.22 to 32.34)
    32.17 (27.14 to 34.80)
    No statistical analyses for this end point

    Secondary: Time from randomization to first subsequent therapy or death (TFST)

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    End point title
    		 Time from randomization to first subsequent therapy or death (TFST)
    End point description
    Time from randomization to first subsequent therapy or death (TFST)
    End point type
    Secondary
    End point timeframe
    Every 12 weeks until end of study, withdrawal of consent or the patient is lost to follow up. Maximun 66 months
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
        median (confidence interval 95%)
    13.45 (12.11 to 13.95)
    12.89 (11.78 to 14.77)
    No statistical analyses for this end point

    Secondary: Time from randomization to second subsequent therapy or death (TSST)

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    End point title
    		 Time from randomization to second subsequent therapy or death (TSST)
    End point description
    Time from randomization to second subsequent therapy or death (TSST)
    End point type
    Secondary
    End point timeframe
    Every 12 weeks until end of study, withdrawal of consent or the patient is lost to follow up. Maximun 66 months
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
        median (confidence interval 95%)
    19.51 (17.43 to 22.37)
    20.03 (17.99 to 21.91)
    No statistical analyses for this end point

    Secondary: Time from randomization to second progression or death (PFS2)

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    End point title
    		 Time from randomization to second progression or death (PFS2)
    End point description
    Time from randomization to second progression or death (PFS2)
    End point type
    Secondary
    End point timeframe
    Every 12 weeks until end of study, withdrawal of consent or the patient is lost to follow up. Maximun 66 months
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
        median (confidence interval 95%)
    18.39 (16.71 to 20.59)
    19.70 (17.30 to 20.59)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) during the chemotherapy phase

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    End point title
    		 Objective Response Rate (ORR) during the chemotherapy phase
    End point description
    Objective Response Rate (ORR) as assessed by RECIST v1.1 during the chemotherapy phase (complete and partial responses)
    End point type
    Secondary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: Percentage
        median (confidence interval 95%)
    43.06 (36.35 to 49.78)
    46.63 (39.85 to 53.41)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) during maintenance

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    End point title
    		 Overall Response Rate (ORR) during maintenance
    End point description
    Objective Response Rate (ORR) as assessed by RECIST v1.1 during the maintenance phase (complete and partial responses).
    End point type
    Secondary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    158
    156
    Units: percentage
        median (confidence interval 95%)
    28.5 (21.4 to 35.5)
    41.0 (33.3 to 48.7)
    No statistical analyses for this end point

    Secondary: Duration of response (DOR)

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    End point title
    		 Duration of response (DOR)
    End point description
    Duration of response (DOR) by RECIST v1.1
    End point type
    Secondary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    101
    120
    Units: months
        median (confidence interval 95%)
    9.243 (7.895 to 11.12)
    10.66 (9.211 to 12.43)
    No statistical analyses for this end point

    Secondary: PFS by treatment arm and BRCA

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    End point title
    		 PFS by treatment arm and BRCA
    End point description
    PFS by treatment arm and BRCA
    End point type
    Secondary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    209
    208
    Units: months
    median (confidence interval 95%)
        Mutated
    11.94 (9.803 to 26.97)
    12.70 (8.322 to 16.84)
        Not-Mutated
    9.704 (8.816 to 10.49)
    10.59 (9.572 to 11.55)
    No statistical analyses for this end point

    Secondary: PFS by treatment arm and PDL1 status

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    End point title
    		 PFS by treatment arm and PDL1 status
    End point description
    PFS by treatment arm and PDL1 status
    End point type
    Secondary
    End point timeframe
    Every 9 weeks during the chemotherapy phase and every 12 weeks during the maintenance phase until progression up to a maximum of 64 months.
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    206
    207
    Units: months
    median (confidence interval 95%)
        PD-L1 Negative
    9.24 (8.32 to 11.09)
    10.36 (9.01 to 11.32)
        PD-L1 Positive
    10.49 (9.34 to 12.17)
    12.53 (10.20 to 14.80)
        PD-L1 Non-informative
    9.44 (6.51 to 12.99)
    9.77 (2.76 to 11.78)
    No statistical analyses for this end point

