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    Clinical Trial Results:
    A Phase III, Double-Blind, Placebo-Controlled, Randomized Study of Taselisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women With Estrogen Receptor-Positive And Her2-Negative Locally Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatases Inhibitor Therapy

    Summary
    EudraCT number
    		 2014-003185-25
    Trial protocol
    		 IT   PT   ES   CZ   DE   AT   NL   PL   BG   FR   SE   GR   RO   FI  
    Global end of trial date
    29 Jun 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    29 Jun 2022
    First version publication date
    19 Jun 2019
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GO29058
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02340221
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    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
    29 Jun 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jun 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of this study was to compare the efficacy between taselisib + fulvestrant versus placebo + fulvestrant as measured by investigator-assessed progression-free survival (PFS) in postmenopausal women with estrogen receptor-positive and human epidermal receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutant tumors, who had disease recurrence or progression during or after aromatase inhibitor therapy.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Apr 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Austria: 9
    Country: Number of subjects enrolled
    Bulgaria: 22
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 1
    Country: Number of subjects enrolled
    Canada: 64
    Country: Number of subjects enrolled
    China: 21
    Country: Number of subjects enrolled
    Colombia: 4
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    Finland: 2
    Country: Number of subjects enrolled
    France: 32
    Country: Number of subjects enrolled
    Greece: 12
    Country: Number of subjects enrolled
    Italy: 40
    Country: Number of subjects enrolled
    Korea, Republic of: 60
    Country: Number of subjects enrolled
    Mexico: 32
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Peru: 20
    Country: Number of subjects enrolled
    Poland: 44
    Country: Number of subjects enrolled
    Portugal: 23
    Country: Number of subjects enrolled
    Romania: 30
    Country: Number of subjects enrolled
    Russian Federation: 23
    Country: Number of subjects enrolled
    Serbia: 10
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    Thailand: 5
    Country: Number of subjects enrolled
    Turkey: 20
    Country: Number of subjects enrolled
    Taiwan: 10
    Country: Number of subjects enrolled
    United States: 43
    Worldwide total number of subjects
    631
    EEA total number of subjects
    283
    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)
    430
    From 65 to 84 years
    198
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 155 centers in 28 countries.

    Pre-assignment
    Screening details
    		 The study enrolled postmenopausal women with estrogen receptor-positive and HER2-negative locally advanced or metastatic breast cancer. Randomisation was stratified by three factors: 1) visceral versus non-visceral disease, 2) sensitivity versus non-sensitivity to most recent endocrine therapy, and 3) geographical region.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo+Fulvestrant
    Arm description
    		 Subjects received taselisib-matching placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28‑day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received taselisib-matching placebo orally QD beginning at Cycle 1, Day 1 until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received fulvestrant 500 mg IM injection on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Arm title
    		 Taselisib+Fulvestrant
    Arm description
    		 Subjects received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Taselisib
    Investigational medicinal product code
    RO5537381
    Other name
    GDC-0032
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received taselisib 4 mg orally QD beginning at Cycle 1, Day 1 until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received fulvestrant 500 mg IM injection on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Number of subjects in period 1
    		Placebo+Fulvestrant Taselisib+Fulvestrant
    Started
    214
    417
    Completed
    0
    0
    Not completed
    214
    417
         Death
    100
    197
         Reason Not Specified
    85
    165
         Withdrawal by Subject
    24
    37
         Study Terminated by Sponsor
    1
    3
         Lost to follow-up
    4
    15

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo+Fulvestrant
    Reporting group description
    		 Subjects received taselisib-matching placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28‑day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Reporting group title
    Taselisib+Fulvestrant
    Reporting group description
    		 Subjects received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Reporting group values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant Total
    Number of subjects
    		 214 417 631
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.7 ± 10.0 60.1 ± 9.9 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 214 417 631
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Placebo+Fulvestrant
    Reporting group description
    		 Subjects received taselisib-matching placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28‑day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Reporting group title
    Taselisib+Fulvestrant
    Reporting group description
    		 Subjects received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Primary: Progression-Free Survival (PFS) in Subjects with PIK3CA-mutant Tumours as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) at Primary Analysis

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    End point title
    		 Progression-Free Survival (PFS) in Subjects with PIK3CA-mutant Tumours as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) at Primary Analysis
    End point description
    PFS was defined as the time from randomisation to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimetres (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Primary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    5.39 (3.68 to 7.29)
    7.43 (7.26 to 9.07)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0037
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 0.89

    Primary: PFS in Subjects with PIK3CA-mutant Tumours as Assessed by Investigator Using RECIST v1.1 at Final Analysis

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    End point title
    		 PFS in Subjects with PIK3CA-mutant Tumours as Assessed by Investigator Using RECIST v1.1 at Final Analysis
    End point description
    PFS was defined as the time from randomisation to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Primary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    5.55 (3.75 to 7.33)
    8.05 (7.33 to 9.10)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0008
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.87

    Secondary: Percentage of Subjects with Objective Response (Partial Response [PR] plus Complete Response [CR]), as Assessed Using RECIST v.1.1 at Primary Analysis

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    End point title
    		 Percentage of Subjects with Objective Response (Partial Response [PR] plus Complete Response [CR]), as Assessed Using RECIST v.1.1 at Primary Analysis
    End point description
    PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalisation of tumor marker levels (as applicable to non-target lesions). Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    134
    264
    Units: percentage of subjects
        number (confidence interval 95%)
    11.9 (7.1 to 18.3)
    28.0 (22.7 to 33.8)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 5.4

    Secondary: Overall Survival (OS) at Primary Analysis

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    End point title
    		 Overall Survival (OS) at Primary Analysis
    End point description
    OS was defined as the time from the date of randomisation to the date of death due to any cause. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point. 99999 represents that the upper limit of confidence interval was not estimable due to the low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From randomisation up to death from any cause (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    23.56 (18.00 to 99999)
    26.81 (21.29 to 99999)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4151
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.25

    Secondary: Percentage of Subjects with Clinical Benefit, as Assessed According to RECIST v1.1 at Primary Analysis

