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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Avelumab in Combination With Chemotherapy Followed by Maintenance Therapy of Avelumab in Combination With the Poly (Adenosine Diphosphate [ADP]-Ribose) Polymerase (PARP) Inhibitor Talazoparib in subjects With Previously Untreated Advanced Ovarian Cancer (JAVELIN Ovarian PARP 100)

    Summary
    EudraCT number
    2017-004456-30
    Trial protocol
    SK   CZ   HU   BE   GB   EE   HR   IT  
    Global end of trial date
    22 Dec 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Dec 2022
    First version publication date
    23 Dec 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B9991030
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03642132
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer Inc. 
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center , Pfizer Inc. , +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc. , +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Dec 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Dec 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Dec 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To demonstrate that avelumab in combination with platinum-based chemotherapy followed by avelumab plus talazoparib maintenance is superior to platinum based chemotherapy plus bevacizumab followed by bevacizumab maintenance in prolonging progressive-free survival(PFS) in subjects with advanced ovarian cancer with defects in DNA damage repair (DDR+).
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Jul 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    United States: 53
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Russian Federation: 2
    Worldwide total number of subjects
    79
    EEA total number of subjects
    12
    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)
    49
    From 65 to 84 years
    30
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. As only 11% projected enrollment was met at the time of enrollment stop, the original study endpoints are no longer applicable and/or feasible; only the Safety, PK and Immunogenicity Analysis were done and these data are included in this report.

    Pre-assignment
    Screening details
    A total of 104 subjects were screened. Seventy-nine subjects completed screening and were randomized in the study prior to study discontinuation. Seventy-six subjects received study treatment across the 3 arms

    Period 1
    Period 1 title
    Chemotherapy Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.
    Arm type
    Experimental

    Investigational medicinal product name
    Avelumab (MSB0010718C) Solution for Infusion, 20 mg/mL (10 mL/vial)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects reveived Avelumab 800 mg administered intravenously on Day 1 of each 3-week cycle for 6 cycles.

    Arm title
    Chemotherapy -> Talazoparib
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    Bevacizumab solution for intravenous infusion 400 mg/16 mL vial (Avastin)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6.

    Number of subjects in period 1
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Started
    32
    13
    34
    Completed
    19
    8
    27
    Not completed
    13
    5
    7
         Consent withdrawn by subject
    7
    3
    1
         Adverse event, non-fatal
    1
    1
    -
         Study terminated by sponsor
    -
    -
    3
         Unspecified
    1
    -
    2
         Progressive disease
    -
    -
    1
         Physician's decision
    4
    1
    -
    Period 2
    Period 2 title
    Maintenance Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.
    Arm type
    Experimental

    Investigational medicinal product name
    Avelumab (MSB0010718C) Solution for Infusion, 20 mg/mL (10 mL/vial)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects reveived Avelumab 800 mg administered intravenously on Days 1, 15 and 29 of each 6-week cycle.

    Investigational medicinal product name
    Talazoparib 1mg Bottle 30 ct. (MDV 3800 Capsules)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects reveived talazoparib 0.75 mg self-administered orally once per day.

    Arm title
    Chemotherapy -> Talazoparib
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib 0.25 mg Bottle 30 ct. (MDV3800 Capsules)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.

    Arm title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Arm description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    Bevacizumab solution for intravenous infusion 400 mg/16 mL vial (Avastin)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Bevacizumab 15 mg/kg administered intravenously on Days 1 and 22 of each 6-week cycle.

    Number of subjects in period 2 [1]
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Started
    18
    9
    23
    Completed
    5
    1
    9
    Not completed
    13
    8
    14
         Consent withdrawn by subject
    1
    1
    2
         Adverse event, non-fatal
    1
    2
    -
         Non-compliance with study drug
    -
    -
    1
         Unspecified
    -
    -
    3
         Progressive disease
    9
    3
    6
         Physician's decision
    2
    2
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number of subjects starting the period is accurate as specified

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.

    Reporting group title
    Chemotherapy -> Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.