    Secondary: Abdominal/GI symptom change from baseline to latest evaluation available (EORTC QLQ-OV28)

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    End point title
    		 Abdominal/GI symptom change from baseline to latest evaluation available (EORTC QLQ-OV28)
    End point description
    Clinically-meaningful improvement in patient-reported abdominal pain or bloating, defined as a 10-point decrease from the baseline score on either of the two items of the EORTC QLQ-OV28 abdominal/GI symptom scale (items 31 and 32)
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    183
    168
    Units: percentage
        arithmetic mean (standard deviation)
    1.4 ( 20.3 )
    2.8 ( 20.6 )
    No statistical analyses for this end point

    Secondary: QLQ-OV28: Abdominal/GI symptom change from baseline to latest evaluation available (Clinical improvement/Deterioration)

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    End point title
    		 QLQ-OV28: Abdominal/GI symptom change from baseline to latest evaluation available (Clinical improvement/Deterioration)
    End point description
    Clinically-meaningful improvement in patient-reported abdominal pain or bloating, defined as a 10-point decrease from the baseline score on either of the two items of the EORTC QLQ-OV28 abdominal/GI symptom scale (items 31 and 32)
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    183
    168
    Units: patients
        Clinical improvement
    52
    45
        Remaining stable
    71
    66
        Deterioration
    60
    57
    No statistical analyses for this end point

    Secondary: QLQ-C30: Global health status changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: Global health status changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    185
    179
    Units: subjects
        Clinical improvement
    45
    26
        Remaining stable
    86
    79
        Deterioration
    54
    74
    No statistical analyses for this end point

    Secondary: QLQ-C30: role functioning changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: role functioning changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    188
    179
    Units: subjects
        Clinical improvement
    21
    17
        Remaining stable
    128
    113
        Deterioration
    39
    49
    No statistical analyses for this end point

    Secondary: QLQ-C30: Emotional functioning changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: Emotional functioning changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    182
    175
    Units: subjects
        Clinical improvement
    28
    20
        Remaining stable
    123
    126
        Deterioration
    31
    29
    No statistical analyses for this end point

    Secondary: QLQ-C30: Cognitive functioning changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: Cognitive functioning changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    182
    177
    Units: subjects
        Clinical improvement
    15
    4
        Remaining stable
    141
    148
        Deterioration
    26
    25
    No statistical analyses for this end point

    Secondary: QLQ-C30: Social functioning changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: Social functioning changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    182
    170
    Units: subjects
        Clinical improvement
    24
    17
        Remaining stable
    121
    107
        Deterioration
    37
    46
    No statistical analyses for this end point

    Secondary: QLQ-C30: Physical functioning changes from baseline to latest evaluation available

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    End point title
    		 QLQ-C30: Physical functioning changes from baseline to latest evaluation available
    End point description
    Clinical improvement, remaining stable, or deterioration in patient-reported function and HRQoL, defined as a 10-point increase, changes within 10 points, and a 10-point decrease, respectively, from the baseline score on each of the functional (physical, role, emotional, and social) and global health status/HRQoL scales of EORTC QLQ-C30
    End point type
    Secondary
    End point timeframe
    Every study visit during chemotherapy phase and then every 12 weeks until PFS2 or a maximum of 4 years
    End point values
    		 ARM A (control arm) ARM B (experimental arm)
    Number of subjects analysed
    184
    169
    Units: subjects
        Clinical improvement
    17
    15
        Remaining stable
    134
    123
        Deterioration
    33
    31
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The safety profile of patients will be monitored throughout the treatment and up to 30 days after the last treatment infusion. SAEs and AESIs until 90 days after the last dose of atezolizumab/placebo or until initiation of new systemic anti-cancer therapy
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    ARM A (control arm)
    Reporting group description
    		 ARM A (control arm): Placebo of atezolizumab in combination with one of the platinum based regimens (investigator’s choice) followed by maintenance niraparib with placebo:

    Reporting group title
    ARM B (experimental arm)
    Reporting group description
    		 ARM B (experimental arm): Atezolizumab in combination with one of the platinum based regimens (investigator’s choice) followed by maintenance niraparib with atezolizumab:

    Serious adverse events
    		 ARM A (control arm) ARM B (experimental arm)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    63 / 209 (30.14%)
    80 / 208 (38.46%)
         number of deaths (all causes)
    133
    125
         number of deaths resulting from adverse events
    4
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Breast cancer
         subjects affected / exposed
    2 / 209 (0.96%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lentigo maligna
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraneoplastic encephalomyelitis
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Undifferentiated nasopharyngeal carcinoma
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    2 / 209 (0.96%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 209 (0.48%)
    3 / 208 (1.44%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 209 (0.00%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchopneumopathy
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 209 (0.96%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 209 (0.48%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 209 (0.48%)
    3 / 208 (1.44%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 209 (0.00%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated encephalitis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 209 (0.48%)
    4 / 208 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    4 / 209 (1.91%)
    13 / 208 (6.25%)
         occurrences causally related to treatment / all
    5 / 5
    10 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune thrombocytopenia
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 209 (0.96%)
    7 / 208 (3.37%)
         occurrences causally related to treatment / all
    2 / 2
    10 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 209 (0.96%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    13 / 209 (6.22%)
    6 / 208 (2.88%)
         occurrences causally related to treatment / all
    15 / 16
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 209 (1.44%)
    4 / 208 (1.92%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 209 (0.96%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal obstruction
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    7 / 209 (3.35%)
    6 / 208 (2.88%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    2 / 209 (0.96%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 209 (0.00%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 209 (0.96%)
    4 / 208 (1.92%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 209 (0.48%)
    4 / 208 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cytolysis
         subjects affected / exposed
    0 / 209 (0.00%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (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
    Skin toxicity
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Vitiligo
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 209 (0.48%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal disorder
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial diarrhoea
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 209 (0.96%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    2 / 209 (0.96%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected lymphocele
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 209 (1.44%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 209 (0.00%)
    3 / 208 (1.44%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    Stoma site infection
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 209 (0.00%)
    2 / 208 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Food intolerance
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 209 (0.48%)
    1 / 208 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 ARM A (control arm) ARM B (experimental arm)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    206 / 209 (98.56%)
    207 / 208 (99.52%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    22 / 209 (10.53%)
    34 / 208 (16.35%)
         occurrences all number
    30
    49
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    126 / 209 (60.29%)
    131 / 208 (62.98%)
         occurrences all number
    367
    425
    Fatigue
         subjects affected / exposed
    38 / 209 (18.18%)
    47 / 208 (22.60%)
         occurrences all number
    64
    102
    Mucosal inflammation
         subjects affected / exposed
    44 / 209 (21.05%)
    49 / 208 (23.56%)
         occurrences all number
    78
    92
    Oedema peripheral
         subjects affected / exposed
    12 / 209 (5.74%)
    16 / 208 (7.69%)
         occurrences all number
    14
    28
    Pyrexia
         subjects affected / exposed
    25 / 209 (11.96%)
    48 / 208 (23.08%)
         occurrences all number
    32
    72
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    21 / 209 (10.05%)
    24 / 208 (11.54%)
         occurrences all number
    30
    31
    Dyspnoea
         subjects affected / exposed
    31 / 209 (14.83%)
    33 / 208 (15.87%)
         occurrences all number
    46
    42
    Dyspnoea exertional
         subjects affected / exposed
    11 / 209 (5.26%)
    0 / 208 (0.00%)
         occurrences all number
    12
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    16 / 209 (7.66%)
    16 / 208 (7.69%)
         occurrences all number
    21
    27
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    18 / 209 (8.61%)
    20 / 208 (9.62%)
         occurrences all number
    42
    51
    Aspartate aminotransferase increased
         subjects affected / exposed
    21 / 209 (10.05%)
    22 / 208 (10.58%)
         occurrences all number
    37
    56
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 209 (0.00%)
    14 / 208 (6.73%)
         occurrences all number
    0
    26
    Blood creatinine increased
         subjects affected / exposed
    22 / 209 (10.53%)
    28 / 208 (13.46%)
         occurrences all number
    39
    45
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 209 (0.00%)
    14 / 208 (6.73%)