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    End point title
    		 Percentage of Subjects with Clinical Benefit, as Assessed According to RECIST v1.1 at Primary Analysis
    End point description
    Clinical benefit:objective response (PR+CR),or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomisation.PR:at least a 30% decrease in sum of diameters of target lesions,taking as reference baseline sum of diameters.CR:disappearance of all target and non-target lesions and normalisation of tumor marker levels.Disease progression:at least a 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study,including baseline.In addition to relative increase of 20%,sum must also demonstrate absolute increase of at least 5 mm.For non-target lesions,disease progression:unequivocal progression of existing lesions.Appearance of one or more new lesions was also considered progression.Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline,regardless of whether they received any amount of study treatment.Number of subjects analysed is number of subjects with data available at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    134
    264
    Units: percentage of subjects
        number (confidence interval 95%)
    37.3 (29.1 to 45.7)
    51.5 (45.3 to 57.7)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 2.9

    Secondary: Duration of Objective Response (DOR), as Assessed by Investigator Using RECIST v1.1 at Primary Analysis

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    End point title
    		 Duration of Objective Response (DOR), as Assessed by Investigator Using RECIST v1.1 at Primary Analysis
    End point description
    DOR:time from first tumor assessment for objective response to first documented disease progression or death due to any cause, whichever occurred first. CR:disappearance of all target and non-target lesions and normalisation of tumor marker levels.PR:at least a 30% decrease in the sum of diameters of target lesions,taking as reference baseline sum of diameters. Disease progression:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline.For non-target lesions, disease progression:unequivocal progression of existing lesions.Appearance of one or more new lesions was also considered progression.Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Number analysed:number of subjects with data available for analysis at given timepoint. 99999=upper limit of CI was not estimable due to low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    16
    74
    Units: months
        median (confidence interval 95%)
    7.23 (6.51 to 99999)
    8.74 (5.72 to 11.24)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6708
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 2.59

    Secondary: PFS as Assessed by Blinded Independent Central Review (BICR) Using RECIST v1.1 at Primary Analysis

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    End point title
    		 PFS as Assessed by Blinded Independent Central Review (BICR) Using RECIST v1.1 at Primary Analysis
    End point description
    PFS was defined as the time from randomisation to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    5.39 (3.68 to 9.23)
    8.97 (7.39 to 9.49)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0023
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.86

    Secondary: Percentage of Subjects with Adverse Events (AEs) at Primary Analysis

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    End point title
    		 Percentage of Subjects with Adverse Events (AEs) at Primary Analysis
    End point description
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The safety-evaluable population included all randomised subjects who received at least one dose of taselisib or placebo or fulvestrant. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation up to the 15 Oct 2017 data cutoff, approximately 2.5 years
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    213
    416
    Units: percentage of subjects
        number (not applicable)
    89.7
    95.4
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Taselisib

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Taselisib [1]
    End point description
    The Pharmacokinetic (PK) population included all subjects who received at least one dose of taselisib and provided valid (adequately documented dose time and PK sample time) PK assessments. "n" is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    1 to 4 hours (hrs) post-dose on Cycle (C) 1, Day (D) 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1 (each cycle=28 days)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are reported only for the taselisib treatment arm.
    End point values
    		 Taselisib+Fulvestrant
    Number of subjects analysed
    417
    Units: ng/mL
    arithmetic mean (standard deviation)
        C1D1 (n= 391)
    18.2 ± 14.6
        C2D1 (n=359)
    66.6 ± 35.2
    No statistical analyses for this end point

    Secondary: Minimum Observed Plasma Concentration (Cmin) of Taselisib

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    End point title
    		 Minimum Observed Plasma Concentration (Cmin) of Taselisib [2]
    End point description
    The PK population included all subjects who received at least one dose of taselisib and provided valid (adequately documented dose time and PK sample time) PK assessments. "n" is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    1 to 4 hrs post-dose on Cycle 1, Day 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1; 0 to 3 hrs pre-dose on Cycle 6, Day 1 (each cycle=28 days)
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are reported only for the taselisib treatment arm.
    End point values
    		 Taselisib+Fulvestrant
    Number of subjects analysed
    417
    Units: ng/mL
    arithmetic mean (standard deviation)
        C2D1 (n=377)
    42.8 ± 26.6
        C6D1 (n=213)
    35.3 ± 31.5
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score