    Reporting group title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.

    Reporting group values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab Total
    Number of subjects
    32 13 34 79
    Age Categorical
    Units: Subjects
        < 65 years
    21 8 20 49
        65 =< 75 years
    7 4 9 20
        75 =< 85 years
    4 1 5 10
        >= 85 years
    0 0 0 0
        Not Reported
    0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    61.38 ( 11.32 ) 58.46 ( 12.67 ) 63.29 ( 9.83 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    32 13 34 79
        Male
    0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        Blank or African American
    0 0 1 1
        American Indian or Alaska Native
    0 0 1 1
        Asian
    2 3 7 12
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        White
    29 10 24 63
        Other
    1 0 1 2
        Unknown
    0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    6 1 5 12
        Not Hispanic or Latino
    26 11 27 64
        Unknown or Not Reported
    0 1 2 3

    End points

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    End points reporting groups
    Reporting group title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.

    Reporting group title
    Chemotherapy -> Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.

    Reporting group title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
    Reporting group title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.

    Reporting group title
    Chemotherapy -> Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.

    Reporting group title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.

    Primary: Progression-Free Survival (Subjects with newly diagnosed advanced ovarian cancer with defects in DDR+)

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    End point title
    Progression-Free Survival (Subjects with newly diagnosed advanced ovarian cancer with defects in DDR+) [1]
    End point description
    PFS was defined as the time from randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. The analysis population included all randomized subjects. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Primary
    End point timeframe
    At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by Blinded Independent Central Review (BICR) regardless of initiation of new anti-cancer therapy
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [2] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [3] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [4] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment-Emergent Adverse Events (On-Treatment Period)

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    End point title
    Number of Subjects with Treatment-Emergent Adverse Events (On-Treatment Period)
    End point description
    An adverse event (AE( was any untoward medical occurrence in a study subject administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event was any untoward medical occurrence at any dose that resulted in death, was lifethreatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly/birth defect or considered to be an important medical event. An AE was considered TEAE if the event occurred during the on-treatment period On-treatment period was defined as the time from the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day. The analysis pupulation included all randomized subjects who received at least 1 dose of study drug (avelumab, talazoparib, bevacizumab, carboplatin, paclitaxel).
    End point type
    Secondary
    End point timeframe
    From the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day (maximum up to 3.5 years approximately)
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    29
    13
    34
    Units: Subjects
        Subjects with TEAEs
    29
    13
    34
    No statistical analyses for this end point

    Secondary: Number of Subjects With ADA Against Avelumab by Never and Ever Positive Status

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    End point title
    Number of Subjects With ADA Against Avelumab by Never and Ever Positive Status [5]
    End point description
    Predose Anti‑drug antibodies (ADA) samples were collected within 2 hours prior to avelumab dosing and drawn from the contralateral arm of the avelumab infusion. The analysis population included subjects in Arm A (Chemotherapy +Avelumab -> Avelumab + Talazoparib) only, who had at least 1 ADA sample collected. Only avelumab containing Arm (Arm A) was included as the analysis was against avelumab.
    End point type
    Secondary
    End point timeframe
    Day 1 pre-dose of Cycles 1, 2, 3, and 4 in the chemotherapy period and Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period. A sample was also collected at the end of treatment/withdrawal.
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Number of subjects analysed
    29
    Units: Subjects
        ADA never-positive
    17
        ADA ever-positive
    12
    No statistical analyses for this end point

    Secondary: Pre-dose/trough concentration (Ctrough) for avelumab (chemotherapy period)

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    End point title
    Pre-dose/trough concentration (Ctrough) for avelumab (chemotherapy period) [6]
    End point description
    Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data. The analysis population included subjects who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab. concentration..Here, "Number of Subjects analyzed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Number of subjects analysed
    29
    Units: mcg/mL
    median (full range (min-max))
        Cycle 1 Day 1 0H
    0.000 (0.00 to 5.61)
        Cycle 2 Day 1 0H
    4.370 (0.00 to 10.8)
        Cycle 3 Day 1 0H
    6.100 (0.00 to 20.9)
        Cycle 4 Day 1 0H
    10.00 (0.686 to 16.1)
    No statistical analyses for this end point