         occurrences all number
    0
    23
    White blood cell count decreased
         subjects affected / exposed
    23 / 209 (11.00%)
    18 / 208 (8.65%)
         occurrences all number
    190
    150
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 209 (0.00%)
    11 / 208 (5.29%)
         occurrences all number
    0
    13
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    16 / 209 (7.66%)
    11 / 208 (5.29%)
         occurrences all number
    16
    11
    Dysgeusia
         subjects affected / exposed
    23 / 209 (11.00%)
    25 / 208 (12.02%)
         occurrences all number
    27
    38
    Headache
         subjects affected / exposed
    33 / 209 (15.79%)
    42 / 208 (20.19%)
         occurrences all number
    52
    61
    Insomnia
         subjects affected / exposed
    28 / 209 (13.40%)
    31 / 208 (14.90%)
         occurrences all number
    36
    46
    Neuropathy peripheral
         subjects affected / exposed
    19 / 209 (9.09%)
    0 / 208 (0.00%)
         occurrences all number
    23
    0
    Paraesthesia
         subjects affected / exposed
    0 / 209 (0.00%)
    17 / 208 (8.17%)
         occurrences all number
    0
    25
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    142 / 209 (67.94%)
    141 / 208 (67.79%)
         occurrences all number
    577
    552
    Febrile neutropenia
         subjects affected / exposed
    0 / 209 (0.00%)
    19 / 208 (9.13%)
         occurrences all number
    0
    21
    Leukopenia
         subjects affected / exposed
    0 / 209 (0.00%)
    17 / 208 (8.17%)
         occurrences all number
    0
    31
    Lymphopenia
         subjects affected / exposed
    0 / 209 (0.00%)
    13 / 208 (6.25%)
         occurrences all number
    0
    31
    Neutropenia
         subjects affected / exposed
    141 / 209 (67.46%)
    125 / 208 (60.10%)
         occurrences all number
    767
    650
    Thrombocytopenia
         subjects affected / exposed
    134 / 209 (64.11%)
    129 / 208 (62.02%)
         occurrences all number
    579
    488
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    11 / 209 (5.26%)
    11 / 208 (5.29%)
         occurrences all number
    13
    16
    Abdominal distension
         subjects affected / exposed
    12 / 209 (5.74%)
    16 / 208 (7.69%)
         occurrences all number
    14
    17
    Abdominal pain
         subjects affected / exposed
    55 / 209 (26.32%)
    58 / 208 (27.88%)
         occurrences all number
    94
    89
    Abdominal pain lower
         subjects affected / exposed
    11 / 209 (5.26%)
    0 / 208 (0.00%)
         occurrences all number
    11
    0
    Abdominal pain upper
         subjects affected / exposed
    48 / 209 (22.97%)
    35 / 208 (16.83%)
         occurrences all number
    72
    45
    Constipation
         subjects affected / exposed
    99 / 209 (47.37%)
    100 / 208 (48.08%)
         occurrences all number
    189
    187
    Diarrhoea
         subjects affected / exposed
    49 / 209 (23.44%)
    61 / 208 (29.33%)
         occurrences all number
    81
    98
    Dry mouth
         subjects affected / exposed
    0 / 209 (0.00%)
    11 / 208 (5.29%)
         occurrences all number
    0
    15
    Dyspepsia
         subjects affected / exposed
    17 / 209 (8.13%)
    15 / 208 (7.21%)
         occurrences all number
    23
    23
    Nausea
         subjects affected / exposed
    138 / 209 (66.03%)
    134 / 208 (64.42%)
         occurrences all number
    326
    320
    Vomiting
         subjects affected / exposed
    65 / 209 (31.10%)
    63 / 208 (30.29%)
         occurrences all number
    119
    105
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    24 / 209 (11.48%)
    17 / 208 (8.17%)
         occurrences all number
    25
    21
    Dry skin
         subjects affected / exposed
    0 / 209 (0.00%)
    17 / 208 (8.17%)
         occurrences all number
    0
    18
    Erythema
         subjects affected / exposed
    0 / 209 (0.00%)
    17 / 208 (8.17%)
         occurrences all number
    0
    22
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    16 / 209 (7.66%)
    27 / 208 (12.98%)
         occurrences all number
    25
    53
    Pruritus
         subjects affected / exposed
    16 / 209 (7.66%)
    32 / 208 (15.38%)
         occurrences all number
    21
    54
    Rash
         subjects affected / exposed
    26 / 209 (12.44%)
    41 / 208 (19.71%)
         occurrences all number
    44
    89
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 209 (0.00%)
    30 / 208 (14.42%)
         occurrences all number
    0
    34
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    43 / 209 (20.57%)
    44 / 208 (21.15%)
         occurrences all number
    66
    73
    Back pain
         subjects affected / exposed
    30 / 209 (14.35%)
    33 / 208 (15.87%)
         occurrences all number
    34
    48
    Myalgia
         subjects affected / exposed
    14 / 209 (6.70%)
    14 / 208 (6.73%)
         occurrences all number
    20
    20
    Pain in extremity
         subjects affected / exposed
    14 / 209 (6.70%)
    20 / 208 (9.62%)
         occurrences all number
    18
    25
    Infections and infestations
    COVID-19
         subjects affected / exposed
    21 / 209 (10.05%)
    27 / 208 (12.98%)
         occurrences all number
    23
    27
    Urinary tract infection
         subjects affected / exposed
    23 / 209 (11.00%)
    31 / 208 (14.90%)
         occurrences all number
    40
    49
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    53 / 209 (25.36%)
    50 / 208 (24.04%)
         occurrences all number
    90
    76
    Hyperglycaemia
         subjects affected / exposed
    17 / 209 (8.13%)
    16 / 208 (7.69%)
         occurrences all number
    25
    29
    Hypokalaemia
         subjects affected / exposed
    14 / 209 (6.70%)
    19 / 208 (9.13%)
         occurrences all number
    28
    29
    Hypomagnesaemia
         subjects affected / exposed
    44 / 209 (21.05%)
    40 / 208 (19.23%)
         occurrences all number
    91
    91