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    End point title
    		 Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score
    End point description
    The EORTC QLQ-C30 consists of 30 questions that comprise aspects of subject's functioning assessment (physical, emotional, role, cognitive, and social); symptom scales (fatigue; nausea, vomiting, and pain; the global health/quality of life [QoL]); and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties), within a recall period of “the past week.” Most questions used a 4-point scale (1=Not at all to 4=Very much; two questions used a 7-point scale (1=Very poor to 7=Excellent). Scores were averaged and transformed to a 0-100 scale; a higher score for Global Qol/functional scales=better level of functioning; a higher score for symptom scale=greater degree of symptoms. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. "n" is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, C2D1 up to C7D1 (each cycle=28 days)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: score on a scale
    arithmetic mean (standard deviation)
        Appetite Loss:Baseline (n=159, 312)
    15.9 ± 25.9
    15.3 ± 23.3
        Appetite Loss: Change at C2D1 (n=147, 292)
    -0.2 ± 25.7
    6.2 ± 26.2
        Appetite Loss: Change at C3D1 (n=117, 260)
    -4.3 ± 27.2
    8.7 ± 28.1
        Appetite Loss: Change at C4D1 (n=100, 231)
    -1.7 ± 26.1
    8.4 ± 28.1
        Appetite Loss: Change at C5D1 (n=75, 206)
    -0.4 ± 26.6
    6.0 ± 27.2
        Appetite Loss: Change at C6D1 (n=66, 171)
    -0.5 ± 22.3
    6.6 ± 27.2
        Appetite Loss: Change at C7D1 (n=58, 145)
    -5.7 ± 28.7
    4.6 ± 26.5
        Cognitive Functioning: Baseline (n=160, 312)
    85.3 ± 18.1
    85.9 ± 18.7
        Cognitive Functioning: Change at C2D1 (n=147, 292)
    0.7 ± 16.5
    -1.1 ± 16.8
        Cognitive Functioning: Change at C3D1 (n=117, 260)
    0.9 ± 17.9
    -2.9 ± 19.1
        Cognitive Functioning: Change at C4D1 (n=100, 231)
    1.8 ± 18.9
    -1.7 ± 18.4
        Cognitive Functioning: Change at C5D1 (n=76, 207)
    -1.5 ± 17.7
    -3.2 ± 17.7
        Cognitive Functioning: Change at C6D1 (n=66, 171)
    -0.5 ± 18.5
    -2.8 ± 17.6
        Cognitive Functioning: Change at C7D1 (n=58, 145)
    -2.3 ± 18.1
    -0.8 ± 18.8
        Constipation: Baseline (n=160, 312)
    15.8 ± 23.9
    14.5 ± 23.7
        Constipation: Change at C2D1 (n=147, 291)
    0.0 ± 24.0
    -6.0 ± 21.1
        Constipation: Change at C3D1 (n=117, 260)
    -2.3 ± 25.0
    -4.9 ± 20.8
        Constipation: Change at C4D1 (n=99, 231)
    -2.7 ± 24.6
    -5.5 ± 22.0
        Constipation: Change at C5D1 (n=76, 207)
    -1.3 ± 22.7
    -4.0 ± 21.0
        Constipation: Change at C6D1 (n=66, 170)
    -3.0 ± 27.3
    -3.5 ± 21.8
        Constipation: Change at C7D1 (n=58, 145)
    -4.6 ± 24.5
    -6.9 ± 22.5
        Diarrhoea: Baseline (n=159, 311)
    6.3 ± 15.1
    5.0 ± 14.4
        Diarrhoea: Change at C2D1 (n=147, 292)
    -0.5 ± 17.9
    10.2 ± 22.4
        Diarrhoea: Change at C3D1 (n=117, 260)
    -0.9 ± 16.6
    13.7 ± 26.3
        Diarrhoea: Change at C4D1 (n=100, 231)
    -2.7 ± 21.0
    13.1 ± 28.9
        Diarrhoea: Change at C5D1 (n=76, 207)
    -2.6 ± 19.4
    11.1 ± 27.7
        Diarrhoea: Change at C6D1 (n=66, 171)
    -2.0 ± 17.4
    14.0 ± 29.1
        Diarrhoea: Change at C7D1 (n=58, 145)
    1.1 ± 20.7
    15.6 ± 30.9
        Dyspnoea: Baseline (n=160, 311)
    15.0 ± 23.0
    15.4 ± 22.2
        Dyspnoea: Change at C2D1 (n=146, 291)
    4.1 ± 23.5
    -2.1 ± 19.5
        Dyspnoea: Change at C3D1 (n=117, 260)
    2.8 ± 20.3
    0.0 ± 20.9
        Dyspnoea: Change at C4D1 (n=100, 231)
    0.7 ± 23.2
    0.0 ± 23.3
        Dyspnoea: Change at C5D1 (n=76, 207)
    2.6 ± 26.5
    1.6 ± 23.2
        Dyspnoea: Change at C6D1 (n=66, 170)
    3.0 ± 26.6
    0.2 ± 23.4
        Dyspnoea: Change at C7D1 (n=58, 145)
    1.7 ± 24.5
    -2.1 ± 21.2
        Emotional Functioning: Baseline (n=160, 312)
    73.1 ± 22.1
    71.9 ± 22.1
        Emotional Functioning: Change at C2D1 (n=147, 292)
    4.0 ± 17.9
    5.1 ± 18.5
        Emotional Functioning: Change at C3D1 (n=117, 260)
    4.5 ± 19.1
    2.3 ± 21.6
        Emotional Functioning: Change at C4D1 (n=100, 231)
    4.5 ± 18.5
    2.6 ± 19.7
        Emotional Functioning: Change at C5D1 (n=76, 207)
    5.2 ± 20.1
    -0.4 ± 21.8
        Emotional Functioning: Change at C6D1 (n=66, 171)
    2.1 ± 20.5
    2.4 ± 21.6
        Emotional Functioning: Change at C7D1 (n=58, 145)
    5.3 ± 20.7
    2.8 ± 19.7
        Fatigue: Baseline (n=160, 312)
    30.8 ± 22.5
    30.8 ± 22.0
        Fatigue: Change at C2D1 (n=147, 292)
    2.0 ± 19.2
    -0.5 ± 18.8
        Fatigue: Change at C3D1 (n=117, 260)
    -1.5 ± 19.5
    1.8 ± 21.5
        Fatigue: Change at C4D1 (n=100, 231)
    -0.2 ± 19.1
    2.4 ± 21.9
        Fatigue: Change at C5D1 (n=76, 207)