    Secondary: Pre-dose/trough concentration (Ctrough) for avelumab (maintenance period)

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    End point title
    Pre-dose/trough concentration (Ctrough) for avelumab (maintenance period) [7]
    End point description
    Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data.The analysis population included subjects who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab. concentration..Here, "Number of Subjects analyzed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period (1 cycle = 6 weeks) and at the end of treatment.
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Number of subjects analysed
    29
    Units: mcg/mL
    median (full range (min-max))
        Cycle 1 Day 1 0H
    3.470 (0.00 to 25.7)
        Cycle 1 Day 29 0H
    41.60 (19.5 to 78.0)
        Cycle 2 Day 1 0H
    33.90 (25.7 to 63.6)
        Cycle 4 Day 1 0H
    28.60 (23.3 to 41.0)
        Cycle 6 Day 1 0H
    20.6 (20.6 to 20.6)
    No statistical analyses for this end point

    Secondary: Cmax for avelumab (chemotherapy period)

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    End point title
    Cmax for avelumab (chemotherapy period) [8]
    End point description
    Cmax was defined as maximum observed plasma concentration and it was observed directly from data.The analysis population included subjects who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab. concentration..Here, "Number of Subjects analyzed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Number of subjects analysed
    29
    Units: mcg/mL
    median (full range (min-max))
        Cycle 1 Day 1 1H/End of infusion(EOI)
    218.0 (132 to 318)
        Cycle 2 Day 1 1H/End of infusion(EOI)
    222.5 (29.8 to 319)
        Cycle 3 Day 1 1H/End of infusion(EOI)
    253.0 (157 to 349)
        Cycle 4 Day 1 1H/End of infusion(EOI)
    243.0 (139 to 343)
    No statistical analyses for this end point

    Secondary: Cmax for avelumab (maintenance period)

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    End point title
    Cmax for avelumab (maintenance period) [9]
    End point description
    Cmax was defined as maximum observed plasma concentration and it was observed directly from data.The analysis population included subjects who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab. concentration..Here, "Number of Subjects analyzed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period (1 cycle = 6 weeks). A sample was also collected at the end of treatment/withdrawal.
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Number of subjects analysed
    29
    Units: mcg/mL
    median (full range (min-max))
        Cycle 1 Day 1 1H/End of infusion(EOI)
    227.0 (154 to 282)
        Cycle 1 Day 29 1H/End of infusion(EOI)
    279.0 (190 to 485)
        Cycle 2 Day 1 1H/End of infusion(EOI)
    222.0 (158 to 289)
        Cycle 4 Day 1 1H/End of infusion(EOI)
    225.0 (224 to 226)
        Cycle 6 Day 1 1H/End of infusion(EOI)
    219.0 (219 to 219)
    No statistical analyses for this end point

    Secondary: Ctrough for talazoprib (maintenance period)

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    End point title
    Ctrough for talazoprib (maintenance period) [10]
    End point description
    Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data.The analysis population included subjects who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab. concentration..Here, "Number of Subjects analyzed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 1, 15 and 29 of Cycle 1
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point is reporting statistics for the arms specified.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib
    Number of subjects analysed
    16
    8
    Units: pg/mL
    median (full range (min-max))
        Cycle 1 Day 1
    0.000 (0.00 to 0.00)
    0.000 (0.00 to 0.00)
        Cycel 1 Day 15
    2425 (1920 to 2930)
    1343 (865 to 1820)
        Cycel 1 Day 29
    2500 (2060 to 6470)
    1950 (660 to 3290)
    No statistical analyses for this end point

    Secondary: Overall Survival (subjects of both DDR+ and unselected DDR status)

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    End point title
    Overall Survival (subjects of both DDR+ and unselected DDR status)
    End point description
    OS was defined as the time from the date of randomization to the date of death due to any cause.As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    From 9 weeks up to 144 months
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [11]
    0 [12]
    0 [13]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [11] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [12] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [13] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (subjects of unselected DDR status)