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Apr 2019
    The rationale for the amended includes several relevant issues: Safety information has been updated due to the update of niraparib and atezolizumab investigator brochure: - Thromboembolic events has been added as a potential AESI of niraparib, exclusion criteria related to niraparib has been modified. - Atezolizumab immune-related nephritis and immune-related myositis management guidelines have been included. - A new exploratory objective and exploratory endpoint have been added. - Eligibility criteria have been modified. - Clarifications in both arms of the study have been added related to administration of medication. - Study calendar has been updated to add new clarifications and for consistency. - Indications for sample management have been referred to the lab manual. - Minor text accuracy edits/corrections have been performed.
    06 Jun 2019
    The rationale for the amended includes several relevant issues: PD-L1 has been considered as a new stratification factor, thus, rationale for stratification has been added and some sections of the protocol have been modified accordingly: - Study schema - Study flow chart - Table of assessments - Randomization process - Statistical considerations - Study objectives - Eligibility criteria: Mandatory de novo tumor biopsy sent to central laboratory for PD-L1 status determination has been added as an inclusion criterion. In addition, two additional tumour samples are needed for exploratory PD-L1 testing and biomarkers. - Tumor samples management directions Permitted time to hold the atezolizumab/placebo treatment in patients tapered off steroids used to treat adverse events has been updated from > 42 days to > 12 weeks. Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal is no longer limited to patient treated with pegylated liposomal doxorubicin only. Administration of a live, attenuated vaccine (including against influenza) is not permitted within 5 months after the final dose of atezolizumab. Safety information has been updated: occurrence of auto-immune disease will be declared as an adverse event of special interest at any time during atezolizumab/placebo treatment and at any time after the treatment has been stopped (previously declared as serious adverse event (SAE)). Protocol Deviations term and definition has been updated to “Serious Breaches” as per current regulation. Minor text accuracy edits/corrections have been performed.
    11 Aug 2020
    Due to Atezolizumab IB update from version 14 to version 15 addendum 2, management of adverse events associated with atezolizumab and other safety issues has been updated: - Changes in atezolizumab AESIs. - Different wording of immunological AEs: immune-mediated instead of immune-related. - Changes in atezolizumab SAEs management wording and procedure and possibility to use another corticosteroid different than prednisone. - New section added in SAEs management: Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome. “Fresh tumor” specimens for PD-L1 status determination has been referenced as “de novo” tumor specimens to avoid misunderstandings. Eligibility criteria: Exclusion Criteria 24: the following exceptions to patients with history of autoimmune disease have been added: Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriasis arthritis would be excluded) provided that they meet all of the following conditions: - Rash must cover less than 10% of body surface area. - Disease is well controlled at baseline and requires only low potency topical steroids: • No acute exacerbations of underlying condition within the previous 12 months (i.e., does not require psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids) Exclusion Criteria 32: New requisition on the iPARP exposure duration has been added: The duration of exposure to PARPi following front line therapy need to be ≥18 months for BRCA mutated patients and ≥ 12 months for BRCA wild type patients. Tumor Samples: Requirements on the “de novo” biopsy have been added: In order to have a very low percentage on non-informative PD-L1, blocks must be provided with a maximal of tumoral cellularity. Sample fixation conditions have been modified.