    -0.1 ± 20.8
    2.8 ± 20.4
        Fatigue: Change at C6D1 (n=66, 171)
    3.3 ± 20.0
    2.4 ± 20.5
        Fatigue: Change at C7D1 (n=58, 145)
    1.0 ± 20.0
    1.8 ± 20.5
        Financial Difficulties: Baseline(n=160,310)
    18.5 ± 25.8
    19.2 ± 27.1
        Financial Difficulties:Change at C2D1(n=147,287)
    -1.1 ± 20.4
    -2.8 ± 21.4
        Financial Difficulties:Change at C3D1(n=117,258)
    -0.9 ± 24.9
    -1.6 ± 24.4
        Financial Difficulties:Change at C4D1(n=100,230)
    0.7 ± 25.1
    -0.3 ± 23.7
        Financial Difficulties:Change at C5D1(n=76,205)
    -0.4 ± 28.0
    0.3 ± 24.9
        Financial Difficulties:Change at C6D1(n=66,169)
    5.6 ± 30.1
    0.4 ± 23.6
        Financial Difficulties:Change at C7D1(n=58,143)
    -0.6 ± 26.1
    2.1 ± 23.1
        Global Health Status/QoL:Baseline(n=160,311)
    65.2 ± 18.4
    67.4 ± 20.3
        Global Health Status/QoL:Change at C2D1(n=147,291)
    -0.1 ± 16.7
    1.0 ± 19.9
        Global Health Status/QoL:Change at C3D1(n=117,259)
    -1.0 ± 18.5
    -1.5 ± 20.9
        Global Health Status/QoL:Change at C4D1(n=100,230)
    -1.5 ± 18.6
    -1.6 ± 20.3
        Global Health Status/QoL:Change at C5D1(n=76,207)
    0.3 ± 19.9
    -2.8 ± 20.3
        Global Health Status/QoL:Change at C6D1(n=66,171)
    -1.6 ± 18.6
    -3.4 ± 19.5
        Global Health Status/QoL: Change at C7D1(n=58,145)
    -1.1 ± 18.9
    -1.0 ± 18.9
        Insomnia: Baseline (n=160, 311)
    26.0 ± 27.6
    26.5 ± 27.7
        Insomnia: Change at C2D1 (n=146, 289)
    -0.9 ± 24.4
    -3.8 ± 23.7
        Insomnia: Change at C3D1 (n=117, 260)
    -3.4 ± 30.1
    -4.1 ± 26.4
        Insomnia: Change at C4D1 (n=100, 231)
    -4.0 ± 28.9
    -1.0 ± 26.8
        Insomnia: Change at C5D1 (n=76, 206)
    -0.4 ± 29.1
    -3.9 ± 25.6
        Insomnia: Change at C6D1 (n=66, 170)
    -2.0 ± 30.3
    -2.4 ± 28.2
        Insomnia: Change at C7D1 (n=57, 145)
    -4.1 ± 28.2
    -1.8 ± 27.2
        Nausea/Vomiting: Baseline (n=160, 312)
    5.9 ± 13.4
    6.7 ± 13.7
        Nausea/Vomiting: Change at C2D1 (n=147, 292)
    0.1 ± 11.9
    1.6 ± 18.1
        Nausea/Vomiting: Change at C3D1 (n=117, 260)
    0.7 ± 15.2
    2.2 ± 17.6
        Nausea/Vomiting: Change at C4D1 (n=100, 231)
    0.3 ± 17.9
    2.3 ± 18.6
        Nausea/Vomiting: Change at C5D1 (n=76, 207)
    -1.1 ± 18.3
    0.5 ± 15.4
        Nausea/Vomiting: Change at C6D1 (n=66, 171)
    1.5 ± 18.0
    -0.6 ± 15.9
        Nausea/Vomiting: Change at C7D1 (n=58, 145)
    2.6 ± 15.5
    2.2 ± 18.8
        Pain: Baseline (n=160, 312)
    28.0 ± 25.4
    27.1 ± 24.9
        Pain: Change at C2D1 (n=147, 292)
    -0.2 ± 24.0
    -5.0 ± 20.8
        Pain: Change at C3D1 (n=117, 260)
    -3.7 ± 23.3
    -3.5 ± 22.6
        Pain: Change at C4D1 (n=100, 231)
    -3.2 ± 24.7
    -1.7 ± 24.2
        Pain: Change at C5D1 (n=76, 207)
    -3.3 ± 24.2
    -4.3 ± 22.9
        Pain: Change at C6D1 (n=66, 171)
    -1.0 ± 23.0
    -2.2 ± 22.5
        Pain: Change at C7D1 (n=58, 145)
    0.3 ± 23.5
    -4.4 ± 19.8
        Physical Functioning: Baseline (n=160, 311)
    76.7 ± 19.9
    78.4 ± 18.8
        Physical Functioning: Change at C2D1 (n=147, 292)
    -1.1 ± 13.4
    1.6 ± 12.7
        Physical Functioning: Change at C3D1 (n=117, 260)
    2.0 ± 14.1
    0.8 ± 15.7
        Physical Functioning: Change at C4D1 (n=100, 231)
    1.5 ± 16.1
    0.3 ± 15.7
        Physical Functioning: Change at C5D1 (n=76, 207)
    2.0 ± 17.7
    1.0 ± 13.5
        Physical Functioning: Change at C6D1 (n=66, 171)
    0.9 ± 18.4
    1.1 ± 14.9
        Physical Functioning: Change at C7D1 (n=58, 145)
    1.6 ± 16.2
    0.6 ± 14.2
        Role Functioning: Baseline (n=160, 312)
    79.1 ± 24.6
    78.7 ± 24.0
        Role Functioning: Change at C2D1 (n=147, 292)
    -2.0 ± 19.3
    1.7 ± 21.5
        Role Functioning: Change at C3D1 (n=117, 260)
    -0.4 ± 23.4
    -1.0 ± 23.9
        Role Functioning: Change at C4D1 (n=100, 231)
    0.3 ± 23.0
    0.4 ± 24.2
        Role Functioning: Change at C5D1 (n=76, 207)
    1.8 ± 22.5
    -1.6 ± 21.6
        Role Functioning: Change at C6D1 (n=66, 171)
    -1.3 ± 23.8
    -1.6 ± 23.4
        Role Functioning: Change at C7D1 (n=58, 145)
    -0.3 ± 22.6
    0.0 ± 22.9
        Social Functioning: Baseline (n=160, 312)
    83.2 ± 21.8
    81.2 ± 23.1
        Social Functioning: Change at C2D1 (n=147, 292)
    -0.8 ± 19.9
    2.7 ± 20.0
        Social Functioning: Change at C3D1 (n=117, 259)
    1.3 ± 21.9
    -0.8 ± 23.2
        Social Functioning: Change at C4D1 (n=100, 231)
    1.8 ± 18.2
    -0.5 ± 21.3
        Social Functioning: Change at C5D1 (n=76, 207)
    0.9 ± 19.4
    -1.0 ± 23.3
        Social Functioning: Change at C6D1 (n=66, 170)
    -0.8 ± 20.1
    -1.6 ± 23.4
        Social Functioning: Change at C7D1 (n=58, 145)
    0.6 ± 21.2
    0.1 ± 19.7
    No statistical analyses for this end point