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    End point title
    Progression-Free Survival (subjects of unselected DDR status)
    End point description
    PFS was defined as the time from the date of randomization to the date of the first documentation of PD or death due to any cause, whichever occured first. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by BICR regardless of initiation of new anti-cancer therapy
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [14] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [15] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [16] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (subjects of both DDR+ and unselected DDR status)

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    End point title
    Progression-Free Survival (subjects of both DDR+ and unselected DDR status)
    End point description
    PFS was defined as the time from randomization to the date of the first documentation of objective progressive disease(PD) or death due to any cause, whichever occurred first. Subjects was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by BICR regardless of initiation of new anti-cancer therapy
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [17]
    0 [18]
    0 [19]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [17] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [18] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [19] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival on next-line therapy (subjects of both DDR+ and unselected DDR status)

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    End point title
    Progression-Free Survival on next-line therapy (subjects of both DDR+ and unselected DDR status)
    End point description
    Progression-free survival on next-line therapy (PFS2) was defined as time from the date of randomization to the start of second subsequent treatment after first documentation of PD, or death from any cause, whichever occurred first. Subjects was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    From screening until the subject had objective PD on or prior to start of next-line anti-cancer treatment, and started a second subsequent anti-cancer treatment or the subject died.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [20]
    0 [21]
    0 [22]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [20] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [21] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [22] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score

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    End point title
    Functional Assessment of Ovarian Symptom Index-18 (FOSI-18) Score
    End point description
    NFOSI-18 was an ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. It was specifically designed to be a stand-alone instrument to measure disease-related symptoms, treatment side effects and function/well-being in subjects with ovarian cancer. The NFOSI-18 has several subscales: disease-related symptoms physical subscale (9 items), disease-related symptoms emotional subscale(1 item), treatment-related side effect subscale (5 items) and functional well-being (3 items). A score of “0” was a severely symptomatic subject and the highest possible score was an asymptomatic subject. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [23]
    0 [24]
    0 [25]
    Units: units on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [23] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [24] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [25] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: PFS per Gynecological Cancer Intergroup criteria (subjects of both DDR+ and unselected DDR status)

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    End point title
    PFS per Gynecological Cancer Intergroup criteria (subjects of both DDR+ and unselected DDR status)
    End point description
    PFS based on investigator assessment per Gynecological Cancer Intergroup criteria (GCIG) would be assessed incorporating both Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and CA 125. Subjects was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    From screening until death, end of study, or subject withdrawal of consent, whichever occurred first.
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [26]
    0 [27]
    0 [28]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [26] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [27] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [28] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline

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    End point title
    Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor and Immune Cells as Assessed by Immunohistochemistry (IHC) at Baseline
    End point description
    The number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest that were defined by tumor cell morphology and the presence or absence of inflammatory cells. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [29]
    0 [30]
    0 [31]
    Units: Percentage of cells staining postive
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    Notes
    [29] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [30] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [31] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: EuroQol Group 5‑Dimension 5‑Level (EQ‑5D‑5L) Score

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    End point title
    EuroQol Group 5‑Dimension 5‑Level (EQ‑5D‑5L) Score
    End point description
    The EuroQol EQ-5D-5L was a 6 item subject-completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EQ-5D-5L, a Health State Profile which had individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a Visual Analogue Scale (VAS) in which subjects rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Overall index scores ranged from 0 to 1, with low scores representing a higher level of dysfunction. As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [32]
    0 [33]
    0 [34]
    Units: units on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [32] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [33] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [34] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Secondary: Number of subjects with mutations in key oncogenes at baseline