    26 May 2021
    The following amendment has been performed mainly due to new safety information related with the study investigational medicinal products. Management guidelines of adverse events associated with atezolizumab has been updated. After discussion with the Independent Data Monitoring Committee and in the Steering Committee, it was agreed and proposed that FFPE from archival tissue may be acceptable for ANITA patient randomization if the mandatory de novo biopsy is technically not possible or failed to produce enough representative tumor tissue, and after sponsor approval. The current protocol states that mandatory de novo tumor biopsy (collected within 3 months prior to randomization) is needed for patient randomization. This change, which modifies inclusion criteria 9, is implemented at the request of principal investigators, who claim that the novo biopsy is sometimes technically not possible or failed to produce enough representative tumor tissue, causing patient screening failures, with a detrimental effect in the trial recruitment rate that should be finalised by August 2021. Due to the request by the principal investigators, as it was not previously defined, GEICO has considered to added apixaban as an allowed medication in patients who require therapeutic anticoagulation. In the original protocol, the analysis of PFS, which is the primary endpoint, was determined to be performed after 254 events had occurred, which correspond to approximately 60% of events. Based on the results of recent phase III trials with checkpoint inhibitors in ovarian cancer, both in the front line (IMAGYN050) and recurrent setting (JAVELIN 200), we have learned that the differences in PFS are better observed and detected with longer follow-up. Based on this observation, we plan to perform the primary analysis when 332 events have occurred, which is approximately 80% of events. With this change, we will improve the power of detecting a positive effect with the addition of atezolizumab.
    24 Aug 2022
    Due to Atezolizumab IB update from version 17 to version 18, protocol was updated with new safety information regarding changes in the management of Atezolizumab-specific adverse events. Also study personnel, study timelines, atezolizumab clinical experience section and other minor changes have been updated.
    13 Jul 2023
    Due to the update of the Atezolizumab IB from version 18 to version 19, the protocol was updated with new safety information. Based on previous data, patients will receive a maximum of 24 months of treatment. ATA and PK will not be analysed. An unblinded pre-final analysis will be performed once the expected number of events has been reached.
    28 May 2024
    Due to Atezolizumab IB update from version 19 to version 20, protocol was updated with new safety information, including changes in the management of atezolizumab-specific adverse events and new warnings and precautions. Atezolizumab indications have also been updated.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    21 Jun 2019
    The sponsor processed a relevant modification related to the protocol of the reference trial to determine the PD-L1 status of the patients to be included in the trial, with the aim of exploring the correlation between PD-L1 expression status in archival tissue and in fresh tumour samples in line with what has been done in other clinical trials, and echoing the latest results obtained in similar clinical trials. Given that recruitment for the study was ahead of schedule and that it would take several weeks to process the relevant modification until authorisation, which would imply the inclusion of a large number of patients for whom PD-L1 determination would not be available, the sponsor decided to halt recruitment until authorisation of the relevant modification in order to have as many patients as possible with PD-L1 determination available for data analysis.
    22 Oct 2019

    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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