    Secondary: Change From Baseline in Modified EORTC Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) Score

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    End point title
    		 Change From Baseline in Modified EORTC Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) Score
    End point description
    EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to a 0-100 scale. Higher scores for the functional scales indicated a higher/better level of functioning/healthy functioning. Higher scores for the symptom scales indicated worse symptoms. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. "n" is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, C2D1 up to C7D1 (each cycle=28 days)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: score on a scale
    arithmetic mean (standard deviation)
        Arm Symptoms: Baseline (n=152, 304)
    15.5 ± 18.8
    19.3 ± 21.1
        Arm Symptoms: Change at C2D1 (n=140, 282)
    0.1 ± 17.4
    -5.4 ± 15.6
        Arm Symptoms: Change at C3D1 (n=111, 250)
    -0.7 ± 19.5
    -6.1 ± 17.4
        Arm Symptoms: Change at C4D1 (n=95, 219)
    -1.4 ± 21.9
    -5.8 ± 15.8
        Arm Symptoms: Change at C5D1 (n=72, 203)
    0.8 ± 17.0
    -6.6 ± 15.7
        Arm Symptoms: Change at C6D1 (n=63, 167)
    1.1 ± 20.8
    -5.0 ± 18.5
        Arm Symptoms: Change at C7D1 (n=57, 140)
    -1.2 ± 19.7
    -6.0 ± 15.2
        Body Image: Baseline (n=149, 300)
    82.0 ± 21.7
    80.8 ± 22.5
        Body Image: Change at C2D1 (n=135, 276)
    1.8 ± 14.9
    1.5 ± 16.5
        Body Image: Change at C3D1 (n=106, 242)
    1.6 ± 18.0
    1.1 ± 20.6
        Body Image: Change at C4D1 (n=92, 214)
    1.1 ± 17.8
    1.8 ± 20.6
        Body Image: Change at C5D1 (n=68, 198)
    0.2 ± 19.5
    0.0 ± 17.5
        Body Image: Change at C6D1 (n=60, 164)
    1.1 ± 21.0
    0.4 ± 18.2
        Body Image: Change at C7D1 (n=54, 137)
    5.6 ± 18.8
    -0.3 ± 18.2
        Breast Symptoms: Baseline (n=151, 304)
    8.7 ± 14.6
    11.0 ± 14.1
        Breast Symptoms: Change at C2D1 (n=139, 282)
    0.0 ± 13.7
    -3.0 ± 11.8
        Breast Symptoms: Change at C3D1 (n=112, 250)
    -0.8 ± 13.3
    -3.5 ± 11.6
        Breast Symptoms: Change at C4D1 (n=95, 220)
    0.1 ± 14.2
    -3.0 ± 11.8
        Breast Symptoms: Change at C5D1 (n=72, 203)
    -0.9 ± 14.5
    -2.0 ± 11.7
        Breast Symptoms: Change at C6D1 (n=63, 167)
    1.7 ± 16.0
    -2.0 ± 12.9
        Breast Symptoms: Change at C7D1 (n=57, 140)
    0.3 ± 12.6
    -3.2 ± 13.1
        Future Perspective: Baseline (n=152, 303)
    47.4 ± 31.5
    47.3 ± 29.6
        Future Perspective: Change at C2D1 (n=139, 281)
    3.4 ± 30.1
    6.8 ± 27.4
        Future Perspective: Change at C3D1 (n=111, 247)
    5.1 ± 29.5
    4.3 ± 30.5
        Future Perspective: Change at C4D1 (n=95, 220)
    6.0 ± 30.7
    7.0 ± 29.2
        Future Perspective: Change at C5D1 (n=72, 202)
    6.0 ± 30.3
    5.0 ± 26.8
        Future Perspective: Change at C6D1 (n=63, 167)
    6.9 ± 28.8
    9.0 ± 31.4
        Future Perspective: Change at C7D1 (n=57, 139)
    12.9 ± 29.4
    7.0 ± 30.2
        Sexual Enjoyment: Baseline (n=27, 61)
    51.9 ± 26.7
    62.8 ± 26.6
        Sexual Enjoyment: Change at C2D1 (n=17, 35)
    5.9 ± 21.2
    0.0 ± 18.1
        Sexual Enjoyment: Change at C3D1 (n=14, 26)
    4.8 ± 22.1
    1.3 ± 24.0
        Sexual Enjoyment: Change at C4D1 (n=8, 24)
    -8.3 ± 15.4
    4.2 ± 24.7
        Sexual Enjoyment: Change at C5D1 (n=7, 26)
    -4.8 ± 23.0
    2.6 ± 29.7
        Sexual Enjoyment: Change at C6D1 (n=5, 17)
    -6.7 ± 14.9
    -5.9 ± 24.3
        Sexual Enjoyment: Change at C7D1 (n=5, 14)
    -13.3 ± 29.8
    9.5 ± 20.4
        Sexual Functioning: Baseline (n=142, 291)
    89.6 ± 17.9
    89.9 ± 17.3
        Sexual Functioning: Change at C2D1 (n=126, 267)
    1.6 ± 11.0
    1.5 ± 14.2
        Sexual Functioning: Change at C3D1 (n=98, 235)
    1.4 ± 10.6
    1.8 ± 15.6
        Sexual Functioning: Change at C4D1 (n=86, 203)
    1.9 ± 15.4
    1.6 ± 13.9
        Sexual Functioning: Change at C5D1 (n=63, 186)
    -0.8 ± 20.6
    2.6 ± 15.1
        Sexual Functioning: Change at C6D1 (n=55, 156)
    2.4 ± 18.8
    2.7 ± 15.0
        Sexual Functioning: Change at C7D1 (n=49, 132)
    2.7 ± 18.1
    2.3 ± 15.7
        Systematic Therapy SEs: Baseline (n=152, 304)
    15.7 ± 14.2
    14.7 ± 12.0
        Systematic Therapy SEs:Change at C2D1 (n=140, 282)
    0.2 ± 11.4
    2.5 ± 11.0
        Systematic Therapy SEs:Change at C3D1 (n=112, 250)
    1.2 ± 14.4
    4.0 ± 13.6
        Systematic Therapy SEs:Change at C4D1 (n=95, 220)
    1.5 ± 13.2
    4.0 ± 13.3
        Systematic Therapy SEs:Change at C5D1 (n=72, 203)
    2.4 ± 13.8
    5.5 ± 14.1
        Systematic Therapy SEs:Change at C6D1 (n=63, 167)
    2.9 ± 15.2
    5.7 ± 15.6
        Systematic Therapy SEs:Change at C7D1 (n=57, 140)
    3.5 ± 16.7
    4.8 ± 15.0
        Upset by Hair Loss: Baseline (n=33, 63)
    23.2 ± 28.2
    27.0 ± 29.2
        Upset by Hair Loss: Change at C2D1 (n=14, 31)
    -11.9 ± 28.1
    -4.3 ± 22.3
        Upset by Hair Loss: Change at C3D1 (n=13, 29)
    -7.7 ± 30.9
    0.0 ± 26.7
        Upset by Hair Loss: Change at C4D1 (n=13, 27)
    2.6 ± 16.5
    0.0 ± 29.2
        Upset by Hair Loss: Change at C5D1 (n=8, 28)
    0.0 ± 25.2
    10.7 ± 27.3
        Upset by Hair Loss: Change at C6D1 (n=6, 26)
    11.1 ± 27.2
    16.7 ± 30.2
        Upset by Hair Loss: Change at C7D1 (n=8, 26)
    4.2 ± 11.8
    14.1 ± 32.9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Objective Response (PR plus CR), as Assessed Using RECIST v.1.1 at Final Analysis

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    End point title
    		 Percentage of Subjects with Objective Response (PR plus CR), as Assessed Using RECIST v.1.1 at Final Analysis
    End point description
    PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalisation of tumor marker levels (as applicable to non-target lesions). Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    134
    264
    Units: percentage of subjects
        number (confidence interval 95%)
    13.4 (8.2 to 20.2)
    31.1 (25.5 to 36.8)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 5.4