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    End point title
    Number of subjects with mutations in key oncogenes at baseline
    End point description
    Determination/estimation of the frequency of mutations (total and non-synonymous) present in baseline tumor derived nucleic acid samples and in baseline circulating tumor DNA. A total of 104 subjects were screened and 79 subjects completed screening and randomized in the study before study discontinuation, and 76 subjects were treated across 3 treatment arms. As only 11% projected enrollment was met when enrollment stopped, the original study endpoints are no longer applicable and/or feasible.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy -> Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab
    Number of subjects analysed
    0 [35]
    0 [36]
    0 [37]
    Units: Subjects
    Notes
    [35] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [36] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    [37] - Data for this endpoint was not reported as no formal efficacy analyses performed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the signing of Informed consent (IC) up to 90 calendar days after the last administration of the investigational product (maximum of 3.5 years). AEs were summarized based on the on-treatment period unless otherwise specified.
    Adverse event reporting additional description
    Both non serious AEs and SAEs were recorded on the case report form.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Chemotherapy +Avelumab -> Avelumab + Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3 week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.

    Reporting group title
    Chemotherapy + Bevacizumab -> Bevacizumab
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with Bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant subjects, and for neoadjuvant subjects, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, subjects received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.

    Reporting group title
    Chemotherapy -> Talazoparib
    Reporting group description
    In chemotherapy period, subjects received paclitaxel 175 mg/m^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, subjects received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.