    Secondary: OS at Final Analysis

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    End point title
    		 OS at Final Analysis
    End point description
    OS was defined as the time from the date of randomisation to the date of death due to any cause. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point. 99999 represents that the upper limit of confidence interval was not estimable due to the low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From randomisation up to death from any cause (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    27.93 (24.38 to 99999)
    27.79 (24.25 to 33.35)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9974
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.33

    Secondary: Percentage of Subjects with Clinical Benefit, as Assessed According to RECIST v1.1 at Final Analysis

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    End point title
    		 Percentage of Subjects with Clinical Benefit, as Assessed According to RECIST v1.1 at Final Analysis
    End point description
    Clinical benefit:objective response (PR+CR),or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomisation.PR:at least a 30% decrease in sum of diameters of target lesions,taking as reference baseline sum of diameters.CR:disappearance of all target and non-target lesions and normalisation of tumor marker levels.Disease progression:at least a 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study,including baseline.In addition to relative increase of 20%,sum must also demonstrate absolute increase of at least 5 mm.For non-target lesions,disease progression:unequivocal progression of existing lesions.Appearance of one or more new lesions was also considered progression.Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline,regardless of whether they received any amount of study treatment.Number of subjects analysed is number of subjects with data available at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    134
    264
    Units: percentage of subjects
        number (confidence interval 95%)
    45.5 (37.2 to 54.3)
    59.5 (53.6 to 65.4)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 3

    Secondary: DOR as Assessed by Investigator Using RECIST v1.1 at Final Analysis ‌

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    End point title
    		 DOR as Assessed by Investigator Using RECIST v1.1 at Final Analysis ‌
    End point description
    DOR:time from first tumor assessment for objective response to first documented disease progression or death due to any cause, whichever occurred first. CR:disappearance of all target and non-target lesions and normalisation of tumor marker levels.PR:at least a 30% decrease in the sum of diameters of target lesions,taking as reference baseline sum of diameters. Disease progression:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline.For non-target lesions, disease progression:unequivocal progression of existing lesions.Appearance of one or more new lesions was also considered progression.Randomised subjects with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Number analysed:number of subjects with data available for analysis at given timepoint.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    18
    82
    Units: months
        median (confidence interval 95%)
    7.39 (4.67 to 23.95)
    8.97 (7.36 to 12.91)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8286
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 2.35

    Secondary: PFS as Assessed by BICR Using RECIST v1.1 at Final Analysis ‌

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    End point title
    		 PFS as Assessed by BICR Using RECIST v1.1 at Final Analysis ‌
    End point description
    PFS was defined as the time from randomisation to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Randomised subjects with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    176
    340
    Units: months
        median (confidence interval 95%)
    5.55 (3.68 to 9.30)
    9.20 (8.15 to 10.87)
    Statistical analysis title
    		 Taselisib+Fulvestrant vs Placebo+Fulvestrant
    Comparison groups
    Placebo+Fulvestrant v Taselisib+Fulvestrant
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0095
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 0.92

    Secondary: Percentage of Subjects with AEs at Final Analysis

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    End point title
    		 Percentage of Subjects with AEs at Final Analysis
    End point description
    An AE was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The safety-evaluable population included all randomised subjects who received at least one dose of taselisib or placebo or fulvestrant. Number of subjects analysed is the number of subjects with data available for analysis at given time point.
    End point type
    Secondary
    End point timeframe
    From randomisation up to approximately 6.2 years
    End point values
    		 Placebo+Fulvestrant Taselisib+Fulvestrant
    Number of subjects analysed
    213
    416
    Units: percentage of subjects
        number (not applicable)
    91.1
    97.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From randomization up to the end of study, approximately 6.2 years
    Adverse event reporting additional description
    The safety-evaluable population included all randomized participants who received at least one dose of taselisib, placebo or fulvestrant regardless of the PIK3CA-mutation status of their tumors with participants allocated to the treatment arm associated with the regimen actually received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Taselisib+Fulvestrant
    Reporting group description
    		 Subjects received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Reporting group title
    Placebo+Fulvestrant
    Reporting group description
    		 Subjects received taselisib-matching placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28‑day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

    Serious adverse events
    		 Taselisib+Fulvestrant Placebo+Fulvestrant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    154 / 416 (37.02%)
    23 / 213 (10.80%)
         number of deaths (all causes)
    197
    98
         number of deaths resulting from adverse events
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    HEPATOCELLULAR CARCINOMA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTRACRANIAL TUMOUR HAEMORRHAGE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (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 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SHOCK
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMBOLISM VENOUS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (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
    CHILLS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    3 / 416 (0.72%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHEST DISCOMFORT
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    2 / 416 (0.48%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASTHENIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    3 / 416 (0.72%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SWELLING FACE
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    3 / 416 (0.72%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Immune system disorders
    ANAPHYLACTIC SHOCK
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    INTERMENSTRUAL BLEEDING
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 416 (0.24%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 416 (0.24%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    10 / 416 (2.40%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    10 / 10
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 416 (0.24%)
    1 / 213 (0.47%)
         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
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    2 / 416 (0.48%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    HIP FRACTURE
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WRIST FRACTURE
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TOXICITY TO VARIOUS AGENTS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (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 / 416 (0.24%)
    0 / 213 (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
    2 / 416 (0.48%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         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 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    3 / 416 (0.72%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRIGEMINAL NEURALGIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOAESTHESIA
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL HAEMATOMA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FACIAL PARALYSIS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    1 / 416 (0.24%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    VITH NERVE PARALYSIS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         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
    2 / 416 (0.48%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    DYSPHAGIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (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
    4 / 416 (0.96%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STOMATITIS
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC ULCER
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    3 / 416 (0.72%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    16 / 416 (3.85%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    17 / 17
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTERITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    37 / 416 (8.89%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    36 / 40
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGEAL ULCER
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    4 / 416 (0.96%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ALCOHOLIC PANCREATITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPEPSIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATOTOXICITY
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TOXIC SKIN ERUPTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DRUG ERUPTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PRURITUS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (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
    4 / 416 (0.96%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URETEROLITHIASIS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COCCYDYNIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OSTEONECROSIS OF JAW
         subjects affected / exposed
    0 / 416 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RHABDOMYOLYSIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHRALGIA
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    ENTEROCOLITIS INFECTIOUS
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CYSTITIS ESCHERICHIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLERA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN INFECTION
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    5 / 416 (1.20%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    10 / 416 (2.40%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    4 / 10
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATYPICAL MYCOBACTERIAL PNEUMONIA
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA INFECTIOUS
         subjects affected / exposed
    3 / 416 (0.72%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPTIC ARTHRITIS STAPHYLOCOCCAL
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    APPENDICITIS PERFORATED
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    2 / 416 (0.48%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 416 (0.72%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA
         subjects affected / exposed
    7 / 416 (1.68%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    7 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    7 / 416 (1.68%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    5 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DECREASED APPETITE
         subjects affected / exposed
    1 / 416 (0.24%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    		 Taselisib+Fulvestrant Placebo+Fulvestrant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    396 / 416 (95.19%)
    183 / 213 (85.92%)
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    25 / 416 (6.01%)
    6 / 213 (2.82%)
         occurrences all number
    28
    7
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    15 / 416 (3.61%)
    12 / 213 (5.63%)
         occurrences all number
    17
    12
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    35 / 416 (8.41%)
    15 / 213 (7.04%)
         occurrences all number
    47
    19
    WEIGHT DECREASED
         subjects affected / exposed
    42 / 416 (10.10%)
    6 / 213 (2.82%)
         occurrences all number
    50
    6
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    36 / 416 (8.65%)
    9 / 213 (4.23%)
         occurrences all number
    47
    13
    Vascular disorders
    HOT FLUSH
         subjects affected / exposed
    24 / 416 (5.77%)
    27 / 213 (12.68%)
         occurrences all number
    26
    27
    HYPERTENSION
         subjects affected / exposed
    33 / 416 (7.93%)
    11 / 213 (5.16%)
         occurrences all number
    42
    16
    Nervous system disorders
    DYSGEUSIA
         subjects affected / exposed
    36 / 416 (8.65%)
    5 / 213 (2.35%)
         occurrences all number
    41
    5
    HEADACHE
         subjects affected / exposed
    88 / 416 (21.15%)
    27 / 213 (12.68%)
         occurrences all number
    122
    38
    DIZZINESS
         subjects affected / exposed
    46 / 416 (11.06%)
    18 / 213 (8.45%)
         occurrences all number
    58
    23
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    48 / 416 (11.54%)
    9 / 213 (4.23%)
         occurrences all number
    61
    10
    FATIGUE
         subjects affected / exposed
    105 / 416 (25.24%)
    40 / 213 (18.78%)
         occurrences all number
    134
    51
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    44 / 416 (10.58%)
    11 / 213 (5.16%)
         occurrences all number
    67
    15
    ASTHENIA
         subjects affected / exposed
    77 / 416 (18.51%)
    40 / 213 (18.78%)
         occurrences all number
    104
    65
    OEDEMA PERIPHERAL
         subjects affected / exposed
    19 / 416 (4.57%)
    11 / 213 (5.16%)
         occurrences all number
    25
    13
    Blood and lymphatic system disorders
    NEUTROPENIA
         subjects affected / exposed
    28 / 416 (6.73%)
    9 / 213 (4.23%)
         occurrences all number
    39
    12
    ANAEMIA
         subjects affected / exposed
    44 / 416 (10.58%)
    20 / 213 (9.39%)
         occurrences all number
    62
    23
    Gastrointestinal disorders
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    23 / 416 (5.53%)
    4 / 213 (1.88%)
         occurrences all number
    25
    4
    CONSTIPATION
         subjects affected / exposed
    32 / 416 (7.69%)
    32 / 213 (15.02%)
         occurrences all number
    36
    36
    VOMITING
         subjects affected / exposed
    86 / 416 (20.67%)
    25 / 213 (11.74%)
         occurrences all number
    116
    41
    DIARRHOEA
         subjects affected / exposed
    255 / 416 (61.30%)
    45 / 213 (21.13%)
         occurrences all number
    602
    76
    DRY MOUTH
         subjects affected / exposed
    55 / 416 (13.22%)
    18 / 213 (8.45%)
         occurrences all number
    62
    19
    STOMATITIS
         subjects affected / exposed
    87 / 416 (20.91%)
    8 / 213 (3.76%)
         occurrences all number
    139
    11
    NAUSEA
         subjects affected / exposed
    154 / 416 (37.02%)
    54 / 213 (25.35%)
         occurrences all number
    233
    71
    DYSPEPSIA
         subjects affected / exposed
    32 / 416 (7.69%)
    5 / 213 (2.35%)
         occurrences all number
    51
    5
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    31 / 416 (7.45%)
    8 / 213 (3.76%)
         occurrences all number
    35
    8
    ABDOMINAL PAIN
         subjects affected / exposed
    55 / 416 (13.22%)
    20 / 213 (9.39%)
         occurrences all number
    67
    25
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    50 / 416 (12.02%)
    17 / 213 (7.98%)
         occurrences all number
    53
    17
    COUGH
         subjects affected / exposed
    64 / 416 (15.38%)
    34 / 213 (15.96%)
         occurrences all number
    78
    41
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    80 / 416 (19.23%)
    17 / 213 (7.98%)
         occurrences all number
    116
    24
    DRY SKIN
         subjects affected / exposed
    37 / 416 (8.89%)
    10 / 213 (4.69%)
         occurrences all number
    40
    10
    PRURITUS
         subjects affected / exposed
    52 / 416 (12.50%)
    18 / 213 (8.45%)
         occurrences all number
    75
    28
    ALOPECIA
         subjects affected / exposed
    50 / 416 (12.02%)
    6 / 213 (2.82%)
         occurrences all number
    53
    6
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    37 / 416 (8.89%)
    18 / 213 (8.45%)
         occurrences all number
    40
    19
    Musculoskeletal and connective tissue disorders
    MUSCLE SPASMS
         subjects affected / exposed
    32 / 416 (7.69%)
    6 / 213 (2.82%)
         occurrences all number
    34
    8
    BACK PAIN
         subjects affected / exposed
    62 / 416 (14.90%)
    28 / 213 (13.15%)
         occurrences all number
    82
    32
    BONE PAIN
         subjects affected / exposed
    24 / 416 (5.77%)
    17 / 213 (7.98%)
         occurrences all number
    26
    19
    ARTHRALGIA
         subjects affected / exposed
    69 / 416 (16.59%)
    35 / 213 (16.43%)
         occurrences all number
    95
    50
    MYALGIA
         subjects affected / exposed
    36 / 416 (8.65%)
    14 / 213 (6.57%)
         occurrences all number
    42
    14
    PAIN IN EXTREMITY
         subjects affected / exposed
    33 / 416 (7.93%)
    19 / 213 (8.92%)
         occurrences all number
    42
    27
    Infections and infestations
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    33 / 416 (7.93%)
    11 / 213 (5.16%)
         occurrences all number
    41
    17
    URINARY TRACT INFECTION
         subjects affected / exposed
    38 / 416 (9.13%)
    9 / 213 (4.23%)
         occurrences all number
    50
    10
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA
         subjects affected / exposed
    166 / 416 (39.90%)
    21 / 213 (9.86%)
         occurrences all number
    233
    26
    HYPOKALAEMIA
         subjects affected / exposed
    31 / 416 (7.45%)
    2 / 213 (0.94%)
         occurrences all number
    37
    2
    DECREASED APPETITE
         subjects affected / exposed
    119 / 416 (28.61%)
    23 / 213 (10.80%)
         occurrences all number
    136
    25