    Serious adverse events
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab Chemotherapy -> Talazoparib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 29 (31.03%)
    15 / 34 (44.12%)
    4 / 13 (30.77%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Incarcerated hernia
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Muscle strain
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Chemotherapy +Avelumab -> Avelumab + Talazoparib Chemotherapy + Bevacizumab -> Bevacizumab Chemotherapy -> Talazoparib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 29 (100.00%)
    34 / 34 (100.00%)
    13 / 13 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    1 / 13 (7.69%)
         occurrences all number
    2
    4
    3
    Deep vein thrombosis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Hot flush
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    2 / 13 (15.38%)
         occurrences all number
    3
    2
    2
    Hypertension
         subjects affected / exposed
    0 / 29 (0.00%)
    11 / 34 (32.35%)
    1 / 13 (7.69%)
         occurrences all number
    0
    21
    1
    Hypotension
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Fatigue
         subjects affected / exposed
    14 / 29 (48.28%)
    9 / 34 (26.47%)
    6 / 13 (46.15%)
         occurrences all number
    17
    14
    13
    Asthenia
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    3 / 13 (23.08%)
         occurrences all number
    5
    5
    3
    Adverse drug reaction
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    4
    0
    Pain
         subjects affected / exposed
    5 / 29 (17.24%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    5
    2
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 29 (0.00%)
    4 / 34 (11.76%)
    1 / 13 (7.69%)
         occurrences all number
    0
    5
    1
    Malaise
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Influenza like illness
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    5 / 29 (17.24%)
    4 / 34 (11.76%)
    1 / 13 (7.69%)
         occurrences all number
    7
    4
    1
    Temperature intolerance
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 34 (8.82%)
    0 / 13 (0.00%)
         occurrences all number
    0
    3
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Seasonal allergy
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Reproductive system and breast disorders
    Vaginal discharge
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    3
    0
    Vaginal haemorrhage
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    Vulvovaginal burning sensation
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Vulvovaginal pain
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 29 (20.69%)
    5 / 34 (14.71%)
    3 / 13 (23.08%)
         occurrences all number
    8
    7
    3
    Dyspnoea
         subjects affected / exposed
    7 / 29 (24.14%)
    5 / 34 (14.71%)
    3 / 13 (23.08%)
         occurrences all number
    10
    8
    4
    Oropharyngeal pain
         subjects affected / exposed
    1 / 29 (3.45%)
    4 / 34 (11.76%)
    0 / 13 (0.00%)
         occurrences all number
    1
    4
    0
    Epistaxis
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    0 / 13 (0.00%)
         occurrences all number
    2
    3
    0
    Pleural effusion
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 29 (17.24%)
    5 / 34 (14.71%)
    2 / 13 (15.38%)
         occurrences all number
    5
    5
    2
    Anxiety
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    2
    Depression
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Mental status changes
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 34 (8.82%)
    1 / 13 (7.69%)
         occurrences all number
    1
    6
    1
    Platelet count decreased
         subjects affected / exposed
    3 / 29 (10.34%)
    3 / 34 (8.82%)
    0 / 13 (0.00%)
         occurrences all number
    10
    9
    0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    3 / 13 (23.08%)
         occurrences all number
    9
    6
    12
    Lipase increased
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Blood corticotrophin increased
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    2 / 13 (15.38%)
         occurrences all number
    0
    5
    2
    White blood cell count decreased
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    4
    1
    8
    Weight increased
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    Fall
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Foot fracture
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    2 / 13 (15.38%)
         occurrences all number
    4
    3
    2
    Vulvovaginal injury
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    3
    2
    0
    Atrial fibrillation
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Nervous system disorders
    Cognitive disorder
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    8 / 29 (27.59%)
    12 / 34 (35.29%)
    1 / 13 (7.69%)
         occurrences all number
    9
    15
    2
    Paraesthesia
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 34 (8.82%)
    1 / 13 (7.69%)
         occurrences all number
    1
    4
    1
    Hypoaesthesia
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    2 / 13 (15.38%)
         occurrences all number
    5
    2
    2
    Dizziness
         subjects affected / exposed
    8 / 29 (27.59%)
    5 / 34 (14.71%)
    4 / 13 (30.77%)
         occurrences all number
    11
    5
    4
    Dysgeusia
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    0
    1
    Headache
         subjects affected / exposed
    5 / 29 (17.24%)
    10 / 34 (29.41%)
    2 / 13 (15.38%)
         occurrences all number
    5
    10
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 29 (10.34%)
    3 / 34 (8.82%)
    3 / 13 (23.08%)
         occurrences all number
    3
    3
    6
    Taste disorder
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    1
    Restless legs syndrome
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    2 / 29 (6.90%)
    4 / 34 (11.76%)
    1 / 13 (7.69%)
         occurrences all number
    3
    22
    4
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Anaemia
         subjects affected / exposed
    12 / 29 (41.38%)
    14 / 34 (41.18%)
    3 / 13 (23.08%)
         occurrences all number
    25
    22
    17
    Neutropenia
         subjects affected / exposed
    12 / 29 (41.38%)
    14 / 34 (41.18%)
    5 / 13 (38.46%)
         occurrences all number
    38
    41
    10
    Splenomegaly
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    8 / 29 (27.59%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    23
    7
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Visual field defect
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    4 / 29 (13.79%)
    4 / 34 (11.76%)
    0 / 13 (0.00%)
         occurrences all number
    4
    7
    0
    Abdominal discomfort
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    1