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2015
    The changes in Protocol v2 were as follows: The study design section was updated. Now, all subjects who discontinued study treatment were followed for OS and subsequent anti-cancer therapies, not only those who discontinued study treatment due to disease progression. The text was also updated to clarify that only subjects who discontinued taselisib/placebo for toxicity could continue single agent fulvestrant at the discretion of the investigator while those who discontinued fulvestrant for an AE, albeit rare, should discuss continuation of single agent taselisib/placebo with the Medical Monitor. The biomarker section was updated to clarify the analysis of optional post-progression biopsies and sharing of the resulting molecular report with investigator who may then share the data with the subject (if the subject agreed). Subjects who discontinue study treatment for reasons other than disease progression will continue to undergo tumor assessments until progressive disease (PD), even if a subject initiates anti-cancer therapy subsequent to study drug discontinuation. An update was made to clarify corticosteroid treatment for Grade 3 diarrhoea or colitis. An update was made for clarification of the pneumonitis guidelines related to local clinical practice. A footnote was added to clarify for Grade 1 or 2 hyperglycemia that increases in anti-hyperglycemic medications only applied to subjects who initiated these after randomisation since subjects with diabetes requiring anti-hyperglycemic medications were not eligible. Updates were made to point to specific management guidelines for subjects who experienced changes in blood counts or showed signs of infections if deemed clinically appropriate by the investigator. An update was made regarding additional supporting data sponsor may request for certain AEs. A clarification was included to mention that the study used electronic patient-reported outcome (ePRO) devices and no paper questionnaires.
    15 Jan 2017
    The changes in Protocol v3 were as follows: The testing hierarchy of the secondary endpoints was changed to ORR first followed by OS after a statistically significant investigator-assessed PFS. OS was still formally tested if both investigator-assessed PFS and ORR reached their significance level. A secondary efficacy objective/outcome measure was added: BICR-assessed PFS, which was intended to show that there was no potential bias in the investigator-assessed PFS. CBR was added to the exploratory objectives. The possible addition of a China extension cohort was introduced. After the global enrollment closes, additional Chinese subjects may continue to be recruited into the China extension cohort. A total of up to 150 Chinese subjects with detectable PIK3CA-mutant tumors may be enrolled as part of the global study population and extension cohort combined. An inclusion criterion was added to define the subject population in the China extension cohort to be from the People’s Republic of China. Blinding criteria for study personnel on the basis of the results of the interim and final analyses for investigator-assessed PFS was added. Optional post-progression biopsies could still be obtained within approximately 14 days of the start of the new anti-cancer treatment as long as it was deemed safe by the investigator.
    15 Jan 2017
    Additional changes in Protocol v3 were as follows: Clarifications of AE management guidelines: For diarrhoea, dose resumption was distinguished for certain cases of infectious diarrhoea; For pneumonitis, infectious work-up was listed as a relevant investigation. An interim efficacy analysis of investigator-assessed PFS was added to enable an earlier assessment of efficacy that could provide subjects with PIK3CA-mutant tumors with earlier access to a potentially effective targeted therapy should the iDMC recommended stopping the study early on the basis of results from the interim analysis for investigator-assessed PFS and should the Sponsor decide to accept the recommendation and obtained regulatory approval. The analysis of CBR was clarified to be performed for subjects with PIK3CA-mutant tumors with measurable disease at baseline as well as regardless of measurable disease at baseline. A time-to-deterioration analysis was included as one of the PRO to assess if there was a difference between the treatment arms.
    24 Jun 2018
    The changes in Protocol v4 were as follows: Background and Safety sections were updated with new taselisib adverse drug reactions detected in the primary PFS analysis and with management guidelines for infection. After approximately the end of August 2018, tumor assessments may be conducted per local standard of care because sufficient data have been gathered for these assessments. These include: tumor assessments for subjects who are discontinued from study treatment for reasons other than disease progression and tumor assessments 46 weeks after disease progression, all patient-reported outcomes (PROs), survival and subsequent anti-cancer therapies after study treatment discontinuation, Eastern Cooperative Oncology Group (ECOG) Performance Status, optional post-progression core tumor biopsy and Roche Clinical Repository (RCR) blood samples, plasma samples for pharmacokinetic (PK) and exploratory research, blood samples for next-generation sequencing (NGS) and pharmacogenetic assessment. The independent Data Monitoring Committee (iDMC) will only oversee safety monitoring until the primary PFS analysis has been completed and the Sponsor is unblinded. The end of the global study will be when the last patient, last visit (LPLV) has occurred or safety follow-up is received from the last patient (28 days after the last dose of study drug), whichever occurs later, or when the Sponsor decides to stop the study.
    24 Jun 2018
    Additional changes in Protocol v4 were as follows: After approximately the end of August 2018: Unblinding is permitted at the discretion of the investigator or Sponsor because the primary PFS analysis will have been competed, and blinding is no longer required; the list of prohibited therapies requiring Medical Monitor approval to initiate will be reduced, because the primary PFS analysis has been completed and these restrictions are no longer required. Adverse event follow-up will not be done after a subject is no longer being followed for survival because subjects will have been withdrawn from the study at that point. OS follow-up has been limited to one additional analysis because sufficient data have been gathered for this assessment. This additional OS analysis coincides with the originally planned second OS interim analysis.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    29 Jun 2021
    The Sponsor discontinued the manufacturing and development of taselisib due to modest clinical benefit and limited tolerability.
    -

    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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