    Abdominal pain
         subjects affected / exposed
    8 / 29 (27.59%)
    7 / 34 (20.59%)
    3 / 13 (23.08%)
         occurrences all number
    10
    9
    3
    Diarrhoea
         subjects affected / exposed
    11 / 29 (37.93%)
    11 / 34 (32.35%)
    3 / 13 (23.08%)
         occurrences all number
    11
    21
    3
    Constipation
         subjects affected / exposed
    9 / 29 (31.03%)
    12 / 34 (35.29%)
    2 / 13 (15.38%)
         occurrences all number
    11
    4
    3
    Abdominal pain upper
         subjects affected / exposed
    4 / 29 (13.79%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    5
    1
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    2
    Dry mouth
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Nausea
         subjects affected / exposed
    12 / 29 (41.38%)
    14 / 34 (41.18%)
    3 / 13 (23.08%)
         occurrences all number
    22
    16
    6
    Gingival bleeding
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Flatulence
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    3
    2
    0
    Dysphagia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    2 / 13 (15.38%)
         occurrences all number
    4
    1
    2
    Oral pain
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Stomatitis
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    4
    4
    4
    Vomiting
         subjects affected / exposed
    4 / 29 (13.79%)
    7 / 34 (20.59%)
    2 / 13 (15.38%)
         occurrences all number
    4
    11
    2
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    12 / 29 (41.38%)
    10 / 34 (29.41%)
    7 / 13 (53.85%)
         occurrences all number
    13
    11
    8
    Dry skin
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Erythema
         subjects affected / exposed
    3 / 29 (10.34%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    3
    0
    1
    Pruritus
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    0 / 13 (0.00%)
         occurrences all number
    2
    4
    0
    Night sweats
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Rash
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    5
    3
    3
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Proteinuria
         subjects affected / exposed
    0 / 29 (0.00%)
    11 / 34 (32.35%)
    0 / 13 (0.00%)
         occurrences all number
    0
    36
    0
    Dysuria
         subjects affected / exposed
    5 / 29 (17.24%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    5
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 29 (37.93%)
    11 / 34 (32.35%)
    4 / 13 (30.77%)
         occurrences all number
    16
    13
    7
    Myalgia
         subjects affected / exposed
    8 / 29 (27.59%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    14
    7
    2
    Pain in extremity
         subjects affected / exposed
    2 / 29 (6.90%)
    5 / 34 (14.71%)
    1 / 13 (7.69%)
         occurrences all number
    2
    7
    1
    Muscle spasms
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Flank pain
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Bone pain
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Back pain
         subjects affected / exposed
    4 / 29 (13.79%)
    5 / 34 (14.71%)
    1 / 13 (7.69%)
         occurrences all number
    6
    8
    1
    Infections and infestations
    Folliculitis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Fungal infection
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    1
    Pneumonia
         subjects affected / exposed
    5 / 29 (17.24%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    5
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 34 (5.88%)
    1 / 13 (7.69%)
         occurrences all number
    3
    2
    1
    Sinusitis
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Tooth abscess
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 34 (2.94%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    1
    Urinary tract infection
         subjects affected / exposed
    4 / 29 (13.79%)
    7 / 34 (20.59%)
    1 / 13 (7.69%)
         occurrences all number
    7
    11
    1
    Vaginal infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 34 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 29 (10.34%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    3
    3
    2
    Dehydration
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 34 (8.82%)
    2 / 13 (15.38%)
         occurrences all number
    2
    3
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 34 (5.88%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Hypokalaemia
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 34 (8.82%)
    1 / 13 (7.69%)
         occurrences all number
    8
    4
    1
    Hypocalcaemia
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    2 / 29 (6.90%)
    5 / 34 (14.71%)
    1 / 13 (7.69%)
         occurrences all number
    2
    12
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 29 (0.00%)
    5 / 34 (14.71%)
    0 / 13 (0.00%)
         occurrences all number
    0
    7
    0
    Vitamin D deficiency
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 34 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Jun 2019
    The JAVELIN Ovarian 100 study (B9991010) was stopped due to futility of efficacy at a planned interim analysis, and therefore, the Sponsor decided to stop enrollment in the JAVELIN Ovarian PARP 100 study (B9991030). On 19 March 2019, a Dear Investigatior Letter was issued to notify the investigational sites that no new subjects could be screened or randomized. Subjects who remain in the study will continue receiving investigational products according to their randomized treatment assignment and will be monitored for appropriate safety assessments until treatment discontinuation. The purpose of protocol amendment 2 was to reduce study-specific procedure assessments (ie, efficacy, physical examination, electrocardiogram, ePROs and tumor assessments, PK and Biomarkers) for the ongoing subjects. The original schedule of activities(SOA) was replaced by a new SOA.The study objectives and endpoints in Section 2 were no longer applicable and/or feasible. The below assessments in section (Section 7) including Pharmacokinetic (Avelumab and Talazoparib); immunogenicity; Biomarker and Pharmacodynamic; Tumor Tissue Sample; Banked Biospecimens; Tumor Response Assessments including scans and Subject Reported Outcomes were no longer collected. A clarification was also included in the Data Analysis/Statistical Methods section(Section 9) to make the analysis fit for purpose.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    As only 11% projected enrollment was met prior to the study discontinuation, the original study endpoints are no longer applicable and/or feasible, only the Safety, PK and Immunogenicity Analysis were done and these data are included in this report.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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